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Molecular genetic contributions to self-rated health.

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.

SUBMITTER: Harris SE

PROVIDER: S-EPMC5837683 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Molecular genetic contributions to self-rated health.

Harris Sarah E SE Hagenaars Saskia P SP Davies Gail G David Hill W W Liewald David C M DCM Ritchie Stuart J SJ Marioni Riccardo E RE Sudlow Cathie L M CLM Wardlaw Joanna M JM McIntosh Andrew M AM Gale Catharine R CR Deary Ian J IJ

International journal of epidemiology 20170601 3

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 27864402

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Project description:Self-reported tiredness and low energy, often called fatigue, are associated with poorer physical and mental health. Twin studies have indicated that this has a heritability between 6 and 50%. In the UK Biobank sample (N=108 976), we carried out a genome-wide association study (GWAS) of responses to the question, 'Over the last two weeks, how often have you felt tired or had little energy?' Univariate GCTA-GREML found that the proportion of variance explained by all common single-nucleotide polymorphisms for this tiredness question was 8.4% (s.e.=0.6%). GWAS identified one genome-wide significant hit (Affymetrix id 1:64178756_C_T; P=1.36 × 10-11). Linkage disequilibrium score regression and polygenic profile score analyses were used to test for shared genetic aetiology between tiredness and up to 29 physical and mental health traits from GWAS consortia. Significant genetic correlations were identified between tiredness and body mass index (BMI), C-reactive protein, high-density lipoprotein (HDL) cholesterol, forced expiratory volume, grip strength, HbA1c, longevity, obesity, self-rated health, smoking status, triglycerides, type 2 diabetes, waist-hip ratio, attention deficit hyperactivity disorder, bipolar disorder, major depressive disorder, neuroticism, schizophrenia and verbal-numerical reasoning (absolute rg effect sizes between 0.02 and 0.78). Significant associations were identified between tiredness phenotypic scores and polygenic profile scores for BMI, HDL cholesterol, low-density lipoprotein cholesterol, coronary artery disease, C-reactive protein, HbA1c, height, obesity, smoking status, triglycerides, type 2 diabetes, waist-hip ratio, childhood cognitive ability, neuroticism, bipolar disorder, major depressive disorder and schizophrenia (standardised β's had absolute values<0.03). These results suggest that tiredness is a partly heritable, heterogeneous and complex phenomenon that is phenotypically and genetically associated with affective, cognitive, personality and physiological processes.

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Molecular genetic contributions to self-rated health.

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Molecular genetic contributions to self-rated health.

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