Search

We show that genotype-by-environment interaction can be inferred from an analysis without environmental data in a large sample., Genotype-by-environment interaction (GEI) is a fundamental component in understanding complex trait variation. However, it remains challenging to identify genetic variants with GEI effects in humans largely because of the small effect sizes and the difficulty of monitoring environmental fluctuations. Here, we demonstrate that GEI can be inferred from genetic variants associated with phenotypic variability in a large sample without the need of measuring environmental factors. We performed a genome-wide variance quantitative trait locus (vQTL) analysis of ~5.6 million variants on 348,501 unrelated individuals of European ancestry for 13 quantitative traits in the UK Biobank and identified 75 significant vQTLs with P < 2.0 × 10−9 for 9 traits, especially for those related to obesity. Direct GEI analysis with five environmental factors showed that the vQTLs were strongly enriched with GEI effects. Our results indicate pervasive GEI effects for obesity-related traits and demonstrate the detection of GEI without environmental data.

The evolutionary changes that occur over a small number of generations in natural populations often run counter to what is expected on the basis of the heritability of traits and the selective forces acting upon them. In Soay sheep, dark coat color is associated with large size, which is heritable and positively correlated with fitness, yet the frequency of dark sheep has decreased. This unexpected microevolutionary trend is explained by genetic linkage between the causal mutation underlying the color polymorphism and quantitative trait loci with antagonistic effects on size and fitness. As a consequence, homozygous dark sheep are large, but have reduced fitness relative to phenotypically indistinguishable dark heterozygotes and light sheep. This result demonstrates the importance of understanding the genetic basis of fitness variation when making predictions about the microevolutionary consequences of selection.