Molecular genetic contributions to self-rated health

Harris, S. E., Hagenaars, S. P., Davies, G., David Hill, W., Liewald, D. C., Ritchie, S. J., Marioni, R. E., Sudlow, C. L., Wardlaw, J. M., McIntosh, A. M., Gale, C. R. and Deary, I. J. (2016) Molecular genetic contributions to self-rated health. International Journal of Epidemiology, 46 3: 994-1009. doi:10.1093/ije/dyw219


Author Harris, S. E.
Hagenaars, S. P.
Davies, G.
David Hill, W.
Liewald, D. C.
Ritchie, S. J.
Marioni, R. E.
Sudlow, C. L.
Wardlaw, J. M.
McIntosh, A. M.
Gale, C. R.
Deary, I. J.
Title Molecular genetic contributions to self-rated health
Journal name International Journal of Epidemiology   Check publisher's open access policy
ISSN 0300-5771
1464-3685
Publication date 2016-11-17
Sub-type Article (original research)
DOI 10.1093/ije/dyw219
Open Access Status DOI
Volume 46
Issue 3
Start page 994
End page 1009
Total pages 36
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
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.
Formatted 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.
Keyword Self-rated health
genetic correlation
genome-wide association study
heritability
pleiotropy
polygenic score
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID MC_UP_A620_1015
MC_UU_12011/2
MR/K026992/1
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
 
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Created: Wed, 01 Mar 2017, 12:19:55 EST by Kirstie Asmussen on behalf of School of Music