title: Association of genetic risk scores with body mass index in Swiss psychiatric cohorts.
abstract: OBJECTIVE
  Weight gain is associated with psychiatric disorders and/or with psychotropic drug treatments. We analyzed in three psychiatric cohorts under psychotropic treatment the association of weighted genetic risk scores (w-GRSs) with BMI by integrating BMI-related polymorphisms from the candidate-gene approach and Genome-Wide Association Studies (GWAS).
  
  
  METHODS
  w-GRS of 32 polymorphisms associated previously with BMI in general population GWAS and 20 polymorphisms associated with antipsychotics-induced weight gain were investigated in three independent psychiatric samples.
  
  
  RESULTS
  w-GRS of 32 polymorphisms were significantly associated with BMI in the psychiatric sample 1 (n=425) and were replicated in another sample (n=177). Those at the percentile 95 (p95) of the score had 2.26 and 2.99 kg/m(2) higher predicted BMI compared with individuals at the percentile 5 (p5) in sample 1 and in sample 3 (P=0.009 and 0.04, respectively). When combining all samples together (n=750), a significant difference of 1.89 kg/m(2) predicted BMI was found between p95 and p5 individuals at 12 months of treatment. Stronger associations were found among men (difference: 2.91 kg/m(2) of predicted BMI between p95 and p5, P=0.0002), whereas no association was found among women. w-GRS of 20 polymorphisms was not associated with BMI. The w-GRS of 52 polymorphisms and the clinical variables (age, sex, treatment) explained 1.99 and 3.15%, respectively, of BMI variability.
  
  
  CONCLUSIONS
  The present study replicated in psychiatric cohorts previously identified BMI risk variants obtained in GWAS analyses from population-based samples. Sex-specific analysis should be considered in further analysis.
authors.affiliation: aUnit of Pharmacogenetics and Clinical Psychopharmacology, Department of Psychiatry, Centre for Psychiatric Neuroscience bDepartment of Psychiatry, Centre of Psychiatric Epidemiology and Psychopathology cService of Old Age Psychiatry, Department of Psychiatry dService of General Psychiatry, Department of Psychiatry, Lausanne University Hospital, Prilly eDepartment of Mental Health and Psychiatry, University Hospital of Geneva fSchool of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva gInstitute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital hSwiss Institute of Bioinformatics, Lausanne, Switzerland.
authors.forename: Núria
authors.initials: N
authors.lastname: Saigi-Morgui
authors.forename: Frederik
authors.initials: F
authors.lastname: Vandenberghe
authors.forename: Aurélie
authors.initials: A
authors.lastname: Delacrétaz
authors.forename: Lina
authors.initials: L
authors.lastname: Quteineh
authors.forename: Mehdi
authors.initials: M
authors.lastname: Gholamrezaee
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Aubry
authors.forename: Armin
authors.initials: A
authors.lastname: von Gunten
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Kutalik
authors.forename: Philippe
authors.initials: P
authors.lastname: Conus
authors.forename: Chin B
authors.initials: CB
authors.lastname: Eap
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D015331:Cohort Studies; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011619:Psychotropic Drugs / Q000009:adverse effects*; D012737:Sex Factors; D013557:Switzerland; D015430:Weight Gain / Q000235:genetics*; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D011619:Psychotropic Drugs