“Genome-Wide Association Study of Habitual Physical Activity in over 277,000 UK Biobank Participants Identifies Novel Variants and Genetic Correlations With Chronotype and Obesity-Related Traits”, 2017-08-22 (; backlinks; similar):
Physical activity (PA) protects against a wide range of diseases. Engagement in habitual PA has been shown to be heritable, motivating the search for specific genetic variants that explain variation in habitual PA and may ultimately improve efforts to promote PA and target the best type of PA for each individual.
We used data from the UK Biobank to perform the largest genome-wide association study of PA, using four measures based on self-report (n = 277,656) and accelerometry (n = 67,808). Replication was then sought in the Atherosclerosis Risk in Communities (ARIC) study (n = 8,556).
In the UK Biobank, we identified 17 genome-wide loci across the four PA measures. Interestingly, rs429358 of the APOE gene was the most strongly associated variant with any single PA measure and was at least nominally associated with 3 of the four PA measures examined. We also identified 3 loci (DNAJC1, DCAF5, and PML) consistently associated with PA across all four measures.
Tissue enrichment analyses implicate the brain and pituitary gland as locations where PA-associated loci may exert their actions. Genetic correlation analyses suggest a positive genetic correlation of PA with early-morning chronotype and psychiatric traits, and a negative genetic correlation of PA with obesity-related traits.
Using data from the GIANT consortium, we identify several loci that are associated with both increased waist circumference and decreased PA. Although very small effect sizes precluded replication of individual loci in ARIC, we found consistent overall genetic correlations of PA with other traits.
These results provide new insight into the genetic basis of habitual PA, and the genetic links connecting PA and obesity.