Guidelines for Large-Scale Sequence-Based Complex Trait Association Studies: Lessons Learned from the NHLBI Exome Sequencing Project
Massively parallel whole-genome sequencing (WGS) data have ushered in a new era in human genetics. These data are now being used to understand the role of rare variants in complex traits and to advance the goals of precision medicine. The technological and computing advances that have enabled us to...
Saved in:
| Published in | American journal of human genetics Vol. 99; no. 4; pp. 791 - 801 |
|---|---|
| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
06.10.2016
Cell Press Elsevier |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0002-9297 1537-6605 1537-6605 |
| DOI | 10.1016/j.ajhg.2016.08.012 |
Cover
| Abstract | Massively parallel whole-genome sequencing (WGS) data have ushered in a new era in human genetics. These data are now being used to understand the role of rare variants in complex traits and to advance the goals of precision medicine. The technological and computing advances that have enabled us to generate WGS data on thousands of individuals have also outpaced our ability to perform analyses in scientifically and statistically rigorous and thoughtful ways. The past several years have witnessed the application of whole-exome sequencing (WES) to complex traits and diseases. From our analysis of NHLBI Exome Sequencing Project (ESP) data, not only have a number of important disease and complex trait association findings emerged, but our collective experience offers some valuable lessons for WGS initiatives. These include caveats associated with generating automated pipelines for quality control and analysis of rare variants; the importance of studying minority populations; sample size requirements and efficient study designs for identifying rare-variant associations; and the significance of incidental findings in population-based genetic research. With the ESP as an example, we offer guidance and a framework on how to conduct a large-scale association study in the era of WGS. |
|---|---|
| AbstractList | Massively parallel whole-genome sequencing (WGS) data have ushered in a new era in human genetics. These data are now being used to understand the role of rare variants in complex traits and to advance the goals of precision medicine. The technological and computing advances that have enabled us to generate WGS data on thousands of individuals have also outpaced our ability to perform analyses in scientifically and statistically rigorous and thoughtful ways. The past several years have witnessed the application of whole-exome sequencing (WES) to complex traits and diseases. From our analysis of NHLBI Exome Sequencing Project (ESP) data, not only have a number of important disease and complex trait association findings emerged, but our collective experience offers some valuable lessons for WGS initiatives. These include caveats associated with generating automated pipelines for quality control and analysis of rare variants; the importance of studying minority populations; sample size requirements and efficient study designs for identifying rare-variant associations; and the significance of incidental findings in population-based genetic research. With the ESP as an example, we offer guidance and a framework on how to conduct a large-scale association study in the era of WGS.Massively parallel whole-genome sequencing (WGS) data have ushered in a new era in human genetics. These data are now being used to understand the role of rare variants in complex traits and to advance the goals of precision medicine. The technological and computing advances that have enabled us to generate WGS data on thousands of individuals have also outpaced our ability to perform analyses in scientifically and statistically rigorous and thoughtful ways. The past several years have witnessed the application of whole-exome sequencing (WES) to complex traits and diseases. From our analysis of NHLBI Exome Sequencing Project (ESP) data, not only have a number of important disease and complex trait association findings emerged, but our collective experience offers some valuable lessons for WGS initiatives. These include caveats associated with generating automated pipelines for quality control and analysis of rare variants; the importance of studying minority populations; sample size requirements and efficient study designs for identifying rare-variant associations; and the significance of incidental findings in population-based genetic research. With the ESP as an example, we offer guidance and a framework on how to conduct a large-scale association study in the era of WGS. Massively parallel whole-genome sequencing (WGS) data have ushered in a new era in human genetics. These data are now being used to understand the role of rare variants in complex traits and to advance the goals of precision medicine. The technological and computing advances that have enabled us to generate WGS data on thousands of individuals have also outpaced our ability to perform analyses in scientifically and statistically rigorous and thoughtful ways. The past several years have witnessed the application of whole-exome sequencing (WES) to complex traits and diseases. From our analysis of NHLBI Exome Sequencing Project (ESP) data, not only have a number of important disease and complex trait association findings emerged, but our collective experience offers some valuable lessons for WGS initiatives. These include caveats associated with generating automated pipelines for quality control and analysis of rare variants; the importance of studying minority populations; sample size requirements and efficient study designs for identifying rare-variant associations; and the significance of incidental findings in population-based genetic research. With the ESP as an example, we offer guidance and a framework on how to conduct a large-scale association study in the era of WGS. |
| Author | Auer, Paul L. Abecasis, Goncalo R. Bamshad, Michael J. Rich, Stephen S. Nickerson, Deborah A. Leal, Suzanne M. Tracy, Russell P. Reiner, Alex P. Wang, Gao Kang, Hyun Min Altshuler, David |
