title: Molecular genetic contributions to self-rated health.
abstract: Poorer self-rated health (SRH) predicts worse health outcomes, even when adjusted for objective measures of disease at time of rating. Twin studies indicate SRH has a heritability of up to 60% and that its genetic architecture may overlap with that of personality and cognition.
  
  
  
  We carried out a genome-wide association study (GWAS) of SRH on 111 749 members of the UK Biobank sample. Univariate genome-wide complex trait analysis (GCTA)-GREML analyses were used to estimate the proportion of variance explained by all common autosomal single nucleotide polymorphisms (SNPs) for SRH. Linkage disequilibrium (LD) score regression and polygenic risk scoring, two complementary methods, were used to investigate pleiotropy between SRH in the UK Biobank and up to 21 health-related and personality and cognitive traits from published GWAS consortia.
  
  
  
  The GWAS identified 13 independent signals associated with SRH, including several in regions previously associated with diseases or disease-related traits. The strongest signal was on chromosome 2 (rs2360675, P = 1.77 x 10 -10 ) close to KLF7 . A second strong peak was identified on chromosome 6 in the major histocompatibility region (rs76380179, P = 6.15 x 10 -10 ). The proportion of variance in SRH that was explained by all common genetic variants was 13%. Polygenic scores for the following traits and disorders were associated with SRH: cognitive ability, education, neuroticism, body mass index (BMI), longevity, attention-deficit hyperactivity disorder (ADHD), major depressive disorder, schizophrenia, lung function, blood pressure, coronary artery disease, large vessel disease stroke and type 2 diabetes.
  
  
  
  Individual differences in how people respond to a single item on SRH are partly explained by their genetic propensity to many common psychiatric and physical disorders and psychological traits.
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Medical Genetics Section, University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Edinburgh, UK.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Harris
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology.|Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
authors.forename: Saskia P
authors.initials: SP
authors.lastname: Hagenaars
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology.
authors.forename: Gail
authors.initials: G
authors.lastname: Davies
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology.
authors.forename: W
authors.initials: W
authors.lastname: David Hill
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology.
authors.forename: David C M
authors.initials: DCM
authors.lastname: Liewald
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Ritchie
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Medical Genetics Section, University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Edinburgh, UK.|Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia.
authors.forename: Riccardo E
authors.initials: RE
authors.lastname: Marioni
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Medical Genetics Section, University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Edinburgh, UK.|Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: Cathie L M
authors.initials: CLM
authors.lastname: Sudlow
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Wardlaw
authors.affiliation: Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: McIntosh
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology.|MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
authors.forename: Catharine R
authors.initials: CR
authors.lastname: Gale
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Deary
mesh_terms: D000328:Adult; D000368:Aged; D059026:Diagnostic Self Evaluation; D005260:Female; D006304:Health Status; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology / Q000379:methods* / Q000706:statistics & numerical data*; D009026:Mortality / Q000639:trends; D020412:Multifactorial Inheritance; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable; D006113:United Kingdom
keywords: Self-rated health; genetic correlation; genome-wide association study; heritability; pleiotropy; polygenic score