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

Li, Yun R and Zhao, Sihai D and Li, Jin and Bradfield, Jonathan P and Mohebnasab, Maede and Steel, Laura and Kobie, Julie and Abrams, Debra J and Mentch, Frank D and Glessner, Joseph T and Guo, Yiran and Wei, Zhi and Connolly, John J and Cardinale, Christopher J and Bakay, Marina and Li, Dong and Maggadottir, S Melkorka and Thomas, Kelly A and Qui, Haijun and Chiavacci, Rosetta M and Kim, Cecilia E and Wang, Fengxiang and Snyder, James and Flatø, Berit and Førre, Øystein and Denson, Lee A and Thompson, Susan D and Becker, Mara L and Guthery, Stephen L and Latiano, Anna and Perez, Elena and Resnick, Elena and Strisciuglio, Caterina and Staiano, Annamaria and Miele, Erasmo and Silverberg, Mark S and Lie, Benedicte A and Punaro, Marilynn and Russell, Richard K and Wilson, David C and Dubinsky, Marla C and Monos, Dimitri S and Annese, Vito and Munro, Jane E and Wise, Carol and Chapel, Helen and Cunningham-Rundles, Charlotte and Orange, Jordan S and Behrens, Edward M and Sullivan, Kathleen E and Kugathasan, Subra and Griffiths, Anne M and Satsangi, Jack and Grant, Struan FA and Sleiman, Patrick MA and Finkel, Terri H and Polychronakos, Constantin and Baldassano, Robert N and Luning Prak, Eline T and Ellis, Justine A and Li, Hongzhe and Keating, Brendan J and Hakonarson, Hakon (2015) Genetic sharing and heritability of paediatric age of onset autoimmune diseases. Nat Commun, 6. 8442 - ?.

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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.

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Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Li, Yun R Zhao, Sihai D Li, Jin Bradfield, Jonathan P Mohebnasab, Maede MAM1236@pitt.edu MAM1236 0000-0001-6623-9514 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 FA Sleiman, Patrick MA Finkel, Terri H Polychronakos, Constantin Baldassano, Robert N Luning Prak, Eline T Ellis, Justine A Li, Hongzhe Keating, Brendan J Hakonarson, Hakon
Date:	21 August 2015
Date Type:	Acceptance
Journal or Publication Title:	Nat Commun
Volume:	6
Page Range:	8442 - ?
DOI or Unique Handle:	10.1038/ncomms9442
Schools and Programs:	School of Medicine > Pathology
Refereed:	Yes
Uncontrolled Keywords:	Adolescent, Age of Onset, Autoimmune Diseases, Case-Control Studies, Child, Child, Preschool, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Polymorphism, Single Nucleotide, White People
Funders:	NIAMS NIH HHS (RC1 AR058606), Medical Research Council (G0800675), Medical Research Council (G0600329), MRF (MRF_C0482), Chief Scientist Office (ETM/137), Chief Scientist Office (ETM/75), NIAMS NIH HHS (RC1AR058606), NIAID NIH HHS (P01 AI061093), NIAMS NIH HHS (P30 AR070549), NIAID NIH HHS (R18 AI048693), NCATS NIH HHS (UL1 TR001425), NIAMS NIH HHS (F30 AR066486), NIAMS NIH HHS (1F30AR066486), NHGRI NIH HHS (U01HG006830), NIDDK NIH HHS (DP3 DK085708), Medical Research Council (G0800759), NIAMS NIH HHS (P30 AR047363), NIDDK NIH HHS (DP3DK085708), NICHD NIH HHS (R01 HD052973), NHGRI NIH HHS (U01 HG006830)
Date Deposited:	29 Aug 2022 17:06
Last Modified:	21 Mar 2023 20:55
URI:	http://d-scholarship.pitt.edu/id/eprint/43677

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