| AuthorAffiliation | 1 Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, WI 53205, USA 10 Department of Pediatrics, University of Washington, Seattle, WA 98195, USA 12 Department of Biochemistry, University of Vermont, Burlington, VT 05405, USA 9 Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA 11 Department of Pathology, University of Vermont, Colchester, VT 05405, USA 8 Vertex Pharmaceuticals, Boston, MA 02210, USA 2 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA 6 Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA 3 Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA 98195, USA 4 Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA 5 Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA 7 Broad Institute of MIT and Harvard, Cambridge, MA 02142, |
| AuthorAffiliation_xml | – name: 5 Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA – name: 6 Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA – name: 7 Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA – name: 2 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA – name: 10 Department of Pediatrics, University of Washington, Seattle, WA 98195, USA – name: 4 Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA – name: 8 Vertex Pharmaceuticals, Boston, MA 02210, USA – name: 11 Department of Pathology, University of Vermont, Colchester, VT 05405, USA – name: 1 Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, WI 53205, USA – name: 13 Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA – name: 12 Department of Biochemistry, University of Vermont, Burlington, VT 05405, USA – name: 3 Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA 98195, USA – name: 9 Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA |
| Author_xml | – sequence: 1 givenname: Paul L. surname: Auer fullname: Auer, Paul L. organization: Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, WI 53205, USA – sequence: 2 givenname: Alex P. surname: Reiner fullname: Reiner, Alex P. organization: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA – sequence: 3 givenname: Gao surname: Wang fullname: Wang, Gao organization: Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA – sequence: 4 givenname: Hyun Min surname: Kang fullname: Kang, Hyun Min organization: Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA – sequence: 5 givenname: Goncalo R. surname: Abecasis fullname: Abecasis, Goncalo R. organization: Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA – sequence: 6 givenname: David surname: Altshuler fullname: Altshuler, David organization: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA – sequence: 7 givenname: Michael J. surname: Bamshad fullname: Bamshad, Michael J. organization: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA – sequence: 8 givenname: Deborah A. surname: Nickerson fullname: Nickerson, Deborah A. organization: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA – sequence: 9 givenname: Russell P. surname: Tracy fullname: Tracy, Russell P. organization: Department of Pathology, University of Vermont, Colchester, VT 05405, USA – sequence: 10 givenname: Stephen S. surname: Rich fullname: Rich, Stephen S. organization: Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA – sequence: 11 givenname: Suzanne M. surname: Leal fullname: Leal, Suzanne M. email: sleal@bcm.edu organization: Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/27666372$$D View this record in MEDLINE/PubMed |
| BookMark | eNp9kktrGzEUhUVJaZy0f6CLIuimm3H0mlcphcTkBaYtOF0LjXTH1jAjudJMSPf94ZXjJLRZZHWF9J3DvbrnCB047wCh95TMKaHFSTdX3WY9Z-k8J9WcUPYKzWjOy6woSH6AZoQQltWsLg_RUYwdIZRWhL9Bh6wsioKXbIb-XE7WQG8dRNz6gJcqrCFbadUDXsGvCZyG7ExFMHjhh20Pd_gmKDvi0xi9tmq03uHVOBkL8TNeQrp1MVUVXJK0wQ943AD-drU8u8bnd354srVujX8E34Ee36LXreojvHuox-jnxfnN4ipbfr-8XpwuMy0qPmYqNw2vSCsMaQ1rmWqE0A1rlRaGNorUYBShnJWiLdI1ZUIJTgTUjIMgouHH6Ovedzs1AxgNbgyql9tgBxV-S6-s_P_F2Y1c-1uZkyIvKp4MPj0YBJ-GiKMcbNTQ98qBn6KkFc95XZR1mdCPz9DOT8Gl8e6pPC8SmKgP_3b01MrjghJQ7QEdfIwBWqnteP_rqUHbS0rkLguyk7ssyF0WJKlkykKSsmfSR_cXRV_2Ikh7uLUQZNR2FwJjQ9qUNN6-JP8Lya7OzA |
| CitedBy_id | crossref_primary_10_1038_s41576_022_00487_4 crossref_primary_10_1002_sim_8416 crossref_primary_10_1097_NNR_0000000000000548 crossref_primary_10_1136_jmedgenet_2019_106102 crossref_primary_10_1080_07391102_2023_2274970 crossref_primary_10_1097_SLA_0000000000004213 crossref_primary_10_3390_ijms25147939 crossref_primary_10_1093_bfgp_ely033 crossref_primary_10_1016_j_isci_2022_105336 crossref_primary_10_1186_s12864_018_4910_8 crossref_primary_10_1194_jlr_P080333 crossref_primary_10_1038_nrg_2017_89 crossref_primary_10_3389_fneur_2018_00147 crossref_primary_10_3389_fneur_2019_01362 crossref_primary_10_3389_fnagi_2021_695808 crossref_primary_10_3892_mmr_2019_9947 crossref_primary_10_1016_j_ejmg_2020_103868 crossref_primary_10_1016_j_ymgme_2024_108516 crossref_primary_10_3390_cancers13061212 crossref_primary_10_1186_s13073_022_01026_w crossref_primary_10_3390_ijms242417388 crossref_primary_10_1093_nar_gkx445 crossref_primary_10_1016_j_ajhg_2019_09_006 crossref_primary_10_1002_mgg3_294 crossref_primary_10_1038_s41431_018_0282_4 crossref_primary_10_1513_AnnalsATS_201810_716WS crossref_primary_10_1038_s41380_018_0073_x crossref_primary_10_1002_humu_23665 crossref_primary_10_1186_s13059_020_02121_0 crossref_primary_10_18632_oncotarget_22914 crossref_primary_10_1038_s43856_023_00329_2 crossref_primary_10_3390_jcdd9030065 crossref_primary_10_1038_s41598_022_09447_8 crossref_primary_10_3390_genes10110882 crossref_primary_10_1002_cphg_49 crossref_primary_10_1186_s12883_020_01873_3 crossref_primary_10_1038_s41598_017_08655_x crossref_primary_10_1093_bib_bby071 crossref_primary_10_3390_genes12030353 crossref_primary_10_1038_s41576_018_0016_z crossref_primary_10_34172_jcvtr_2021_45 crossref_primary_10_1016_j_meegid_2017_09_028 crossref_primary_10_1016_j_ajhg_2017_05_017 crossref_primary_10_3389_fphar_2021_634016 crossref_primary_10_1016_j_tcm_2017_03_005 crossref_primary_10_1038_ejhg_2016_206 crossref_primary_10_1186_s12931_017_0631_9 crossref_primary_10_1513_AnnalsATS_201706_451OC crossref_primary_10_1002_gepi_22147 crossref_primary_10_1016_j_mito_2021_03_012 crossref_primary_10_1161_CIRCRESAHA_121_318157 crossref_primary_10_1093_bioinformatics_btaa583 crossref_primary_10_1080_07853890_2017_1392595 crossref_primary_10_1038_s41525_020_0137_0 crossref_primary_10_1007_s10753_018_0787_6 crossref_primary_10_1016_j_neurobiolaging_2022_03_018 crossref_primary_10_1038_ejhg_2017_92 crossref_primary_10_3390_genes12121979 crossref_primary_10_1093_database_bax028 crossref_primary_10_3390_biomedicines13030739 crossref_primary_10_1002_gepi_22183 crossref_primary_10_1097_QAD_0000000000002894 crossref_primary_10_1002_jcb_26834 crossref_primary_10_1177_1055665619857650 crossref_primary_10_1186_s12864_023_09415_0 crossref_primary_10_1038_s41435_018_0030_3 crossref_primary_10_1097_WCO_0000000000000478 crossref_primary_10_1002_gepi_22261 |
