Discovery of novel eGFR-associated multiple independent signals using a quasi-adaptive method.
SNP-specific alpha-level
colocalization
conditional association analysis
estimated glomerular filtration rate (eGFR)
expression quantitative trait loci (eQTL)
genome-wide association studies (GWAS)
Journal
Frontiers in genetics
ISSN: 1664-8021
Titre abrégé: Front Genet
Pays: Switzerland
ID NLM: 101560621
Informations de publication
Date de publication:
2022
2022
Historique:
received:
18
07
2022
accepted:
13
10
2022
entrez:
17
11
2022
pubmed:
18
11
2022
medline:
18
11
2022
Statut:
epublish
Résumé
A decreased estimated glomerular filtration rate (eGFR) leading to chronic kidney disease is a significant public health problem. Kidney function is a heritable trait, and recent application of genome-wide association studies (GWAS) successfully identified multiple eGFR-associated genetic loci. To increase statistical power for detecting independent associations in GWAS loci, we improved our recently developed quasi-adaptive method estimating SNP-specific alpha levels for the conditional analysis, and applied it to the GWAS meta-analysis results of eGFR among 783,978 European-ancestry individuals. Among known eGFR loci, we revealed 19 new independent association signals that were subsequently replicated in the United Kingdom Biobank (n = 408,608). These associations have remained undetected by conditional analysis using the established conservative genome-wide significance level of 5 × 10
Identifiants
pubmed: 36386835
doi: 10.3389/fgene.2022.997302
pii: 997302
pmc: PMC9660290
doi:
Types de publication
Journal Article
Langues
eng
Pagination
997302Subventions
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Informations de copyright
Copyright © 2022 Ghasemi, Becker, Grabe and Teumer.
Déclaration de conflit d'intérêts
HG has received travel grants and speakers honoraria from Fresenius Medical Care, Neuraxpharm, Servier and Janssen Cilag as well as research funding from Fresenius Medical Care not related to the current project. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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