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A versatile, fast and unbiased method for estimation of gene-by-environment interaction effects on biobank-scale datasets.


ABSTRACT: Identification of gene-by-environment interactions (GxE) is crucial to understand the interplay of environmental effects on complex traits. However, current methods evaluating GxE on biobank-scale datasets have limitations. We introduce MonsterLM, a multiple linear regression method that does not rely on model specification and provides unbiased estimates of variance explained by GxE. We demonstrate robustness of MonsterLM through comprehensive genome-wide simulations using real genetic data from 325,989 individuals. We estimate GxE using waist-to-hip-ratio, smoking, and exercise as the environmental variables on 13 outcomes (N = 297,529-325,989) in the UK Biobank. GxE variance is significant for 8 environment-outcome pairs, ranging from 0.009 - 0.071. The majority of GxE variance involves SNPs without strong marginal or interaction associations. We observe modest improvements in polygenic score prediction when incorporating GxE. Our results imply a significant contribution of GxE to complex trait variance and we show MonsterLM to be well-purposed to handle this with biobank-scale data.

SUBMITTER: Di Scipio M 

PROVIDER: S-EPMC10457310 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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A versatile, fast and unbiased method for estimation of gene-by-environment interaction effects on biobank-scale datasets.

Di Scipio Matteo M   Khan Mohammad M   Mao Shihong S   Chong Michael M   Judge Conor C   Pathan Nazia N   Perrot Nicolas N   Nelson Walter W   Lali Ricky R   Di Shuang S   Morton Robert R   Petch Jeremy J   Paré Guillaume G  

Nature communications 20230825 1


Identification of gene-by-environment interactions (GxE) is crucial to understand the interplay of environmental effects on complex traits. However, current methods evaluating GxE on biobank-scale datasets have limitations. We introduce MonsterLM, a multiple linear regression method that does not rely on model specification and provides unbiased estimates of variance explained by GxE. We demonstrate robustness of MonsterLM through comprehensive genome-wide simulations using real genetic data fro  ...[more]

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