| Cites_doi | 10.1126/science.1219240 10.1016/j.ajhg.2014.07.006 10.1056/NEJMoa1405386 10.1016/j.ajhg.2015.02.011 10.1073/pnas.1310398110 10.1001/jamaneurol.2015.0582 10.1038/nature13917 10.1038/ejhg.2014.216 10.1182/blood-2013-02-485094 10.1038/nature11247 10.1038/nature05911 10.1038/507294a 10.1093/bioinformatics/btq340 10.1086/519795 10.1016/j.ajhg.2010.04.005 10.1038/nmeth0410-248 10.1093/bioinformatics/btu296 10.1016/j.ajhg.2014.04.004 10.1038/ng.2303 10.1038/nature11690 10.1001/jama.2014.15063 10.1038/ng.2344 10.1038/ng.3643 10.1016/j.ajhg.2012.08.031 10.1056/NEJMp1500523 10.1101/gr.176552.114 10.1002/gepi.21736 10.1016/j.ajhg.2011.05.029 10.1093/bioinformatics/btq559 10.1371/journal.pgen.1003075 10.1016/j.ajhg.2013.08.006 10.1038/ejhg.2014.19 10.1093/bioinformatics/19.1.149 10.1101/gr.183483.114 10.1073/pnas.1221713110 10.1038/nature14962 10.1002/gepi.21867 10.1016/j.ajhg.2014.01.010 10.1056/NEJMoa1307095 10.1093/bioinformatics/btp324 10.1016/j.ajhg.2008.06.024 10.1093/bioinformatics/btt477 10.1093/bioinformatics/btp352 10.1093/hmg/ddu361 10.1038/ng.2892 10.1038/nrg2796 10.1038/nature15393 10.1073/pnas.0812824106 |
| ContentType | Journal Article |
| Copyright | 2016 American Society of Human Genetics Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved. Copyright Cell Press Oct 6, 2016 2016 American Society of Human Genetics. 2016 American Society of Human Genetics |
| Copyright_xml | – notice: 2016 American Society of Human Genetics – notice: Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved. – notice: Copyright Cell Press Oct 6, 2016 – notice: 2016 American Society of Human Genetics. 2016 American Society of Human Genetics |
| CorporateAuthor | NHLBI GO Exome Sequencing Project |
| CorporateAuthor_xml | – name: NHLBI GO Exome Sequencing Project |
| DBID | 6I. AAFTH AAYXX CITATION CGR CUY CVF ECM EIF NPM 7QP 7TK 7TM 7U7 8FD C1K FR3 K9. NAPCQ P64 RC3 7X8 5PM |
| DOI | 10.1016/j.ajhg.2016.08.012 |
| DatabaseName | ScienceDirect Open Access Titles Elsevier:ScienceDirect:Open Access CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed Calcium & Calcified Tissue Abstracts Neurosciences Abstracts Nucleic Acids Abstracts Toxicology Abstracts Technology Research Database Environmental Sciences and Pollution Management Engineering Research Database ProQuest Health & Medical Complete (Alumni) Nursing & Allied Health Premium Biotechnology and BioEngineering Abstracts Genetics Abstracts MEDLINE - Academic PubMed Central (Full Participant titles) |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) Nursing & Allied Health Premium Genetics Abstracts Technology Research Database Toxicology Abstracts Nucleic Acids Abstracts ProQuest Health & Medical Complete (Alumni) Engineering Research Database Calcium & Calcified Tissue Abstracts Neurosciences Abstracts Biotechnology and BioEngineering Abstracts Environmental Sciences and Pollution Management MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic Nursing & Allied Health Premium MEDLINE |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Biology |
| EISSN | 1537-6605 |
| EndPage | 801 |
| ExternalDocumentID | PMC5065683 4237331201 27666372 10_1016_j_ajhg_2016_08_012 S0002929716303378 |
| Genre | Journal Article |
| GrantInformation_xml | – fundername: NHLBI NIH HHS grantid: RC2 HL103010 – fundername: NHGRI NIH HHS grantid: U24 HG007307 – fundername: NHLBI NIH HHS grantid: RC2 HL102924 – fundername: NHLBI NIH HHS grantid: RC2 HL102923 – fundername: NHLBI NIH HHS grantid: RC2 HL102926 – fundername: NHLBI NIH HHS grantid: RC2 HL102925 – fundername: NHGRI NIH HHS grantid: R01 HG008972 – fundername: NLM NIH HHS grantid: T15 LM007442 |
| GroupedDBID | --- --K --Z -~X 0R~ 123 1~5 23M 2WC 4.4 457 4G. 53G 5GY 62- 6I. 6J9 7-5 85S AACTN AAEDT AAEDW AAFTH AAIAV AAKRW AALRI AAUCE AAVLU AAWTL AAXJY AAXUO ABJNI ABMAC ABMWF ABOCM ABVKL ACGFO ACGFS ACGOD ACNCT ACPRK ADBBV ADEZE ADJPV AENEX AEXQZ AFRAH AFTJW AGKMS AHMBA AITUG ALKID ALMA_UNASSIGNED_HOLDINGS AMRAJ AOIJS ASPBG AVWKF AZFZN BAWUL CS3 D0L DIK E3Z EBS ECV EJD F5P FCP FDB FEDTE GX1 HVGLF HYE IH2 IHE IXB JIG KQ8 L7B M41 NCXOZ O-L O9- OK1 P2P PQQKQ RCE RIG RNS ROL RPM RPZ SES SJN SSZ TN5 TR2 TWZ UHB UKR UNMZH UPT VQA WH7 WQ6 ZA5 ZCA .55 .GJ 34R 3O- 41~ AAFWJ AAIKJ AAMRU AAQXK AAYWO AAYXX ABDGV ABWVN ACKIV ACRPL ACVFH ADCNI ADMUD ADNMO ADVLN ADXHL AEUPX AFPUW AGCDD AGCQF AGHFR AGQPQ AI. AIGII AKAPO AKBMS AKRWK AKYEP APXCP C1A CITATION FA8 FGOYB HZ~ MVM NEJ OHT OZT R2- VH1 WOQ X7M XOL ZCG ZGI ZXP CGR CUY CVF ECM EFKBS EIF NPM 7QP 7TK 7TM 7U7 8FD C1K FR3 K9. NAPCQ P64 RC3 7X8 5PM |
| ID | FETCH-LOGICAL-c483t-a5db380f4d0fd2f2ab44cb2fac4d1ba09eda013274f6b2f124a4304e923e404b3 |
| IEDL.DBID | IXB |
| ISSN | 0002-9297 1537-6605 |
| IngestDate | Thu Aug 21 18:24:44 EDT 2025 Sun Sep 28 00:58:45 EDT 2025 Fri Jul 25 19:56:40 EDT 2025 Mon Jul 21 05:59:24 EDT 2025 Tue Jul 01 03:39:15 EDT 2025 Thu Apr 24 23:07:05 EDT 2025 Fri Feb 23 02:29:25 EST 2024 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 4 |
| Language | English |
| License | This article is made available under the Elsevier license. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c483t-a5db380f4d0fd2f2ab44cb2fac4d1ba09eda013274f6b2f124a4304e923e404b3 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
| OpenAccessLink | https://www.sciencedirect.com/science/article/pii/S0002929716303378 |
| PMID | 27666372 |
| PQID | 1835556396 |
| PQPubID | 24320 |
| PageCount | 11 |
| ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_5065683 proquest_miscellaneous_1835396797 proquest_journals_1835556396 pubmed_primary_27666372 crossref_citationtrail_10_1016_j_ajhg_2016_08_012 crossref_primary_10_1016_j_ajhg_2016_08_012 elsevier_sciencedirect_doi_10_1016_j_ajhg_2016_08_012 |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | 2016-10-06 |
