Fine mapping in the MHC region accounts for 18% additional genetic risk for celiac disease

Javier Gutierrez-Achury; Alexandra Zhernakova; Sara L Pulit; Gosia Trynka; Karen A Hunt; Jihane Romanos; Soumya Raychaudhuri; David A van Heel; Cisca Wijmenga; Paul I W de Bakker

doi:10.1038/ng.3268

Fine mapping in the MHC region accounts for 18% additional genetic risk for celiac disease

Javier Gutierrez-Achury, Alexandra Zhernakova, Sara L Pulit, Gosia Trynka, Karen A Hunt, Jihane Romanos, Soumya Raychaudhuri, David A van Heel, Cisca Wijmenga, Paul I W de Bakker

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

Abstract

Although dietary gluten is the trigger for celiac disease, risk is strongly influenced by genetic variation in the major histocompatibility complex (MHC) region. We fine mapped the MHC association signal to identify additional risk factors independent of the HLA-DQA1 and HLA-DQB1 alleles and observed five new associations that account for 18% of the genetic risk. Taking these new loci together with the 57 known non-MHC loci, genetic variation can now explain up to 48% of celiac disease heritability.

Original language	English
Pages (from-to)	577-8
Number of pages	2
Journal	Nature Genetics
Volume	47
Issue number	6
DOIs	https://doi.org/10.1038/ng.3268
Publication status	Published - Jun 2015

Keywords

Case-Control Studies
Celiac Disease
Chromosome Mapping
Genetic Association Studies
Genetic Predisposition to Disease
HLA-DQ alpha-Chains
HLA-DQ beta-Chains
Haplotypes
Humans
Risk
Risk Factors

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title = "Fine mapping in the MHC region accounts for 18% additional genetic risk for celiac disease",

abstract = "Although dietary gluten is the trigger for celiac disease, risk is strongly influenced by genetic variation in the major histocompatibility complex (MHC) region. We fine mapped the MHC association signal to identify additional risk factors independent of the HLA-DQA1 and HLA-DQB1 alleles and observed five new associations that account for 18% of the genetic risk. Taking these new loci together with the 57 known non-MHC loci, genetic variation can now explain up to 48% of celiac disease heritability.",

keywords = "Case-Control Studies, Celiac Disease, Chromosome Mapping, Genetic Association Studies, Genetic Predisposition to Disease, HLA-DQ alpha-Chains, HLA-DQ beta-Chains, Haplotypes, Humans, Risk, Risk Factors",

author = "Javier Gutierrez-Achury and Alexandra Zhernakova and Pulit, {Sara L} and Gosia Trynka and Hunt, {Karen A} and Jihane Romanos and Soumya Raychaudhuri and {van Heel}, {David A} and Cisca Wijmenga and {de Bakker}, {Paul I W}",

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month = jun,

doi = "10.1038/ng.3268",

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T1 - Fine mapping in the MHC region accounts for 18% additional genetic risk for celiac disease

AU - Gutierrez-Achury, Javier

AU - Zhernakova, Alexandra

AU - Pulit, Sara L

AU - Trynka, Gosia

AU - Hunt, Karen A

AU - Romanos, Jihane

AU - Raychaudhuri, Soumya

AU - van Heel, David A

AU - Wijmenga, Cisca

AU - de Bakker, Paul I W

PY - 2015/6

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AB - Although dietary gluten is the trigger for celiac disease, risk is strongly influenced by genetic variation in the major histocompatibility complex (MHC) region. We fine mapped the MHC association signal to identify additional risk factors independent of the HLA-DQA1 and HLA-DQB1 alleles and observed five new associations that account for 18% of the genetic risk. Taking these new loci together with the 57 known non-MHC loci, genetic variation can now explain up to 48% of celiac disease heritability.

KW - Case-Control Studies

KW - Celiac Disease

KW - Chromosome Mapping

KW - Genetic Association Studies

KW - Genetic Predisposition to Disease

KW - HLA-DQ alpha-Chains

KW - HLA-DQ beta-Chains

KW - Haplotypes

KW - Humans

KW - Risk

KW - Risk Factors

U2 - 10.1038/ng.3268

DO - 10.1038/ng.3268

M3 - Article

C2 - 25894500

SN - 1061-4036

VL - 47

SP - 577

EP - 578

JO - Nature Genetics

JF - Nature Genetics

IS - 6

ER -

Fine mapping in the MHC region accounts for 18% additional genetic risk for celiac disease

Abstract

Keywords

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