Genetic variation in CADM2 as a link between psychological traits and obesity

Autor: Daniel J. Smith, Laura M. Lyall, Keira J.A. Johnston, Angela Silveira, Bruna Gigante, Joey Ward, Amy Ferguson, Hugh Watkins, Bengt Sennblad, Anuj Goel, Philippe Giral, Fabrizio Veglia, Breda Cullen, Damiano Baldassarre, Steve E. Humphries, Julia Morris, Anders Hamsten, Elena Tremoli, Donald M. Lyall, Rona J. Strawbridge, Ulf de Faire, Nicholas Graham, Mark E.S. Bailey, Andries J. Smit
Přispěvatelé: University of Glasgow, Università degli Studi di Milano [Milano] (UNIMI), Centro Cardiologico Monzino [Milano], Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), The Institute of Environmental Medicine [Stockholm] (IMM), Karolinska Institutet [Stockholm], Service d’Endocrinologie, Métabolisme et Prévention des Risques Cardio-Vasculaires [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Radcliffe Department of Medicine [Oxford], University of Oxford [Oxford], The Wellcome Trust Centre for Human Genetics [Oxford], University College of London [London] (UCL), University of Edinburgh, Stockholm Bioinformatics Center (SBC), Stockholm University, Uppsala University, University Medical Center Groningen [Groningen] (UMCG), University of Groningen [Groningen], Groningen Kidney Center (GKC)
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Bipolar Disorder
[SDV]Life Sciences [q-bio]
Obesity/genetics
LOCI
lcsh:Medicine
Genome-wide association study
Bioinformatics
0302 clinical medicine
Genetics research
lcsh:Science
RISK
Multidisciplinary
Bipolar Disorder/genetics
Endocrine system and metabolic diseases
Middle Aged
Neuroticism
Anxiety Disorders
3. Good health
INSIGHTS
Cardiovascular diseases
Medical genetics
Major depressive disorder
Female
Cell Adhesion Molecules/genetics
Depressive Disorder
Major/genetics
Medical Genetics
EXPRESSION
medicine.medical_specialty
Quantitative Trait Loci
Quantitative trait locus
Biology
Polymorphism
Single Nucleotide
Article
03 medical and health sciences
Risk-Taking
[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Genetic variation
medicine
Humans
Genetic Predisposition to Disease
Bipolar disorder
Obesity
GENOME-WIDE ASSOCIATION
COMMON
METAANALYSIS
Medicinsk genetik
Aged
[SDV.GEN]Life Sciences [q-bio]/Genetics
Depressive Disorder
Major
ENERGY HOMEOSTASIS
lcsh:R
Genetic Variation
medicine.disease
BODY-MASS INDEX
Affect
030104 developmental biology
VISUALIZATION
lcsh:Q
Psychiatric disorders
Anxiety Disorders/genetics
Cell Adhesion Molecules
030217 neurology & neurosurgery
Zdroj: Scientific Reports, Vol 9, Iss 1, Pp 1-14 (2019)
Scientific Reports
Scientific Reports, Nature Publishing Group, 2019, 9 (1), ⟨10.1038/s41598-019-43861-9⟩
Scientific Reports, 9:7339. Nature Publishing Group
Morris, J, Bailey, M E S, Baldassarre, D, Cullen, B, de Faire, U, Ferguson, A, Gigante, B, Giral, P, Goel, A, Graham, N, Hamsten, A, Humphries, S E, Johnston, K J A, Lyall, D M, Lyall, L M, Sennblad, B, Silveira, A, Smit, A J, Tremoli, E, Veglia, F, Ward, J, Watkins, H, Smith, D J & Strawbridge, R J 2019, ' Genetic variation in CADM2 as a link between psychological traits and obesity ', Scientific Reports, vol. 9, no. 1, pp. 7339 . https://doi.org/10.1038/s41598-019-43861-9
ISSN: 2045-2322
Popis: 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 −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 −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.
Databáze: OpenAIRE
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