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Genetic contributions to self-reported tiredness

Genetic contributions to self-reported tiredness
Genetic contributions to self-reported tiredness

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 r g 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.

1359-4184
609-620
Deary, V.
5b5e2231-fa6c-4f1a-b533-40a76ab968c8
Hagenaars, S.P.
f5bef8aa-aeef-44bf-be77-43a1dd2dac9d
Harris, S.E.
35314bf1-25c2-4b28-acb8-5e074d8115a2
Hill, W.D.
d875efa3-58c0-4f75-a8e8-effcc937a17f
Davies, G.
4942af8c-b4c9-491c-a3a8-030baf7f94bc
Liewald, D.C.M.
6b53302f-51ea-42e7-a797-c425d867a9d9
McIntosh, A.M.
b95a091e-f188-4a64-826e-99b6c079f69a
Gale, C.R.
5bb2abb3-7b53-42d6-8aa7-817e193140c8
Deary, I.J.
14b88084-7a90-44e4-9da9-1a332b7afafb
International Consortium For Blood Pressure Gwas
Charge Consortium Aging And Longevity Group
CHARGE Consortium Inflammation Group
Deary, V.
5b5e2231-fa6c-4f1a-b533-40a76ab968c8
Hagenaars, S.P.
f5bef8aa-aeef-44bf-be77-43a1dd2dac9d
Harris, S.E.
35314bf1-25c2-4b28-acb8-5e074d8115a2
Hill, W.D.
d875efa3-58c0-4f75-a8e8-effcc937a17f
Davies, G.
4942af8c-b4c9-491c-a3a8-030baf7f94bc
Liewald, D.C.M.
6b53302f-51ea-42e7-a797-c425d867a9d9
McIntosh, A.M.
b95a091e-f188-4a64-826e-99b6c079f69a
Gale, C.R.
5bb2abb3-7b53-42d6-8aa7-817e193140c8
Deary, I.J.
14b88084-7a90-44e4-9da9-1a332b7afafb

Deary, V., Hagenaars, S.P., Harris, S.E., Hill, W.D., Davies, G., Liewald, D.C.M., McIntosh, A.M., Gale, C.R. and Deary, I.J. , International Consortium For Blood Pressure Gwas, Charge Consortium Aging And Longevity Group and CHARGE Consortium Inflammation Group (2018) Genetic contributions to self-reported tiredness. Molecular Psychiatry, 23 (3), 609-620. (doi:10.1038/mp.2017.5).

Record type: Article

Abstract

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 r g 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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Accepted/In Press date: 13 December 2016
e-pub ahead of print date: 14 February 2017
Published date: 1 March 2018

Identifiers

Local EPrints ID: 418415
URI: https://eprints.soton.ac.uk/id/eprint/418415
ISSN: 1359-4184
PURE UUID: 08755e12-3dfc-4964-ae9f-a41f7a1cb910
ORCID for C.R. Gale: ORCID iD orcid.org/0000-0002-3361-8638

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Date deposited: 08 Mar 2018 17:30
Last modified: 03 Dec 2019 02:01

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