Trans-ancestry, Bayesian meta-analysis discovers 20 novel risk loci for inflammatory bowel disease in an African American, East Asian and European cohort.
Humans
Bayes Theorem
Black or African American
Colitis, Ulcerative
/ genetics
Crohn Disease
/ genetics
East Asian People
Genetic Predisposition to Disease
Genome-Wide Association Study
Inflammatory Bowel Diseases
/ genetics
Membrane Proteins
/ genetics
OX40 Ligand
/ genetics
Polymorphism, Single Nucleotide
Tumor Necrosis Factor Ligand Superfamily Member 15
/ genetics
European People
Journal
Human molecular genetics
ISSN: 1460-2083
Titre abrégé: Hum Mol Genet
Pays: England
ID NLM: 9208958
Informations de publication
Date de publication:
19 02 2023
19 02 2023
Historique:
received:
24
02
2022
revised:
19
10
2022
accepted:
25
10
2022
pubmed:
30
10
2022
medline:
25
2
2023
entrez:
29
10
2022
Statut:
ppublish
Résumé
Inflammatory bowel disease (IBD) is an immune-mediated chronic intestinal disorder with major phenotypes: ulcerative colitis (UC) and Crohn's disease (CD). Multiple studies have identified over 240 IBD susceptibility loci. However, most studies have centered on European (EUR) and East Asian (EAS) populations. The prevalence of IBD in non-EUR, including African Americans (AAs), has risen in recent years. Here we present the first attempt to identify loci in AAs using a trans-ancestry Bayesian approach (MANTRA) accounting for heterogeneity between diverse ancestries while allowing for the similarity between closely related populations. We meta-analyzed genome-wide association studies (GWAS) and Immunochip data from a 2015 EUR meta-analysis of 38 155 IBD cases and 48 485 controls and EAS Immunochip study of 2824 IBD cases and 3719 controls, and our recent AA IBD GWAS of 2345 cases and 5002 controls. Across the major IBD phenotypes, we found significant evidence for 92% of 205 loci lead SNPs from the 2015 meta-analysis, but also for three IBD loci only established in latter studies. We detected 20 novel loci, all containing immunity-related genes or genes with other evidence for IBD or immune-mediated disease relevance: PLEKHG5;TNFSFR25 (encoding death receptor 3, receptor for TNFSF15 gene product TL1A), XKR6, ELMO1, BC021024;PI4KB;PSMD4 and APLP1 for IBD; AUTS2, XKR6, OSER1, TET2;AK094561, BCAP29 and APLP1 for CD; and GABBR1;MOG, DQ570892, SPDEF;ILRUN, SMARCE1;CCR7;KRT222;KRT24;KRT25, ANKS1A;TCP11, IL7, LRRC18;WDFY4, XKR6 and TNFSF4 for UC. Our study highlights the value of combining low-powered genomic studies from understudied populations of diverse ancestral backgrounds together with a high-powered study to enable novel locus discovery, including potentially important therapeutic IBD gene targets.
Identifiants
pubmed: 36308435
pii: 6779977
doi: 10.1093/hmg/ddac269
pmc: PMC9941836
doi:
Substances chimiques
BCAP29 protein, human
0
Membrane Proteins
0
OX40 Ligand
0
SMARCE1 protein, human
0
TNFSF15 protein, human
0
TNFSF4 protein, human
0
Tumor Necrosis Factor Ligand Superfamily Member 15
0
Types de publication
Meta-Analysis
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
873-882Subventions
Organisme : NIDDK NIH HHS
ID : U01 DK062431
Pays : United States
Informations de copyright
© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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