Genetic sharing and heritability of paediatric age of onset autoimmune diseases

• Published in: Nature communications Vol. 6; no. 1; p. 8442
• Main Authors: Li, Yun R., Zhao, Sihai D., Li, Jin, Bradfield, Jonathan P., Mohebnasab, Maede, Steel, Laura, Kobie, Julie, Abrams, Debra J., Mentch, Frank D., Glessner, Joseph T., Guo, Yiran, Wei, Zhi, Connolly, John J., Cardinale, Christopher J., Bakay, Marina, Li, Dong, Maggadottir, S. Melkorka, Thomas, Kelly A., Qui, Haijun, Chiavacci, Rosetta M., Kim, Cecilia E., Wang, Fengxiang, Snyder, James, Flatø, Berit, Førre, Øystein, Denson, Lee A., Thompson, Susan D., Becker, Mara L., Guthery, Stephen L., Latiano, Anna, Perez, Elena, Resnick, Elena, Strisciuglio, Caterina, Staiano, Annamaria, Miele, Erasmo, Silverberg, Mark S., Lie, Benedicte A., Punaro, Marilynn, Russell, Richard K., Wilson, David C., Dubinsky, Marla C., Monos, Dimitri S., Annese, Vito, Munro, Jane E., Wise, Carol, Chapel, Helen, Cunningham-Rundles, Charlotte, Orange, Jordan S., Behrens, Edward M., Sullivan, Kathleen E., Kugathasan, Subra, Griffiths, Anne M., Satsangi, Jack, Grant, Struan F. A., Sleiman, Patrick M. A., Finkel, Terri H., Polychronakos, Constantin, Baldassano, Robert N., Luning Prak, Eline T., Ellis, Justine A., Li, Hongzhe, Keating, Brendan J., Hakonarson, Hakon
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.10.2015; Nature Publishing Group; Nature Pub. Group
• Subjects: 38/39; 631/208/2489/144; 692/699/249/1313; 692/700/1720; Adolescent; Age of Onset; Autoimmune diseases; Autoimmune Diseases - congenital; Autoimmune Diseases - genetics; Case-Control Studies; Child; Child, Preschool; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humanities and Social Sciences; Humans; Male; multidisciplinary; Polymorphism, Single Nucleotide; Risk sharing; Science; Science (multidisciplinary); White People - genetics
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms9442

Autoimmune diseases (AIDs) are polygenic diseases affecting 7–10% of the population in the Western Hemisphere with few effective therapies. Here, we quantify the heritability of paediatric AIDs (pAIDs), including JIA, SLE, CEL, T1D, UC, CD, PS, SPA and CVID, attributable to common genomic variations (SNP -h 2 ). SNP- h 2 estimates are most significant for T1D (0.863±s.e. 0.07) and JIA (0.727±s.e. 0.037), more modest for UC (0.386±s.e. 0.04) and CD (0.454±0.025), largely consistent with population estimates and are generally greater than that previously reported by adult GWAS. On pairwise analysis, we observed that the diseases UC-CD (0.69±s.e. 0.07) and JIA-CVID (0.343±s.e. 0.13) are the most strongly correlated. Variations across the MHC strongly contribute to SNP -h 2 in T1D and JIA, but does not significantly contribute to the pairwise rG . Together, our results partition contributions of shared versus disease-specific genomic variations to pAID heritability, identifying pAIDs with unexpected risk sharing, while recapitulating known associations between autoimmune diseases previously reported in adult cohorts. Autoimmune diseases are genetically complex disorders that affect up to 10% of the Western population. Here Li et al . quantify the heritability of a range of autoimmune diseases in the largest paediatric cohort examined to date, illustrating that genetic and non-genetic components variably contribute to the susceptibility of each disease.