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

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Pysyväisosoite

http://hdl.handle.net/10138/340126

Lähdeviite

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

Julkaisun nimi: Independent and cumulative coeliac disease-susceptibility loci are associated with distinct disease phenotypes
Tekijä: Cerqueira, Juliana X. M.; Saavalainen, Päivi; Kurppa, Kalle; Laurikka, Pilvi; Huhtala, Heini; Nykter, Matti; Koskinen, Lotta L. E.; Yohannes, Dawit A.; Kilpeläinen, Elina; Shcherban, Anastasia; Palotie, Aarno; Kaukinen, Katri; Lindfors, Katri
Tekijän organisaatio: Immunomics
Department of Medical and Clinical Genetics
University of Helsinki
Research Programme of Molecular Medicine
Research Programs Unit
TRIMM - Translational Immunology Research Program
Genomics of Neurological and Neuropsychiatric Disorders
Institute for Molecular Medicine Finland
Centre of Excellence in Complex Disease Genetics
Aarno Palotie / Principal Investigator
Päiväys: 2021-06
Kieli: eng
Sivumäärä: 11
Kuuluu julkaisusarjaan: Journal of Human Genetics
ISSN: 1434-5161
DOI-tunniste: https://doi.org/10.1038/s10038-020-00888-5
URI: http://hdl.handle.net/10138/340126
Tiivistelmä: 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.
Avainsanat: GENOME-WIDE ASSOCIATION
MULTIPLE COMMON
POPULATION
VARIANTS
LINKAGE
RISK
3111 Biomedicine
1184 Genetics, developmental biology, physiology
Vertaisarvioitu: Kyllä
Tekijänoikeustiedot: cc_by
Pääsyrajoitteet: openAccess
Rinnakkaistallennettu versio: publishedVersion


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