“Assessing the Genetic Overlap between BMI and Cognitive Function”, 2016 (; backlinks):
Obesity and low cognitive function are associated with multiple adverse health outcomes across the life course. They have a small phenotypic correlation (r = −0.11; high body mass index (BMI)-low cognitive function), but whether they have a shared genetic aetiology is unknown.
We investigated the phenotypic and genetic correlations between the traits using data from 6815 unrelated, genotyped members of Generation Scotland, an ethnically homogeneous cohort from 5 sites across Scotland. Genetic correlations were estimated using the following: same-sample bivariate genome-wide complex trait analysis (GCTA)-GREML; independent samples bivariate GCTA-GREML using Generation Scotland for cognitive data and 4 other samples (n = 20 806) for BMI; and bivariate LDSC analysis using the largest genome-wide association study (GWAS) summary data on cognitive function (n = 48,462) and BMI (n = 339,224) to date. The GWAS summary data were also used to create polygenic scores for the two traits, with within & cross-trait prediction taking place in the independent Generation Scotland cohort.
A large genetic correlation of −0.51 (s.e. 0.15) was observed using the same-sample GCTA-GREML approach compared with −0.10 (s.e. 0.08) from the independent-samples GCTA-GREML approach and −0.22 (s.e. 0.03) from the bivariate LDSC analysis.
A genetic profile score using cognition-specific genetic variants accounts for 0.08% (p = 0.020) of the variance in BMI and a genetic profile score using BMI-specific variants accounts for 0.42% (p = 1.9 × 10−7) of the variance in cognitive function. 7 common genetic variants are statistically-significantly associated with both traits at p < 5 × 10−5, which is statistically-significantly more than expected by chance (p = 0.007).
All these results suggest there are shared genetic contributions to BMI and cognitive function.