Independent and cumulative coeliac disease-susceptibility loci are associated with distinct disease phenotypes

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dc.contributor.author Cerqueira, Juliana X. M.
dc.contributor.author Saavalainen, Päivi
dc.contributor.author Kurppa, Kalle
dc.contributor.author Laurikka, Pilvi
dc.contributor.author Huhtala, Heini
dc.contributor.author Nykter, Matti
dc.contributor.author Koskinen, Lotta L. E.
dc.contributor.author Yohannes, Dawit A.
dc.contributor.author Kilpeläinen, Elina
dc.contributor.author Shcherban, Anastasia
dc.contributor.author Palotie, Aarno
dc.contributor.author Kaukinen, Katri
dc.contributor.author Lindfors, Katri
dc.date.accessioned 2022-02-11T13:17:01Z
dc.date.available 2022-02-11T13:17:01Z
dc.date.issued 2021-06
dc.identifier.citation Cerqueira , J X M , Saavalainen , P , Kurppa , K , Laurikka , P , Huhtala , H , Nykter , M , Koskinen , L L E , Yohannes , D A , Kilpeläinen , E , Shcherban , A , Palotie , A , Kaukinen , K & Lindfors , K 2021 , ' Independent and cumulative coeliac disease-susceptibility loci are associated with distinct disease phenotypes ' , Journal of Human Genetics , vol. 66 , no. 6 , pp. 613-623 . https://doi.org/10.1038/s10038-020-00888-5
dc.identifier.other PURE: 160833094
dc.identifier.other PURE UUID: e15b125a-b53b-4602-ad4e-b31d41727280
dc.identifier.other WOS: 000607769400001
dc.identifier.other ORCID: /0000-0002-2527-5874/work/108067332
dc.identifier.uri http://hdl.handle.net/10138/340126
dc.description.abstract The phenotype of coeliac disease varies considerably for incompletely understood reasons. We investigated whether established coeliac disease susceptibility variants (SNPs) are individually or cumulatively associated with distinct phenotypes. We also tested whether a polygenic risk score (PRS) based on genome-wide associated (GWA) data could explain the phenotypic variation. The phenotypic association of 39 non-HLA coeliac disease SNPs was tested in 625 thoroughly phenotyped coeliac disease patients and 1817 controls. To assess their cumulative effects a weighted genetic risk score (wGRS39) was built, and stratified by tertiles. In our PRS model in cases, we took the summary statistics from the largest GWA study in coeliac disease and tested their association at eight P value thresholds (P-T) with phenotypes. Altogether ten SNPs were associated with distinct phenotypes after correction for multiple testing (P-EMP2 1.62 for having coeliac disease-related symptoms during childhood, a more severe small bowel mucosal damage, malabsorption and anaemia. PRS was associated only with dermatitis herpetiformis (P-T = 0.2, P-EMP2 = 0.02). Independent coeliac disease-susceptibility loci are associated with distinct phenotypes, suggesting that genetic factors play a role in determining the disease presentation. Moreover, the increased number of coeliac disease susceptibility SNPs might predispose to a more severe disease course. en
dc.format.extent 11
dc.language.iso eng
dc.relation.ispartof Journal of Human Genetics
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject GENOME-WIDE ASSOCIATION
dc.subject MULTIPLE COMMON
dc.subject POPULATION
dc.subject VARIANTS
dc.subject LINKAGE
dc.subject RISK
dc.subject 3111 Biomedicine
dc.subject 1184 Genetics, developmental biology, physiology
dc.title Independent and cumulative coeliac disease-susceptibility loci are associated with distinct disease phenotypes en
dc.type Article
dc.contributor.organization Immunomics
dc.contributor.organization Department of Medical and Clinical Genetics
dc.contributor.organization University of Helsinki
dc.contributor.organization Research Programme of Molecular Medicine
dc.contributor.organization Research Programs Unit
dc.contributor.organization TRIMM - Translational Immunology Research Program
dc.contributor.organization Genomics of Neurological and Neuropsychiatric Disorders
dc.contributor.organization Institute for Molecular Medicine Finland
dc.contributor.organization Centre of Excellence in Complex Disease Genetics
dc.contributor.organization Aarno Palotie / Principal Investigator
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1038/s10038-020-00888-5
dc.relation.issn 1434-5161
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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