Please use this identifier to cite or link to this item: http://hdl.handle.net/10668/2317
Título : A genetic risk score combining 32 SNPs is associated with body mass index and improves obesity prediction in people with major depressive disorder.
Autor : Hung, Chi-Fa
Breen, Gerome
Czamara, Darina
Corre, Tanguy
Wolf, Christiane
Kloiber, Stefan
Bergmann, Sven
Craddock, Nick
Gill, Michael
Holsboer, Florian
Jones, Lisa
Jones, Ian
Korszun, Ania
Kutalik, Zoltan
Lucae, Susanne
Maier, Wolfgang
Mors, Ole
Owen, Michael J
Rice, John
Rietschel, Marcella
Uher, Rudolf
Vollenweider, Peter
Waeber, Gerard
Craig, Ian W
Farmer, Anne E
Lewis, Cathryn M
Müller-Myhsok, Bertram
Preisig, Martin
McGuffin, Peter
Rivera, Margarita
Filiación: [Hung,CF; Breen,G; Uher,R; Craig,IW; Farmer,AE; Lewis,CM; McGuffin,P; Rivera,M] MRC SGDP Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London ,London, UK. [Hung,CF] Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Taiwan. [Breen,G] National Institute for Health Research Biomedical Research Centre for Mental Health at the Maudsley and Institute of Psychiatry, King’s College London, London, UK. [Czamara,D; Wolf,C; Kloiber,S; Holsboer,F; Lucae,S; Müller-Myhsok,B] Max-Planck-Institute of Psychiatry, Munich, Germany. [Corre,T; Bergmann,S; Kutalik,Z]Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier, Universitaire Vaudois (CHUV), Lausanne, Switzerland. [Bergmann,S; Kutalik,Z] Swiss Institute of Bioinformatics Lausanne, Switzerland. [Craddock,N; Jones,I] MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, UK. [Gill,M] Department of Psychiatry, Trinity Centre for Health Sciences Dublin, Ireland. [Jones,L] Department of Psychiatry, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK. [Korszun,A] Barts and The London School of Medicine and Dentistry, Queen Mary’s University of London London, UK. [Maier,W] Department of Psychiatry, University of Bonn, Bonn, Germany. [Mors,O] Research Department P, Aarhus University Hospital Skovagervej, Risskov, Denmark. [Owen,MJ] MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, UK. [Rice,J] Department of Psychiatry, Washington University School of Medicine St Louis, MO, USA. [Rietschel1,M] Central Institute of Mental Health, Mannheim, Germany. [Uher,R] Department of Psychiatry, Dalhousie University, Halifax Nova Scotia, Canada. [Vollenweider,P; d Waeber,G] Division of Internal Medicine, Lausanne, Switzerland. [Lewis,CM] Department of Medical and Molecular Genetics, School of Medicine, King’s College London, Guys Hospital, London UK. [Preisig,M ]Department of Psychiatry, Lausanne University Hospital, Prilly-Lausanne, Switzerland. [Rivera,M] CIBERSAM-University of Granada and Institute of Neurosciences Federico Olóriz, Centro de Investigación Biomédica, University of Granada, Armilla Granada, Spain. Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain.
Palabras clave : Body mass index
Genetic risk score
Major depressive disorder
Obesity
Área bajo la curva
Índice de masa corporal
Estudios de casos y controles
Trastorno depresivo mayor
Estudio de asociación del genoma completo
Modelos logísticos
Obesidad
Polimorfismo de nucleótido simple
Curva ROC
Riesgo
MeSH: Medical Subject Headings::Named Groups::Persons::Age Groups::Adult::Aged
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Area Under Curve
Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Mass Index
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies
Medical Subject Headings::Psychiatry and Psychology::Mental Disorders::Mood Disorders::Depressive Disorder::Depressive Disorder, Major
Medical Subject Headings::Check Tags::Female
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Genetic Association Studies::Genome-Wide Association Study
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Check Tags::Male
Medical Subject Headings::Check Tags::Male
Medical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Sensitivity and Specificity::ROC Curve
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk
Medical Subject Headings::Named Groups::Persons::Age Groups::Adult
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Logistic Models
Fecha de publicación : 17-Apr-2015
Editorial : BioMed Central
Cita Bibliográfica: Hung CF, Breen G, Czamara D, Corre T, Wolf C, Kloiber S, et al. A genetic risk score combining 32 SNPs is associated with body mass index and improves obesity prediction in people with major depressive disorder. BMC Med. 2015; 13:86
Abstract: BACKGROUND Obesity is strongly associated with major depressive disorder (MDD) and various other diseases. Genome-wide association studies have identified multiple risk loci robustly associated with body mass index (BMI). In this study, we aimed to investigate whether a genetic risk score (GRS) combining multiple BMI risk loci might have utility in prediction of obesity in patients with MDD. METHODS Linear and logistic regression models were conducted to predict BMI and obesity, respectively, in three independent large case-control studies of major depression (Radiant, GSK-Munich, PsyCoLaus). The analyses were first performed in the whole sample and then separately in depressed cases and controls. An unweighted GRS was calculated by summation of the number of risk alleles. A weighted GRS was calculated as the sum of risk alleles at each locus multiplied by their effect sizes. Receiver operating characteristic (ROC) analysis was used to compare the discriminatory ability of predictors of obesity. RESULTS In the discovery phase, a total of 2,521 participants (1,895 depressed patients and 626 controls) were included from the Radiant study. Both unweighted and weighted GRS were highly associated with BMI (P < 0.001) but explained only a modest amount of variance. Adding 'traditional' risk factors to GRS significantly improved the predictive ability with the area under the curve (AUC) in the ROC analysis, increasing from 0.58 to 0.66 (95% CI, 0.62-0.68; χ(2) = 27.68; P < 0.0001). Although there was no formal evidence of interaction between depression status and GRS, there was further improvement in AUC in the ROC analysis when depression status was added to the model (AUC = 0.71; 95% CI, 0.68-0.73; χ(2) = 28.64; P <0.0001). We further found that the GRS accounted for more variance of BMI in depressed patients than in healthy controls. Again, GRS discriminated obesity better in depressed patients compared to healthy controls. We later replicated these analyses in two independent samples (GSK-Munich and PsyCoLaus) and found similar results. CONCLUSIONS A GRS proved to be a highly significant predictor of obesity in people with MDD but accounted for only modest amount of variance. Nevertheless, as more risk loci are identified, combining a GRS approach with information on non-genetic risk factors could become a useful strategy in identifying MDD patients at higher risk of developing obesity.
Descripción : Journal Article; Research Support, Non-U.S. Gov't;
URI: http://hdl.handle.net/10668/2317
Versión del editor : http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-015-0334-3#Abs1
DOI: 10.1186/s12916-015-0334-3
ISSN : 1741-7015 (Online)
Appears in Collections:01- Artículos - ibsGRANADA. Instituto de Investigación Biosanitaria de Granada
01- Artículos - Complejo Hospitalario Universitario de Granada

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