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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Li, YR; Zhao, SD; Li, J; Bradfield, JP; Mohebnasab, M; Steel, L; Kobie, J; Abrams, DJ; Mentch, FD; Glessner, JT; Guo, Y; Wei, Z; Connolly, JJ; Cardinale, CJ; Bakay, M; Li, D; Maggadottir, SM; Thomas, KA; Qui, H; Chiavacci, RM; Kim, CE; Wang, F; Snyder, J; Flatø, B; Førre, Ø; Denson, LA; Thompson, SD; Becker, ML; Guthery, SL; Latiano, A; Perez, E; Resnick, E; Strisciuglio, C; Staiano, A; Miele, E; Silverberg, MS; Lie, BA; Punaro, M; Russell, RK; Wilson, DC; Dubinsky, MC; Monos, DS; Annese, V; Munro, JE; Wise, C; Chapel, H; Cunningham-Rundles, C; Orange, JS; Behrens, EM; Sullivan, KE; Kugathasan, S; Griffiths, AM; Satsangi, J; Grant, SFA; Sleiman, PMA; Finkel, TH; Polychronakos, C; Baldassano, RN; Luning Prak, ET; Ellis, JA; Li, H; Keating, BJ; Hakonarson, H

Duke Contributors

Published Date

  • October 9, 2015

Published In

Volume / Issue

  • 6 /

Start / End Page

  • 8442 -

PubMed ID

  • 26450413

Pubmed Central ID

  • PMC4633631

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/ncomms9442


  • eng

Conference Location

  • England