Probabilistic inference of the genetic architecture underlying functional enrichment of complex traits.
Details
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State: Public
Version: author
License: CC BY 4.0
UNIL restricted access
State: Public
Version: author
License: CC BY 4.0
Serval ID
serval:BIB_9710808BCDCD
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Probabilistic inference of the genetic architecture underlying functional enrichment of complex traits.
Journal
Nature communications
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
30/11/2021
Peer-reviewed
Oui
Volume
12
Number
1
Pages
6972
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Abstract
We develop a Bayesian model (BayesRR-RC) that provides robust SNP-heritability estimation, an alternative to marker discovery, and accurate genomic prediction, taking 22 seconds per iteration to estimate 8.4 million SNP-effects and 78 SNP-heritability parameters in the UK Biobank. We find that only ≤10% of the genetic variation captured for height, body mass index, cardiovascular disease, and type 2 diabetes is attributable to proximal regulatory regions within 10kb upstream of genes, while 12-25% is attributed to coding regions, 32-44% to introns, and 22-28% to distal 10-500kb upstream regions. Up to 24% of all cis and coding regions of each chromosome are associated with each trait, with over 3,100 independent exonic and intronic regions and over 5,400 independent regulatory regions having ≥95% probability of contributing ≥0.001% to the genetic variance of these four traits. Our open-source software (GMRM) provides a scalable alternative to current approaches for biobank data.
Keywords
Bayes Theorem, Body Height, Body Mass Index, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Genetic Techniques, Genetic Variation, Genome-Wide Association Study, Genomics, Genotype, Humans, Introns, Models, Statistical, Multifactorial Inheritance/genetics, Open Reading Frames, Phenotype, Software
Pubmed
Web of science
Open Access
Yes
Create date
03/12/2021 9:55
Last modification date
27/07/2022 5:38