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Molecular genetic contributions to self-rated health.

TitleMolecular genetic contributions to self-rated health.
Publication TypeJournal Article
Year of Publication2017
AuthorsHarris SE, Hagenaars SP, Davies G, W Hill D, Liewald DCM, Ritchie SJ, Marioni RE, Sudlow CLM, Wardlaw JM, McIntosh AM, Gale CR
Secondary AuthorsDeary IJ
Corporate AuthorsMETASTROKE Consortium, International Consortium for Blood Pressure Genome-Wide Association Studies, International Consortium for Blood Pressure Genome-Wide Association Studies, CHARGE Consortium Aging and Longevity Group, CHARGE Consortium Cognitive Group
JournalInt J Epidemiol
Volume46
Issue3
Pagination994-1009
Date Published2017 06 01
ISSN1464-3685
KeywordsAdult, Aged, Diagnostic Self Evaluation, Female, Health Status, Humans, Linkage Disequilibrium, Male, Middle Aged, Molecular Epidemiology, Mortality, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Quantitative Trait, Heritable, United Kingdom
Abstract

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 up to 60% and that its genetic architecture may overlap with 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 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.

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 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.

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.

DOI10.1093/ije/dyw219
Alternate JournalInt J Epidemiol
PubMed ID27864402
PubMed Central IDPMC5837683
Grant ListMC_UP_A620_1015 / / Medical Research Council / United Kingdom
MC_U147585827 / / Medical Research Council / United Kingdom
MC_UU_12011/2 / / Medical Research Council / United Kingdom
/ / Biotechnology and Biological Sciences Research Council / United Kingdom
MC_U147585819 / / Medical Research Council / United Kingdom
MR/K026992/1 / / Medical Research Council / United Kingdom
MC_UP_A620_1014 / / Medical Research Council / United Kingdom
104036/Z/14/Z / / Wellcome Trust / United Kingdom
MC_UU_12011/1 / / Medical Research Council / United Kingdom
G0400491 / / Medical Research Council / United Kingdom
MC_U147585824 / / Medical Research Council / United Kingdom