| PublicationDateYYYYMMDD | 2016-10-06 |
| PublicationDate_xml | – month: 10 year: 2016 text: 2016-10-06 day: 06 |
| PublicationDecade | 2010 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States – name: Chicago |
| PublicationTitle | American journal of human genetics |
| PublicationTitleAlternate | Am J Hum Genet |
| PublicationYear | 2016 |
| Publisher | Elsevier Inc Cell Press Elsevier |
| Publisher_xml | – name: Elsevier Inc – name: Cell Press – name: Elsevier |
| References | Auer, Nalls, Meschia, Worrall, Longstreth, Seshadri, Kooperberg, Burger, Carlson, Carty (bib32) 2015; 72 Auer, Wang, Leal (bib14) 2013; 37 Kryukov, Shpunt, Stamatoyannopoulos, Sunyaev (bib26) 2009; 106 Lange, Hu, Zhang, Xue, Schmidt, Tang, Bizon, Lange, Smith, Turner (bib31) 2014; 94 Kircher, Witten, Jain, O’Roak, Cooper, Shendure (bib17) 2014; 46 Auer, Johnsen, Johnson, Logsdon, Lange, Nalls, Zhang, Franceschini, Fox, Lange (bib20) 2012; 91 Wang, Peng, Leal (bib18) 2014; 94 Li, Leal (bib12) 2008; 83 Deelen, Menelaou, van Leeuwen, Kanterakis, van Dijk, Medina-Gomez, Francioli, Hottenga, Karssen, Estrada (bib46) 2014; 22 Liu, Leal (bib42) 2012; 8 Consortium (bib44) 2012; 489 Collins, Varmus (bib1) 2015; 372 Wu, Lee, Cai, Li, Boehnke, Lin (bib13) 2011; 89 Kiezun, Garimella, Do, Stitziel, Neale, McLaren, Gupta, Sklar, Sullivan, Moran (bib45) 2012; 44 Willer, Li, Abecasis (bib11) 2010; 26 Peng (bib25) 2015; 39 Tennessen, Bigham, O’Connor, Fu, Kenny, Gravel, McGee, Do, Liu, Jun (bib30) 2012; 337 Adzhubei, Schmidt, Peshkin, Ramensky, Gerasimova, Bork, Kondrashov, Sunyaev (bib16) 2010; 7 Do, Stitziel, Won, Jørgensen, Duga, Angelica Merlini, Kiezun, Farrall, Goel, Zuk (bib33) 2015; 518 Li, Durbin (bib2) 2009; 25 McCarthy, Das, Kretzschmar, Delaneau, Wood, Teumer, Kang, Fuchsberger, Danecek, Sharp (bib48) 2016 Emond, Louie, Emerson, Zhao, Mathias, Knowles, Wright, Rieder, Tabor, Nickerson (bib34) 2012; 44 Gazave, Ma, Chang, Coventry, Gao, Muzny, Boerwinkle, Gibbs, Sing, Clark, Keinan (bib24) 2014; 111 Jun, Wing, Abecasis, Kang (bib4) 2015; 25 Crosby, Peloso, Auer, Crosslin, Stitziel, Lange, Lu, Tang, Zhang, Hindy (bib9) 2014; 371 Amendola, Dorschner, Robertson, Salama, Hart, Shirts, Murray, Tokita, Gallego, Kim (bib38) 2015; 25 Purcell, Cherny, Sham (bib37) 2003; 19 Wang, Li, Santos-Cortez, Peng, Leal (bib27) 2014; 30 Lin, Zeng, Tang (bib41) 2013; 110 Duan, Liu, Auer, Zhang, Lange, Jun, Bizon, Jiao, Buyske, Franceschini (bib22) 2013; 29 Scheidecker, Etard, Haren, Stoetzel, Hull, Arno, Plagnol, Drunat, Passemard, Toutain (bib15) 2015; 96 Marchini, Howie (bib19) 2010; 11 Li, Handsaker, Wysoker, Fennell, Ruan, Homer, Marth, Abecasis, Durbin (bib3) 2009; 25 Walter, Min, Huang, Crooks, Memari, McCarthy, Perry, Xu, Futema, Lawson (bib28) 2015; 526 Du, Auer, Jiao, Haessler, Altshuler, Boerwinkle, Carlson, Carty, Chen, Curtis (bib21) 2014; 23 Purcell, Neale, Todd-Brown, Thomas, Ferreira, Bender, Maller, Sklar, de Bakker, Daly, Sham (bib5) 2007; 81 Manichaikul, Mychaleckyj, Rich, Daly, Sale, Chen (bib6) 2010; 26 Stitziel, Won, Morrison, Peloso, Do, Lange, Fontanillas, Gupta, Duga, Goel (bib35) 2014; 371 Auton, Brooks, Durbin, Garrison, Kang, Korbel, Marchini, McCarthy, McVean, Abecasis (bib29) 2015; 526 Johnsen, Auer, Morrison, Jiao, Wei, Haessler, Fox, McGee, Smith, Carlson (bib23) 2013; 122 Naik, Derebail, Grams, Franceschini, Auer, Peloso, Young, Lettre, Peralta, Katz (bib36) 2014; 312 Fu, O’Connor, Jun, Kang, Abecasis, Leal, Gabriel, Rieder, Altshuler, Shendure (bib8) 2013; 493 Tabor, Auer, Jamal, Chong, Yu, Gordon, Graubert, O’Donnell, Rich, Nickerson, Bamshad (bib40) 2014; 95 (bib7) 2007; 447 Price, Kryukov, de Bakker, Purcell, Staples, Wei, Sunyaev (bib10) 2010; 86 Dorschner, Amendola, Turner, Robertson, Shirts, Gallego, Bennett, Jones, Tokita, Bennett (bib39) 2013; 93 Hayden (bib43) 2014; 507 Pistis, Porcu, Vrieze, Sidore, Steri, Danjou, Busonero, Mulas, Zoledziewska, Maschio (bib47) 2015; 23 Lange (10.1016/j.ajhg.2016.08.012_bib31) 2014; 94 Emond (10.1016/j.ajhg.2016.08.012_bib34) 2012; 44 Du (10.1016/j.ajhg.2016.08.012_bib21) 2014; 23 Fu (10.1016/j.ajhg.2016.08.012_bib8) 2013; 493 Do (10.1016/j.ajhg.2016.08.012_bib33) 2015; 518 Crosby (10.1016/j.ajhg.2016.08.012_bib9) 2014; 371 Wang (10.1016/j.ajhg.2016.08.012_bib27) 2014; 30 (10.1016/j.ajhg.2016.08.012_bib7) 2007; 447 Scheidecker (10.1016/j.ajhg.2016.08.012_bib15) 2015; 96 Stitziel (10.1016/j.ajhg.2016.08.012_bib35) 2014; 371 Consortium (10.1016/j.ajhg.2016.08.012_bib44) 2012; 489 Li (10.1016/j.ajhg.2016.08.012_bib3) 2009; 25 Pistis (10.1016/j.ajhg.2016.08.012_bib47) 2015; 23 Marchini (10.1016/j.ajhg.2016.08.012_bib19) 2010; 11 Auer (10.1016/j.ajhg.2016.08.012_bib14) 2013; 37 Collins (10.1016/j.ajhg.2016.08.012_bib1) 2015; 372 Manichaikul (10.1016/j.ajhg.2016.08.012_bib6) 2010; 26 Liu (10.1016/j.ajhg.2016.08.012_bib42) 2012; 8 Duan (10.1016/j.ajhg.2016.08.012_bib22) 2013; 29 Adzhubei (10.1016/j.ajhg.2016.08.012_bib16) 2010; 7 Li (10.1016/j.ajhg.2016.08.012_bib12) 2008; 83 McCarthy (10.1016/j.ajhg.2016.08.012_bib48) 2016 Amendola (10.1016/j.ajhg.2016.08.012_bib38) 2015; 25 Purcell (10.1016/j.ajhg.2016.08.012_bib37) 2003; 19 Kryukov (10.1016/j.ajhg.2016.08.012_bib26) 2009; 106 Price (10.1016/j.ajhg.2016.08.012_bib10) 2010; 86 Tabor (10.1016/j.ajhg.2016.08.012_bib40) 2014; 95 Kircher (10.1016/j.ajhg.2016.08.012_bib17) 2014; 46 Willer (10.1016/j.ajhg.2016.08.012_bib11) 2010; 26 Auton (10.1016/j.ajhg.2016.08.012_bib29) 2015; 526 Li (10.1016/j.ajhg.2016.08.012_bib2) 2009; 25 Lin (10.1016/j.ajhg.2016.08.012_bib41) 2013; 110 Peng (10.1016/j.ajhg.2016.08.012_bib25) 2015; 39 Auer (10.1016/j.ajhg.2016.08.012_bib20) 2012; 91 Auer (10.1016/j.ajhg.2016.08.012_bib32) 2015; 72 Kiezun (10.1016/j.ajhg.2016.08.012_bib45) 2012; 44 Jun (10.1016/j.ajhg.2016.08.012_bib4) 2015; 25 Naik (10.1016/j.ajhg.2016.08.012_bib36) 2014; 312 Gazave (10.1016/j.ajhg.2016.08.012_bib24) 2014; 111 Wang (10.1016/j.ajhg.2016.08.012_bib18) 2014; 94 Tennessen (10.1016/j.ajhg.2016.08.012_bib30) 2012; 337 Hayden (10.1016/j.ajhg.2016.08.012_bib43) 2014; 507 Purcell (10.1016/j.ajhg.2016.08.012_bib5) 2007; 81 Wu (10.1016/j.ajhg.2016.08.012_bib13) 2011; 89 Dorschner (10.1016/j.ajhg.2016.08.012_bib39) 2013; 93 Deelen (10.1016/j.ajhg.2016.08.012_bib46) 2014; 22 Johnsen (10.1016/j.ajhg.2016.08.012_bib23) 2013; 122 Walter (10.1016/j.ajhg.2016.08.012_bib28) 2015; 526 |
