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Genetic variation in CADM2 as a link between psychological traits and obesity
Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland.
Univ Glasgow, Coll Med Vet & Life Sci, Sch Life Sci, Glasgow, Lanark, Scotland.
Univ Milan, Dept Med Biotechnol & Translat Med, Milan, Italy;IRCCS, Ctr Cardiol Monzino, Milan, Italy.
Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland.
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 7339Article in journal (Refereed) Published
Abstract [en]

CADM2 has been associated with a range of behavioural and metabolic traits, including physical activity, risk-taking, educational attainment, alcohol and cannabis use and obesity. Here, we set out to determine whether CADM2 contributes to mechanisms shared between mental and physical health disorders. We assessed genetic variants in the CADM2 locus for association with phenotypes in the UK Biobank, IMPROVE, PROCARDIS and SCARFSHEEP studies, before performing meta-analyses. A wide range of metabolic phenotypes were meta-analysed. Psychological phenotypes analysed in UK Biobank only were major depressive disorder, generalised anxiety disorder, bipolar disorder, neuroticism, mood instability and risk-taking behaviour. In UK Biobank, four, 88 and 172 genetic variants were significantly (p < 1 x 10(-5)) associated with neuroticism, mood instability and risk-taking respectively. In meta-analyses of 4 cohorts, we identified 362, 63 and 11 genetic variants significantly (p < 1 x 10(-5)) associated with BMI, SBP and CRP respectively. Genetic effects on BMI, CRP and risk-taking were all positively correlated, and were consistently inversely correlated with genetic effects on SBP, mood instability and neuroticism. Conditional analyses suggested an overlap in the signals for physical and psychological traits. Many significant variants had genotype-specific effects on CADM2 expression levels in adult brain and adipose tissues. CADM2 variants influence a wide range of both psychological and metabolic traits, suggesting common biological mechanisms across phenotypes via regulation of CADM2 expression levels in adipose tissue. Functional studies of CADM2 are required to fully understand mechanisms connecting mental and physical health conditions.

Place, publisher, year, edition, pages
2019. Vol. 9, article id 7339
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Medical Genetics
Identifiers
URN: urn:nbn:se:uu:diva-387288DOI: 10.1038/s41598-019-43861-9ISI: 000467839800010PubMedID: 31089183OAI: oai:DiVA.org:uu-387288DiVA, id: diva2:1329124
Funder
AstraZenecaSwedish Research Council, 8691Knut and Alice Wallenberg FoundationSwedish Foundation for Strategic Research Available from: 2019-06-24 Created: 2019-06-24 Last updated: 2019-06-24Bibliographically approved

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