Genetic sharing and heritability of paediatric age of onset autoimmune diseases

Yun R. Li, Sihai D. Zhao, Jin Li, Jonathan P. Bradfield, Maede Mohebnasab, Laura Steel, Julie Kobie, Debra J. Abrams, Frank D. Mentch, Joseph T. Glessner, Yiran Guo, Zhi Wei, John J. Connolly, Christopher J. Cardinale, Marina Bakay, Dong Li, S. Melkorka Maggadottir, Kelly A. Thomas, Haijun Qui, Rosetta M. Chiavacci & 43 others Cecilia E. Kim, Fengxiang Wang, James Snyder, Berit Flatø, Oystein Førre, Lee A. Denson, Susan D. Thompson, Mara L. Becker, Stephen L. Guthery, Anna Latiano, Elena Perez, Elena Resnick, Caterina Strisciuglio, Annamaria Staiano, Erasmo Miele, Mark S. Silverberg, Benedicte A. Lie, Marilynn Punaro, Richard K. Russell, David C. Wilson, Marla C. Dubinsky, Dimitri S. Monos, Vito Annese, Jane E. Munro, Carol Wise, Helen Chapel, Charlotte Cunningham-Rundles, Jordan S. Orange, Edward M. Behrens, Kathleen E. Sullivan, Subra Kugathasan, Anne M. Griffiths, Jack Satsangi, Struan F A Grant, Patrick M A Sleiman, Terri H. Finkel, Constantin Polychronakos, Robert N. Baldassano, Eline T. Luning Prak, Justine A. Ellis, Hongzhe Li, Brendan J. Keating, Hakon Hakonarson

Research output: Contribution to journalArticle

27 Citations (Scopus)

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.

Original languageEnglish
Article number8442
JournalNature Communications
Volume6
DOIs
Publication statusPublished - Oct 9 2015

Fingerprint

Pediatrics
Age of Onset
Autoimmune Diseases
Single Nucleotide Polymorphism
Genome-Wide Association Study
Population
Western hemisphere
estimates
partitions
therapy
Therapeutics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Li, Y. R., Zhao, S. D., Li, J., Bradfield, J. P., Mohebnasab, M., Steel, L., ... Hakonarson, H. (2015). Genetic sharing and heritability of paediatric age of onset autoimmune diseases. Nature Communications, 6, [8442]. https://doi.org/10.1038/ncomms9442

Genetic sharing and heritability of paediatric age of onset autoimmune diseases. / 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, Oystein; 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.

In: Nature Communications, Vol. 6, 8442, 09.10.2015.

Research output: Contribution to journalArticle

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, O, 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 2015, 'Genetic sharing and heritability of paediatric age of onset autoimmune diseases', Nature Communications, vol. 6, 8442. https://doi.org/10.1038/ncomms9442
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, Oystein ; 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. / Genetic sharing and heritability of paediatric age of onset autoimmune diseases. In: Nature Communications. 2015 ; Vol. 6.
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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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T1 - Genetic sharing and heritability of paediatric age of onset autoimmune diseases

AU - Li, Yun R.

AU - Zhao, Sihai D.

AU - Li, Jin

AU - Bradfield, Jonathan P.

AU - Mohebnasab, Maede

AU - Steel, Laura

AU - Kobie, Julie

AU - Abrams, Debra J.

AU - Mentch, Frank D.

AU - Glessner, Joseph T.

AU - Guo, Yiran

AU - Wei, Zhi

AU - Connolly, John J.

AU - Cardinale, Christopher J.

AU - Bakay, Marina

AU - Li, Dong

AU - Maggadottir, S. Melkorka

AU - Thomas, Kelly A.

AU - Qui, Haijun

AU - Chiavacci, Rosetta M.

AU - Kim, Cecilia E.

AU - Wang, Fengxiang

AU - Snyder, James

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AU - Førre, Oystein

AU - Denson, Lee A.

AU - Thompson, Susan D.

AU - Becker, Mara L.

AU - Guthery, Stephen L.

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AU - Perez, Elena

AU - Resnick, Elena

AU - Strisciuglio, Caterina

AU - Staiano, Annamaria

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AU - Munro, Jane E.

AU - Wise, Carol

AU - Chapel, Helen

AU - Cunningham-Rundles, Charlotte

AU - Orange, Jordan S.

AU - Behrens, Edward M.

AU - Sullivan, Kathleen E.

AU - Kugathasan, Subra

AU - Griffiths, Anne M.

AU - Satsangi, Jack

AU - Grant, Struan F A

AU - Sleiman, Patrick M A

AU - Finkel, Terri H.

AU - Polychronakos, Constantin

AU - Baldassano, Robert N.

AU - Luning Prak, Eline T.

AU - Ellis, Justine A.

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AU - Keating, Brendan J.

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