| References_xml | – year: 2016 ident: bib48 article-title: A reference panel of 64,976 haplotypes for genotype imputation publication-title: Nat. Genet. – volume: 371 start-page: 2072 year: 2014 end-page: 2082 ident: bib35 article-title: Inactivating mutations in NPC1L1 and protection from coronary heart disease publication-title: N. Engl. J. Med. – volume: 25 start-page: 1754 year: 2009 end-page: 1760 ident: bib2 article-title: Fast and accurate short read alignment with Burrows-Wheeler transform publication-title: Bioinformatics – volume: 106 start-page: 3871 year: 2009 end-page: 3876 ident: bib26 article-title: Power of deep, all-exon resequencing for discovery of human trait genes publication-title: Proc. Natl. Acad. Sci. USA – volume: 25 start-page: 305 year: 2015 end-page: 315 ident: bib38 article-title: Actionable exomic incidental findings in 6503 participants: challenges of variant classification publication-title: Genome Res. – volume: 83 start-page: 311 year: 2008 end-page: 321 ident: bib12 article-title: Methods for detecting associations with rare variants for common diseases: application to analysis of sequence data publication-title: Am. J. Hum. Genet. – volume: 89 start-page: 82 year: 2011 end-page: 93 ident: bib13 article-title: Rare-variant association testing for sequencing data with the sequence kernel association test publication-title: Am. J. Hum. Genet. – volume: 312 start-page: 2115 year: 2014 end-page: 2125 ident: bib36 article-title: Association of sickle cell trait with chronic kidney disease and albuminuria in African Americans publication-title: JAMA – volume: 23 start-page: 975 year: 2015 end-page: 983 ident: bib47 article-title: Rare variant genotype imputation with thousands of study-specific whole-genome sequences: implications for cost-effective study designs publication-title: Eur. J. Hum. Genet. – volume: 22 start-page: 1321 year: 2014 end-page: 1326 ident: bib46 article-title: Improved imputation quality of low-frequency and rare variants in European samples using the ‘Genome of The Netherlands’ publication-title: Eur. J. Hum. Genet. – volume: 94 start-page: 233 year: 2014 end-page: 245 ident: bib31 article-title: Whole-exome sequencing identifies rare and low-frequency coding variants associated with LDL cholesterol publication-title: Am. J. Hum. Genet. – volume: 94 start-page: 770 year: 2014 end-page: 783 ident: bib18 article-title: Variant association tools for quality control and analysis of large-scale sequence and genotyping array data publication-title: Am. J. Hum. Genet. – volume: 25 start-page: 2078 year: 2009 end-page: 2079 ident: bib3 article-title: The Sequence Alignment/Map format and SAMtools publication-title: Bioinformatics – volume: 26 start-page: 2867 year: 2010 end-page: 2873 ident: bib6 article-title: Robust relationship inference in genome-wide association studies publication-title: Bioinformatics – volume: 44 start-page: 623 year: 2012 end-page: 630 ident: bib45 article-title: Exome sequencing and the genetic basis of complex traits publication-title: Nat. Genet. – volume: 19 start-page: 149 year: 2003 end-page: 150 ident: bib37 article-title: Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits publication-title: Bioinformatics – volume: 25 start-page: 918 year: 2015 end-page: 925 ident: bib4 article-title: An efficient and scalable analysis framework for variant extraction and refinement from population-scale DNA sequence data publication-title: Genome Res. – volume: 26 start-page: 2190 year: 2010 end-page: 2191 ident: bib11 article-title: METAL: fast and efficient meta-analysis of genomewide association scans publication-title: Bioinformatics – volume: 507 start-page: 294 year: 2014 end-page: 295 ident: bib43 article-title: Technology: The $1,000 genome publication-title: Nature – volume: 447 start-page: 661 year: 2007 end-page: 678 ident: bib7 article-title: Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls publication-title: Nature – volume: 95 start-page: 183 year: 2014 end-page: 193 ident: bib40 article-title: Pathogenic variants for Mendelian and complex traits in exomes of 6,517 European and African Americans: implications for the return of incidental results publication-title: Am. J. Hum. Genet. – volume: 29 start-page: 2744 year: 2013 end-page: 2749 ident: bib22 article-title: Imputation of coding variants in African Americans: better performance using data from the exome sequencing project publication-title: Bioinformatics – volume: 526 start-page: 82 year: 2015 end-page: 90 ident: bib28 article-title: The UK10K project identifies rare variants in health and disease publication-title: Nature – volume: 7 start-page: 248 year: 2010 end-page: 249 ident: bib16 article-title: A method and server for predicting damaging missense mutations publication-title: Nat. Methods – volume: 518 start-page: 102 year: 2015 end-page: 106 ident: bib33 article-title: Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction publication-title: Nature – volume: 489 start-page: 57 year: 2012 end-page: 74 ident: bib44 article-title: An integrated encyclopedia of DNA elements in the human genome publication-title: Nature – volume: 96 start-page: 666 year: 2015 end-page: 674 ident: bib15 article-title: Mutations in TUBGCP4 alter microtubule organization via the γ-tubulin ring complex in autosomal-recessive microcephaly with chorioretinopathy publication-title: Am. J. Hum. Genet. – volume: 372 start-page: 793 year: 2015 end-page: 795 ident: bib1 article-title: A new initiative on precision medicine publication-title: N. Engl. J. Med. – volume: 11 start-page: 499 year: 2010 end-page: 511 ident: bib19 article-title: Genotype imputation for genome-wide association studies publication-title: Nat. Rev. Genet. – volume: 72 start-page: 781 year: 2015 end-page: 788 ident: bib32 article-title: Rare and coding region genetic variants associated with risk of ischemic stroke: The NHLBI Exome Sequence Project publication-title: JAMA Neurol. – volume: 122 start-page: 590 year: 2013 end-page: 597 ident: bib23 article-title: Common and rare von