RT Journal Article
SR Electronic
T1 Molecular genetic contributions to self-rated health
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 029504
DO 10.1101/029504
A1 Sarah E Harris
A1 Saskia P Hagenaars
A1 Gail Davies
A1 W David Hill
A1 David CM Liewald
A1 Stuart J Ritchie
A1 Riccardo E Marioni
A1 METASTROKE consortium
A1 International Consortium for Blood Pressure
A1 CHARGE consortium Aging and Longevity Group
A1 CHARGE consortium Cognitive Group
A1 Cathie LM Sudlow
A1 Joanna M Wardlaw
A1 Andrew M McIntosh
A1 Catharine R Gale
A1 Ian J Deary
YR 2015
UL http://biorxiv.org/content/early/2015/10/20/029504.abstract
AB Background 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 18-60% and that its genetic architecture may overlap that of personality and cognition.Methods We carried out a genome-wide association study (GWAS) of SRH on 111 749 members of the UK Biobank sample. Univariate GCTA-GREML analyses were used to estimate the proportion of variance explained by all common autosomal SNPs for SRH. LD score regression and polygenic risk scoring were used to investigate pleiotropy between SRH in UK Biobank and up to 21 health-related and personality and cognitive traits from published GWAS consortia.Results 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 = 1.77×10−10) close to KLF7, which has previously been associated with obesity and type 2 diabetes. A second strong peak was identified on chromosome 6 in the major histocompatibility region (rs76380179, p = 6.15×10−10). 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, BMI, longevity, ADHD, major depressive disorder, schizophrenia, lung function, blood pressure, coronary artery disease, large vessel disease stroke, and type 2 diabetes.Conclusions 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.Key MessagesGenetic variants associated with common diseases and psychological traits are associated with self-rated health.The SNP-based heritability of self-rated health is 0.13 (SE 0.006).There is pleiotropy between self-rated health and psychiatric and physical diseases and psychological traits.