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Genetic sharing and heritability of paediatric age of onset autoimmune diseases.


ABSTRACT: 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.

SUBMITTER: Li YR 

PROVIDER: S-EPMC4633631 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Genetic sharing and heritability of paediatric age of onset autoimmune diseases.

Li Yun R YR   Zhao Sihai D SD   Li Jin J   Bradfield Jonathan P JP   Mohebnasab Maede M   Steel Laura L   Kobie Julie J   Abrams Debra J DJ   Mentch Frank D FD   Glessner Joseph T JT   Guo Yiran Y   Wei Zhi Z   Connolly John J JJ   Cardinale Christopher J CJ   Bakay Marina M   Li Dong D   Maggadottir S Melkorka SM   Thomas Kelly A KA   Qui Haijun H   Chiavacci Rosetta M RM   Kim Cecilia E CE   Wang Fengxiang F   Snyder James J   Flatø Berit B   Førre Øystein Ø   Denson Lee A LA   Thompson Susan D SD   Becker Mara L ML   Guthery Stephen L SL   Latiano Anna A   Perez Elena E   Resnick Elena E   Strisciuglio Caterina C   Staiano Annamaria A   Miele Erasmo E   Silverberg Mark S MS   Lie Benedicte A BA   Punaro Marilynn M   Russell Richard K RK   Wilson David C DC   Dubinsky Marla C MC   Monos Dimitri S DS   Annese Vito V   Munro Jane E JE   Wise Carol C   Chapel Helen H   Cunningham-Rundles Charlotte C   Orange Jordan S JS   Behrens Edward M EM   Sullivan Kathleen E KE   Kugathasan Subra S   Griffiths Anne M AM   Satsangi Jack J   Grant Struan F A SFA   Sleiman Patrick M A PMA   Finkel Terri H TH   Polychronakos Constantin C   Baldassano Robert N RN   Luning Prak Eline T ET   Ellis Justine A JA   Li Hongzhe H   Keating Brendan J BJ   Hakonarson Hakon H  

Nature communications 20151009


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  ...[more]

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