Willebrand factor (VWF) coding variants, VWF levels, and factor VIII levels in African Americans: the NHLBI Exome Sequencing Project publication-title: Blood – volume: 111 start-page: 757 year: 2014 end-page: 762 ident: bib24 article-title: Neutral genomic regions refine models of recent rapid human population growth publication-title: Proc. Natl. Acad. Sci. USA – volume: 91 start-page: 794 year: 2012 end-page: 808 ident: bib20 article-title: Imputation of exome sequence variants into population- based samples and blood-cell-trait-associated loci in African Americans: NHLBI GO Exome Sequencing Project publication-title: Am. J. Hum. Genet. – volume: 110 start-page: 12247 year: 2013 end-page: 12252 ident: bib41 article-title: Quantitative trait analysis in sequencing studies under trait-dependent sampling publication-title: Proc. Natl. Acad. Sci. USA – volume: 39 start-page: 45 year: 2015 end-page: 52 ident: bib25 article-title: Reproducible simulations of realistic samples for next-generation sequencing studies using Variant Simulation Tools publication-title: Genet. Epidemiol. – volume: 44 start-page: 886 year: 2012 end-page: 889 ident: bib34 article-title: Exome sequencing of extreme phenotypes identifies DCTN4 as a modifier of chronic publication-title: Nat. Genet. – volume: 493 start-page: 216 year: 2013 end-page: 220 ident: bib8 article-title: Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants publication-title: Nature – volume: 37 start-page: 529 year: 2013 end-page: 538 ident: bib14 article-title: Testing for rare variant associations in the presence of missing data publication-title: Genet. Epidemiol. – volume: 30 start-page: 2377 year: 2014 end-page: 2378 ident: bib27 article-title: Power analysis and sample size estimation for sequence-based association studies publication-title: Bioinformatics – volume: 93 start-page: 631 year: 2013 end-page: 640 ident: bib39 article-title: Actionable, pathogenic incidental findings in 1,000 participants’ exomes publication-title: Am. J. Hum. Genet. – volume: 337 start-page: 64 year: 2012 end-page: 69 ident: bib30 article-title: Evolution and functional impact of rare coding variation from deep sequencing of human exomes publication-title: Science – volume: 8 start-page: e1003075 year: 2012 ident: bib42 article-title: A unified method for detecting secondary trait associations with rare variants: application to sequence data publication-title: PLoS Genet. – volume: 526 start-page: 68 year: 2015 end-page: 74 ident: bib29 article-title: A global reference for human genetic variation publication-title: Nature – volume: 81 start-page: 559 year: 2007 end-page: 575 ident: bib5 article-title: PLINK: a tool set for whole-genome association and population-based linkage analyses publication-title: Am. J. Hum. Genet. – volume: 86 start-page: 832 year: 2010 end-page: 838 ident: bib10 article-title: Pooled association tests for rare variants in exon-resequencing studies publication-title: Am. J. Hum. Genet. – volume: 46 start-page: 310 year: 2014 end-page: 315 ident: bib17 article-title: A general framework for estimating the relative pathogenicity of human genetic variants publication-title: Nat. Genet. – volume: 371 start-page: 22 year: 2014 end-page: 31 ident: bib9 article-title: Loss-of-function mutations in APOC3, triglycerides, and coronary disease publication-title: N. Engl. J. Med. – volume: 23 start-page: 6607 year: 2014 end-page: 6615 ident: bib21 article-title: Whole-exome imputation of sequence variants identified two novel alleles associated with adult body height in African Americans publication-title: Hum. Mol. Genet. – volume: 337 start-page: 64 year: 2012 ident: 10.1016/j.ajhg.2016.08.012_bib30 article-title: Evolution and functional impact of rare coding variation from deep sequencing of human exomes publication-title: Science doi: 10.1126/science.1219240 – volume: 95 start-page: 183 year: 2014 ident: 10.1016/j.ajhg.2016.08.012_bib40 article-title: Pathogenic variants for Mendelian and complex traits in exomes of 6,517 European and African Americans: implications for the return of incidental results publication-title: Am. J. Hum. Genet. doi: 10.1016/j.ajhg.2014.07.006 – volume: 371 start-page: 2072 year: 2014 ident: 10.1016/j.ajhg.2016.08.012_bib35 article-title: Inactivating mutations in NPC1L1 and protection from coronary heart disease publication-title: N. Engl. J. Med. doi: 10.1056/NEJMoa1405386 – volume: 96 start-page: 666 year: 2015 ident: 10.1016/j.ajhg.2016.08.012_bib15 article-title: Mutations in TUBGCP4 alter microtubule organization via the γ-tubulin ring complex in autosomal-recessive microcephaly with chorioretinopathy publication-title: Am. J. Hum. Genet. doi: 10.1016/j.ajhg.2015.02.011 – volume: 111 start-page: 757 year: 2014 ident: 10.1016/j.ajhg.2016.08.012_bib24 article-title: Neutral genomic regions refine models of recent rapid human population growth publication-title: Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.1310398110 – volume: 72 start-page: 781 year: 2015 ident: 10.1016/j.ajhg.2016.08.012_bib32 article-title: Rare and coding region genetic variants associated with risk of ischemic stroke: The NHLBI Exome Sequence Project publication-title: JAMA Neurol. doi: 10.1001/jamaneurol.2015.0582 – volume: 518 start-page: 102 year: 2015 ident: 10.1016/j.ajhg.2016.08.012_bib33 article-title: Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction publication-title: Nature doi: 10.1038/nature13917 – volume: 23 start-page: 975 year: 2015 ident: 10.1016/j.ajhg.2016.08.012_bib47 article-title: Rare variant genotype imputation with thousands of study-specific whole-genome sequences: implications for cost-effective study designs publication-title: Eur. J. Hum. Genet. doi: 10.1038/ejhg.2014.216 – volume: 122 start-page: 590 year: 2013 ident: 10.1016/j.ajhg.2016.08.012_bib23 article-title: Common and rare von Willebrand factor (VWF) coding variants, VWF levels, and factor VIII levels in African Americans: the NHLBI Exome Sequencing Project publication-title: Blood doi: 10.1182/blood-2013-02-485094 – volume: 489 start-page: 57 year: 2012 ident: 10.1016/j.ajhg.2016.08.012_bib44 article-title: An integrated encyclopedia of DNA elements in the human genome publication-title: Nature doi: 