Genome-wide Association Study of Platelet Count Identifies Ancestry-Specific Loci in Hispanic/Latino Americans

• Published in: American journal of human genetics Vol. 98; no. 2; pp. 229 - 242
• Main Authors: Schick, Ursula M., Jain, Deepti, Hodonsky, Chani J., Morrison, Jean V., Davis, James P., Brown, Lisa, Sofer, Tamar, Conomos, Matthew P., Schurmann, Claudia, McHugh, Caitlin P., Nelson, Sarah C., Vadlamudi, Swarooparani, Stilp, Adrienne, Plantinga, Anna, Baier, Leslie, Bien, Stephanie A., Gogarten, Stephanie M., Laurie, Cecelia A., Taylor, Kent D., Liu, Yongmei, Auer, Paul L., Franceschini, Nora, Szpiro, Adam, Rice, Ken, Kerr, Kathleen F., Rotter, Jerome I., Hanson, Robert L., Papanicolaou, George, Rich, Stephen S., Loos, Ruth J.F., Browning, Brian L., Browning, Sharon R., Weir, Bruce S., Laurie, Cathy C., Mohlke, Karen L., North, Kari E., Thornton, Timothy A., Reiner, Alex P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.02.2016; Cell Press; Elsevier
• Subjects: Actinin - genetics; Adolescent; Adult; Aged; Alleles; Blood platelets; Gene Frequency; Gene loci; Genetic Association Studies - methods; Genetic Loci; Genomes; Genotype; Genotyping Techniques; Hispanic or Latino - genetics; Humans; MEF2 Transcription Factors - genetics; Membrane Proteins - genetics; Middle Aged; Phenotype; Platelet Count; Polymorphism, Single Nucleotide; Receptors, GABA-B - genetics; Thrombosis; Young Adult
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1016/j.ajhg.2015.12.003

Platelets play an essential role in hemostasis and thrombosis. We performed a genome-wide association study of platelet count in 12,491 participants of the Hispanic Community Health Study/Study of Latinos by using a mixed-model method that accounts for admixture and family relationships. We discovered and replicated associations with five genes (ACTN1, ETV7, GABBR1-MOG, MEF2C, and ZBTB9-BAK1). Our strongest association was with Amerindian-specific variant rs117672662 (p value = 1.16 × 10−28) in ACTN1, a gene implicated in congenital macrothrombocytopenia. rs117672662 exhibited allelic differences in transcriptional activity and protein binding in hematopoietic cells. Our results underscore the value of diverse populations to extend insights into the allelic architecture of complex traits.