title: Shared genetic aetiology between cognitive functions and physical and mental health in UK Biobank (N=112 151) and 24 GWAS consortia.
abstract: Causes of the well-documented association between low levels of cognitive functioning and many adverse neuropsychiatric outcomes, poorer physical health and earlier death remain unknown. We used linkage disequilibrium regression and polygenic profile scoring to test for shared genetic aetiology between cognitive functions and neuropsychiatric disorders and physical health. Using information provided by many published genome-wide association study consortia, we created polygenic profile scores for 24 vascular-metabolic, neuropsychiatric, physiological-anthropometric and cognitive traits in the participants of UK Biobank, a very large population-based sample (N=112 151). Pleiotropy between cognitive and health traits was quantified by deriving genetic correlations using summary genome-wide association study statistics and to the method of linkage disequilibrium score regression. Substantial and significant genetic correlations were observed between cognitive test scores in the UK Biobank sample and many of the mental and physical health-related traits and disorders assessed here. In addition, highly significant associations were observed between the cognitive test scores in the UK Biobank sample and many polygenic profile scores, including coronary artery disease, stroke, Alzheimer's disease, schizophrenia, autism, major depressive disorder, body mass index, intracranial volume, infant head circumference and childhood cognitive ability. Where disease diagnosis was available for UK Biobank participants, we were able to show that these results were not confounded by those who had the relevant disease. These findings indicate that a substantial level of pleiotropy exists between cognitive abilities and many human mental and physical health disorders and traits and that it can be used to predict phenotypic variance across samples.
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.|Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
authors.forename: S P
authors.initials: SP
authors.lastname: Hagenaars
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Medical Genetics Section, Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.
authors.forename: S E
authors.initials: SE
authors.lastname: Harris
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: G
authors.initials: G
authors.lastname: Davies
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: W D
authors.initials: WD
authors.lastname: Hill
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: D C M
authors.initials: DC
authors.lastname: Liewald
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Ritchie
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Medical Genetics Section, Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.|Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
authors.forename: R E
authors.initials: RE
authors.lastname: Marioni
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: C
authors.initials: C
authors.lastname: Fawns-Ritchie
authors.affiliation: Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
authors.forename: B
authors.initials: B
authors.lastname: Cullen
authors.affiliation: Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Malik
authors.affiliation: Department of Neurology, University of Virginia, Charlottesville, VA, USA.|Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
authors.forename: B B
authors.initials: BB
authors.lastname: Worrall
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Medical Genetics Section, Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.|Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: C L M
authors.initials: CL
authors.lastname: Sudlow
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Wardlaw
authors.affiliation: Department of Psychiatry, University of Oxford, Oxford, UK.
authors.forename: J
authors.initials: J
authors.lastname: Gallacher
authors.affiliation: Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
authors.forename: J
authors.initials: J
authors.lastname: Pell
authors.affiliation: Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: McIntosh
authors.affiliation: Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Smith
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.|MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
authors.forename: C R
authors.initials: CR
authors.lastname: Gale
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: I J
authors.initials: IJ
authors.lastname: Deary
mesh_terms: D000328:Adult; D000368:Aged; D018070:Biological Specimen Banks; D003071:Cognition / Q000502:physiology; D016208:Databases, Factual; D005260:Female; D056726:Genetic Association Studies / Q000379:methods*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods; D006262:Health; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008603:Mental Health; D008875:Middle Aged; D020412:Multifactorial Inheritance / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
references.citation: Biol Psychiatry. 2013 May 15;73(10):938-43
references.pmid: 23419543
references.citation: Nat Genet. 2015 Jul;47(7):702-9
references.pmid: 25985137
references.citation: J Alzheimers Dis. 2014;39(3):565-74
references.pmid: 24246418
references.citation: Int J Epidemiol. 2011 Jun;40(3):626-44
references.pmid: 21037248
references.citation: J Epidemiol Community Health. 1998 Mar;52(3):153-60
references.pmid: 9616419
references.citation: Int J Epidemiol. 2010 Oct;39(5):1362-9
references.pmid: 20504860
references.citation: Nature. 2009 Aug 6;460(7256):748-52
references.pmid: 19571811
references.citation: Lancet Respir Med. 2015 Oct;3(10):769-81
references.pmid: 26423011
references.citation: Nat Rev Cardiol. 2010 Dec;7(12):686-98
references.pmid: 20978471
references.citation: Mol Psychiatry. 2016 Mar;21(3):419-25
references.pmid: 25754080
references.citation: Br J Psychiatry. 2010 Feb;196(2):109-15
references.pmid: 20118454
references.citation: Mol Psychiatry. 2015 Feb;20(1):98-108
references.pmid: 25224258
references.citation: Bioinformatics. 2015 May 1;31(9):1466-8
references.pmid: 25550326
references.citation: Nat Rev Endocrinol. 2011 Feb;7(2):108-14
references.pmid: 21263438
references.citation: Nat Genet. 2015 Mar;47(3):291-5
references.pmid: 25642630
references.citation: Nat Genet. 2015 Nov;47(11):1236-41
references.pmid: 26414676
references.citation: Int J Epidemiol. 2016 Feb;45(1):178-85
references.pmid: 26213105
references.citation: Epidemiology. 2010 Jan;21(1):70-7
references.pmid: 19907333
references.citation: Nat Neurosci. 2015 Jul;18(7):953-5
references.pmid: 26053403
references.citation: Nat Rev Genet. 2013 Jul;14(7):483-95
references.pmid: 23752797
references.citation: Gerontology. 2012;58(6):545-53
references.pmid: 22907506
references.citation: Diabet Med. 2014 Jun;31(6):714-20
references.pmid: 24344862
references.citation: Proc Natl Acad Sci U S A. 2014 Sep 23;111(38):13790-4
references.pmid: 25201988
references.citation: PLoS Med. 2015 Mar 31;12(3):e1001779
references.pmid: 25826379
references.citation: Psychol Sci Public Interest. 2010 Aug;11(2):53-79
references.pmid: 26168413
references.citation: Mol Psychiatry. 2016 Sep;21(9):1188-93
references.pmid: 26303664
references.citation: Neurology. 2016 Feb 16;86(7):611-8
references.pmid: 26695942