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; 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

doi:10.1038/ncomms9442

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. ChiavacciCecilia 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

Faculty of Medicine

University of Iceland

Research output: Contribution to journal › Article › peer-review

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 language	English
Article number	8442
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms9442
Publication status	Published - 9 Oct 2015

Bibliographical note

Funding Information: We thank the patients and their families for their participation in the genotyping studies and in the Biobank Repository at the Center for Applied Genomics. We are also thankful for the contributions of the Italian IBD Group, including Cucchiara S (Roma), Lionetti P (Firenze), Barabino G (Genova), de Angelis GL (Parma), Guariso G (Padova), Catassi C (Ancona), Lombardi G (Pescara), Staiano AM (Napoli), De Venuto D (Bari), Romano C (Messina), D’incà R (Padova), Vecchi M (Milano), Andriulli A and Bossa F (S. Giovanni Rotondo). Y.R.L. is supported by the Paul and Daisy Soros Fellowship for New Americans and an NIH F30 Individual NRSA Training Grant (1F30AR066486). This study was supported by Institutional Development Funds from the Children’s Hospital of Philadelphia, and by DP3DK085708, RC1AR058606, U01HG006830, the Crohn’s and Colitis Foundation, the Juvenile Diabetes Research Foundation and a grant from the LRI to E.L.P. Publisher Copyright: © 2015 Macmillan Publishers Limited.

Access to Document

10.1038/ncomms9442

Cite this

Li, Y. R., Zhao, S. D., Li, J., Bradfield, J. P., Mohebnasab, M., Steel, L., Kobie, J., Abrams, D. J., Mentch, F. D., Glessner, J. T., Guo, Y., Wei, Z., Connolly, J. J., Cardinale, C. J., Bakay, M., Li, D., Maggadottir, S. M., Thomas, K. A., Qui, H., ... Hakonarson, H. (2015). Genetic sharing and heritability of paediatric age of onset autoimmune diseases. Nature Communications, 6, Article 8442. https://doi.org/10.1038/ncomms9442

@article{a9d0e856c9544d718a6be5d4ba78baf2,

title = "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.",

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

note = "Funding Information: We thank the patients and their families for their participation in the genotyping studies and in the Biobank Repository at the Center for Applied Genomics. We are also thankful for the contributions of the Italian IBD Group, including Cucchiara S (Roma), Lionetti P (Firenze), Barabino G (Genova), de Angelis GL (Parma), Guariso G (Padova), Catassi C (Ancona), Lombardi G (Pescara), Staiano AM (Napoli), De Venuto D (Bari), Romano C (Messina), D{\textquoteright}inc{\`a} R (Padova), Vecchi M (Milano), Andriulli A and Bossa F (S. Giovanni Rotondo). Y.R.L. is supported by the Paul and Daisy Soros Fellowship for New Americans and an NIH F30 Individual NRSA Training Grant (1F30AR066486). This study was supported by Institutional Development Funds from the Children{\textquoteright}s Hospital of Philadelphia, and by DP3DK085708, RC1AR058606, U01HG006830, the Crohn{\textquoteright}s and Colitis Foundation, the Juvenile Diabetes Research Foundation and a grant from the LRI to E.L.P. Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited.",

year = "2015",

month = oct,

day = "9",

doi = "10.1038/ncomms9442",

language = "English",

volume = "6",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

}

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

TY - JOUR

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

AU - Flatø, Berit

AU - Førre, Oystein

AU - Denson, Lee A.

AU - Thompson, Susan D.

AU - Becker, Mara L.

AU - Guthery, Stephen L.

AU - Latiano, Anna

AU - Perez, Elena

AU - Resnick, Elena

AU - Strisciuglio, Caterina

AU - Staiano, Annamaria

AU - Miele, Erasmo

AU - Silverberg, Mark S.

AU - Lie, Benedicte A.

AU - Punaro, Marilynn

AU - Russell, Richard K.

AU - Wilson, David C.

AU - Dubinsky, Marla C.

AU - Monos, Dimitri S.

AU - Annese, Vito

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.

AU - Li, Hongzhe

AU - Keating, Brendan J.

AU - Hakonarson, Hakon

N1 - Funding Information: We thank the patients and their families for their participation in the genotyping studies and in the Biobank Repository at the Center for Applied Genomics. We are also thankful for the contributions of the Italian IBD Group, including Cucchiara S (Roma), Lionetti P (Firenze), Barabino G (Genova), de Angelis GL (Parma), Guariso G (Padova), Catassi C (Ancona), Lombardi G (Pescara), Staiano AM (Napoli), De Venuto D (Bari), Romano C (Messina), D’incà R (Padova), Vecchi M (Milano), Andriulli A and Bossa F (S. Giovanni Rotondo). Y.R.L. is supported by the Paul and Daisy Soros Fellowship for New Americans and an NIH F30 Individual NRSA Training Grant (1F30AR066486). This study was supported by Institutional Development Funds from the Children’s Hospital of Philadelphia, and by DP3DK085708, RC1AR058606, U01HG006830, the Crohn’s and Colitis Foundation, the Juvenile Diabetes Research Foundation and a grant from the LRI to E.L.P. Publisher Copyright: © 2015 Macmillan Publishers Limited.

PY - 2015/10/9

Y1 - 2015/10/9

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84944245664

U2 - 10.1038/ncomms9442

DO - 10.1038/ncomms9442

M3 - Article

C2 - 26450413

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

M1 - 8442

ER -

Genetic sharing and heritability of paediatric age of onset autoimmune diseases

Abstract

Bibliographical note

Access to Document

Fingerprint

Cite this