title: Assessing the genetic overlap between BMI and cognitive function.
abstract: 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 five 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 four 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- and 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. Seven common genetic variants are significantly associated with both traits at P<5 × 10(-5), which is significantly more than expected by chance (P=0.007). All these results suggest there are shared genetic contributions to BMI and cognitive function.
authors: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.|Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia.
authors: R E
authors: RE
authors: Marioni
authors: Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia.
authors: J
authors: 0000-0003-2001-2474
authors: J
authors: Yang
authors: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors: D
authors: D
authors: Dykiert
authors: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors: R
authors: R
authors: Mõttus
authors: Generation Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
authors: A
authors: 0000-0003-0198-5078
authors: A
authors: Campbell
authors: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors: G
authors: G
authors: Davies
authors: Generation Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.|Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
authors: C
authors: C
authors: Hayward
authors: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.|Generation Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
authors: D J
authors: DJ
authors: Porteous
authors: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia.|University of Queensland Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, QLD, Australia.
authors: P M
authors: PM
authors: Visscher
authors: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.|Generation Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
authors: I J
authors: IJ
authors: Deary
mesh_terms: D000368:Aged; D015992:Body Mass Index; D003071:Cognition / Q000502:physiology*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020412:Multifactorial Inheritance / Q000235:genetics; D009765:Obesity / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012606:Scotland