10.1038/nature11247 – volume: 447 start-page: 661 year: 2007 ident: 10.1016/j.ajhg.2016.08.012_bib7 article-title: Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls publication-title: Nature doi: 10.1038/nature05911 – volume: 507 start-page: 294 year: 2014 ident: 10.1016/j.ajhg.2016.08.012_bib43 article-title: Technology: The $1,000 genome publication-title: Nature doi: 10.1038/507294a – volume: 26 start-page: 2190 year: 2010 ident: 10.1016/j.ajhg.2016.08.012_bib11 article-title: METAL: fast and efficient meta-analysis of genomewide association scans publication-title: Bioinformatics doi: 10.1093/bioinformatics/btq340 – volume: 81 start-page: 559 year: 2007 ident: 10.1016/j.ajhg.2016.08.012_bib5 article-title: PLINK: a tool set for whole-genome association and population-based linkage analyses publication-title: Am. J. Hum. Genet. doi: 10.1086/519795 – volume: 86 start-page: 832 year: 2010 ident: 10.1016/j.ajhg.2016.08.012_bib10 article-title: Pooled association tests for rare variants in exon-resequencing studies publication-title: Am. J. Hum. Genet. doi: 10.1016/j.ajhg.2010.04.005 – volume: 7 start-page: 248 year: 2010 ident: 10.1016/j.ajhg.2016.08.012_bib16 article-title: A method and server for predicting damaging missense mutations publication-title: Nat. Methods doi: 10.1038/nmeth0410-248 – volume: 30 start-page: 2377 year: 2014 ident: 10.1016/j.ajhg.2016.08.012_bib27 article-title: Power analysis and sample size estimation for sequence-based association studies publication-title: Bioinformatics doi: 10.1093/bioinformatics/btu296 – volume: 94 start-page: 770 year: 2014 ident: 10.1016/j.ajhg.2016.08.012_bib18 article-title: Variant association tools for quality control and analysis of large-scale sequence and genotyping array data publication-title: Am. J. Hum. Genet. doi: 10.1016/j.ajhg.2014.04.004 – volume: 44 start-page: 623 year: 2012 ident: 10.1016/j.ajhg.2016.08.012_bib45 article-title: Exome sequencing and the genetic basis of complex traits publication-title: Nat. Genet. doi: 10.1038/ng.2303 – volume: 493 start-page: 216 year: 2013 ident: 10.1016/j.ajhg.2016.08.012_bib8 article-title: Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants publication-title: Nature doi: 10.1038/nature11690 – volume: 312 start-page: 2115 year: 2014 ident: 10.1016/j.ajhg.2016.08.012_bib36 article-title: Association of sickle cell trait with chronic kidney disease and albuminuria in African Americans publication-title: JAMA doi: 10.1001/jama.2014.15063 – volume: 44 start-page: 886 year: 2012 ident: 10.1016/j.ajhg.2016.08.012_bib34 article-title: Exome sequencing of extreme phenotypes identifies DCTN4 as a modifier of chronic Pseudomonas aeruginosa infection in cystic fibrosis publication-title: Nat. Genet. doi: 10.1038/ng.2344 – year: 2016 ident: 10.1016/j.ajhg.2016.08.012_bib48 article-title: A reference panel of 64,976 haplotypes for genotype imputation publication-title: Nat. Genet. doi: 10.1038/ng.3643 – volume: 91 start-page: 794 year: 2012 ident: 10.1016/j.ajhg.2016.08.012_bib20 article-title: Imputation of exome sequence variants into population- based samples and blood-cell-trait-associated loci in African Americans: NHLBI GO Exome Sequencing Project publication-title: Am. J. Hum. Genet. doi: 10.1016/j.ajhg.2012.08.031 – volume: 372 start-page: 793 year: 2015 ident: 10.1016/j.ajhg.2016.08.012_bib1 article-title: A new initiative on precision medicine publication-title: N. Engl. J. Med. doi: 10.1056/NEJMp1500523 – volume: 25 start-page: 918 year: 2015 ident: 10.1016/j.ajhg.2016.08.012_bib4 article-title: An efficient and scalable analysis framework for variant extraction and refinement from population-scale DNA sequence data publication-title: Genome Res. doi: 10.1101/gr.176552.114 – volume: 37 start-page: 529 year: 2013 ident: 10.1016/j.ajhg.2016.08.012_bib14 article-title: Testing for rare variant associations in the presence of missing data publication-title: Genet. Epidemiol. doi: 10.1002/gepi.21736 – volume: 89 start-page: 82 year: 2011 ident: 10.1016/j.ajhg.2016.08.012_bib13 article-title: Rare-variant association testing for sequencing data with the sequence kernel association test publication-title: Am. J. Hum. Genet. doi: 10.1016/j.ajhg.2011.05.029 – volume: 26 start-page: 2867 year: 2010 ident: 10.1016/j.ajhg.2016.08.012_bib6 article-title: Robust relationship inference in genome-wide association studies publication-title: Bioinformatics doi: 10.1093/bioinformatics/btq559 – volume: 8 start-page: e1003075 year: 2012 ident: 10.1016/j.ajhg.2016.08.012_bib42 article-title: A unified method for detecting secondary trait associations with rare variants: application to sequence data publication-title: PLoS Genet. doi: 10.1371/journal.pgen.1003075 – volume: 93 start-page: 631 year: 2013 ident: 10.1016/j.ajhg.2016.08.012_bib39 article-title: Actionable, pathogenic incidental findings in 1,000 participants’ exomes publication-title: Am. J. Hum. Genet. doi: 10.1016/j.ajhg.2013.08.006 – volume: 22 start-page: 1321 year: 2014 ident: 10.1016/j.ajhg.2016.08.012_bib46 article-title: Improved imputation quality of low-frequency and rare variants in European samples using the ‘Genome of The Netherlands’ publication-title: Eur. J. Hum. Genet. doi: 10.1038/ejhg.2014.19 – volume: 19 start-page: 149 year: 2003 ident: 10.1016/j.ajhg.2016.08.012_bib37 article-title: Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits publication-title: Bioinformatics doi: 10.1093/bioinformatics/19.1.149 – volume: 25 start-page: 305 year: 2015 ident: 10.1016/j.ajhg.2016.08.012_bib38 article-title: Actionable exomic incidental findings in 6503 participants: challenges of variant classification publication-title: Genome Res. doi: 10.1101/gr.183483.114 – volume: 110 start-page: 12247 year: 2013 ident: 10.1016/j.ajhg.2016.08.012_bib41 article-title: Quantitative trait analysis in sequencing studies under trait-dependent sampling publication-title: Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.1221713110 – volume: 526 start-page: 82 year: 2015 ident: 10.1016/j.ajhg.2016.08.012_bib28 article-title: The UK10K project identifies rare variants in health and disease publication-title: Nature doi: 10.1038/nature14962 – volume: 39 start-page: 45 year: 2015 ident: 10.1016/j.ajhg.2016.08.012_bib25 