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Research article - Peer-reviewed, 2021

Probabilistic inference of the genetic architecture underlying functional enrichment of complex traits

Patxot, Marion; Banos, Daniel Trejo; Kousathanas, Athanasios; Orliac, Etienne J.; Ojavee, Sven E.; Moser, Gerhard; Holloway, Alexander; Sidorenko, Julia; Kutalik, Zoltan; Magi, Reedik; Visscher, Peter M.; Ronnegard, Lars; Robinson, Matthew R.


Improving inference in large-scale genetic data linked to electronic medical record data requires the development of novel computationally efficient regression methods. Here, the authors develop a Bayesian approach for association analyses to improve SNP-heritability estimation, discovery, fine-mapping and genomic prediction.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.

Published in

Nature Communications
2021, Volume: 12, number: 1, article number: 6972

    Sustainable Development Goals

    SDG3 Good health and well-being

    UKÄ Subject classification

    Bioinformatics (Computational Biology)

    Publication identifier


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