article-title: Reproducible simulations of realistic samples for next-generation sequencing studies using Variant Simulation Tools publication-title: Genet. Epidemiol. doi: 10.1002/gepi.21867 – volume: 94 start-page: 233 year: 2014 ident: 10.1016/j.ajhg.2016.08.012_bib31 article-title: Whole-exome sequencing identifies rare and low-frequency coding variants associated with LDL cholesterol publication-title: Am. J. Hum. Genet. doi: 10.1016/j.ajhg.2014.01.010 – volume: 371 start-page: 22 year: 2014 ident: 10.1016/j.ajhg.2016.08.012_bib9 article-title: Loss-of-function mutations in APOC3, triglycerides, and coronary disease publication-title: N. Engl. J. Med. doi: 10.1056/NEJMoa1307095 – volume: 25 start-page: 1754 year: 2009 ident: 10.1016/j.ajhg.2016.08.012_bib2 article-title: Fast and accurate short read alignment with Burrows-Wheeler transform publication-title: Bioinformatics doi: 10.1093/bioinformatics/btp324 – volume: 83 start-page: 311 year: 2008 ident: 10.1016/j.ajhg.2016.08.012_bib12 article-title: Methods for detecting associations with rare variants for common diseases: application to analysis of sequence data publication-title: Am. J. Hum. Genet. doi: 10.1016/j.ajhg.2008.06.024 – volume: 29 start-page: 2744 year: 2013 ident: 10.1016/j.ajhg.2016.08.012_bib22 article-title: Imputation of coding variants in African Americans: better performance using data from the exome sequencing project publication-title: Bioinformatics doi: 10.1093/bioinformatics/btt477 – volume: 25 start-page: 2078 year: 2009 ident: 10.1016/j.ajhg.2016.08.012_bib3 article-title: The Sequence Alignment/Map format and SAMtools publication-title: Bioinformatics doi: 10.1093/bioinformatics/btp352 – volume: 23 start-page: 6607 year: 2014 ident: 10.1016/j.ajhg.2016.08.012_bib21 article-title: Whole-exome imputation of sequence variants identified two novel alleles associated with adult body height in African Americans publication-title: Hum. Mol. Genet. doi: 10.1093/hmg/ddu361 – volume: 46 start-page: 310 year: 2014 ident: 10.1016/j.ajhg.2016.08.012_bib17 article-title: A general framework for estimating the relative pathogenicity of human genetic variants publication-title: Nat. Genet. doi: 10.1038/ng.2892 – volume: 11 start-page: 499 year: 2010 ident: 10.1016/j.ajhg.2016.08.012_bib19 article-title: Genotype imputation for genome-wide association studies publication-title: Nat. Rev. Genet. doi: 10.1038/nrg2796 – volume: 526 start-page: 68 year: 2015 ident: 10.1016/j.ajhg.2016.08.012_bib29 article-title: A global reference for human genetic variation publication-title: Nature doi: 10.1038/nature15393 – volume: 106 start-page: 3871 year: 2009 ident: 10.1016/j.ajhg.2016.08.012_bib26 article-title: Power of deep, all-exon resequencing for discovery of human trait genes publication-title: Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.0812824106 |
| SSID | ssj0011803 |
| Score | 2.4916055 |
| Snippet | Massively parallel whole-genome sequencing (WGS) data have ushered in a new era in human genetics. These data are now being used to understand the role of rare... |
| SourceID | pubmedcentral proquest pubmed crossref elsevier |
| SourceType | Open Access Repository Aggregation Database Index Database Enrichment Source Publisher |
| StartPage | 791 |
| SubjectTerms | Exome - genetics Female Genetic Association Studies - methods Genetic Association Studies - standards Genetic Variation Genetics Genome, Human - genetics Genomics Guidelines as Topic Humans Male National Heart, Lung, and Blood Institute (U.S.) Quality Control Reproducibility of Results Sample size Sequence Analysis, DNA Technological change United States |
| Title | Guidelines for Large-Scale Sequence-Based Complex Trait Association Studies: Lessons Learned from the NHLBI Exome Sequencing Project |
| URI | https://dx.doi.org/10.1016/j.ajhg.2016.08.012 https://www.ncbi.nlm.nih.gov/pubmed/27666372 https://www.proquest.com/docview/1835556396 https://www.proquest.com/docview/1835396797 https://pubmed.ncbi.nlm.nih.gov/PMC5065683 |
| Volume | 99 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1NS8QwEA0iCF7Eb9cvIniTYtukSevNFXXVVQQV9haSNnVXtCu6C3r3hzvTpsVV9OCx6aR0O8m8l82bCSG7VttIC2NgWRIwj_ME5lwqhCet4Mb6OsotJgpfXonOHT_vRb0pclTnwqCs0sX-KqaX0dq17Luvuf88GGCOrx8CuAPhhzDMJCb8YlYpJvH12s1OQhD7rKbAaO0SZyqNl37o36O8S5RlPIPwN3D6ST6_ayi_gNLJPJlzbJIeVi-8QKZssUhmqvMl35fIx-kYq1ihsp0COaVdlH17N-AWS2-chtprA45lFOPCo32jgF2DEf3iNOqUhge0C0ERxigtS7JCF8xMocAf6VWn2z6jx2_Dp-axAIj0uvqTZ5ncnRzfHnU8d-yCl_KYjTwdZYbFfs4zP8_CPNSG89SEuU55FhjtJzbTuEMjeS6gGQiC5sznFqii5T43bIVMF8PCrhEaw2VmZZ4AFHPL0liHCTQkknEB4By3SFB_b5W6muR4NMajqsVnDwp9pNBHCs_LDMIW2Wv6PFcVOf60jmo3qolxpQAy_uy3WftcuVn9qiD8RVhQLREtstPchvmImyy6sMNxZQMGMpEtsloNkeY1QwmLRSbh4XJi8DQGWOt78k4x6Jc1vyOgiiJm6__8ORtkFq9KFaLYJNOjl7HdAjY1Mtuwjji72C4nzSfHzCD1 |
| linkProvider | Elsevier |
| linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Nb9QwEB2VIgQXxDcLBYzEDUV1YsdOuLFVyy6kK6S20t4sO3HarUq2gl2p3PnhzCRO1AXRA8fY4yjJjGee4zdjgHfe-tQq53BZEotIyhznXKlUpL2SznOb1p4ShQ9nanIiP8_T-Rbs9bkwRKsMvr_z6a23Di274WvuXi4WlOPLEwzuCPjRDQud3YLbiAY4mfZ0Ph62EuKMix4Dk3jInOlIXvb87JT4Xaqt4xkn_4pOf6PPP0mU16LSwQO4H-Ak-9g98UPY8s0juNMdMPnzMfz6tKYyVkRtZ4hOWUG87-gI9eLZUSBRR2MMZBUjx3DhrxgGr8WKXdMaC1TDD6xAr4hGytqarDiEUlMYAkg2mxTjKdu_Wn4bbosRkX3t_vI8gZOD_eO9SRTOXYhKmYlVZNPKiYzXsuJ1ldSJdVKWLqltKavYWZ77ytIWjZa1wmZECFYKLj1iRS-5dOIpbDfLxj8HluFl5XWdYyyWXpSZTXJsyLWQCqNzNoK4_96mDEXJ6WyMC9Ozz84N6ciQjgwdmBknI3g_jLnsSnLcKJ32ajQbhmUwZtw4bqfXuQnT-odB_5dSRbVcjeDt0I0TknZZbOOX604GBXSuR_CsM5HhMRONq0Wh8eZ6w3gGASr2vdnTLM7aot8pYkWViRf_-Tpv4O7k-LAwxXT25SXco56Wkqh2YHv1fe1fIbRaudft1PkNhEEjHw |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Guidelines+for+Large-Scale+Sequence-Based+Complex+Trait+Association+Studies%3A+Lessons+Learned+from+the+NHLBI+Exome+Sequencing+Project&rft.jtitle=American+journal+of+human+genetics&rft.au=Auer%2C+Paul+L&rft.au=Reiner%2C+Alex+P&rft.au=Wang%2C+Gao&rft.au=Kang%2C+Hyun+Min&rft.date=2016-10-06&rft.issn=1537-6605&rft.eissn=1537-6605&rft.volume=99&rft.issue=4&rft.spage=791&rft_id=info:doi/10.1016%2Fj.ajhg.2016.08.012&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0002-9297&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0002-9297&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0002-9297&client=summon |