title: Do genetic risk scores for body mass index predict risk of phobic anxiety? Evidence for a shared genetic risk factor.
abstract: BACKGROUND
  Obesity and anxiety are often linked but the direction of effects is not clear.
  
  
  METHODS
  Using genetic instrumental variable (IV) analyses in 5911 female participants from the Nurses' Health Study (NHS, initiated 1976) and 3697 male participants from the Health Professional Follow-up Study (HPFS, initiated 1986), we aimed to determine whether obesity increases symptoms of phobic anxiety. As instrumental variables we used the fat mass and obesity-associated (FTO) gene, the melanocortin 4 receptor (MC4R) gene and a genetic risk score (GRS) based on 32 single nucleotide polymorphisms (SNPs) that significantly predict body mass index (BMI). 'Functional' GRSs corresponding with specific biological pathways that shape BMI (adipogenesis, appetite and cardiopulmonary) were considered. The main outcome was phobic anxiety measured by the Crown Crisp Index (CCI) in 2004 in the NHS and in 2000 in the HPFS.
  
  
  RESULTS
  In observational analysis, a 1-unit higher BMI was associated with higher phobic anxiety symptoms [women: β = 0.05, 95% confidence interval (CI) 0.030-0.068; men: β = 0.04, 95% CI 0.016-0.071). IV analyses showed that BMI was associated with higher phobic anxiety symptoms in the FTO-instrumented analysis (p = 0.005) but not in the GRS-instrumented analysis (p = 0.256). Functional GRSs showed heterogeneous, non-significant effects of BMI on phobic anxiety symptoms.
  
  
  CONCLUSIONS
  Our findings do not provide conclusive evidence in favor of the hypothesis that higher BMI leads to higher levels of phobic anxiety, but rather suggest that genes that influence obesity, in particular FTO, may have direct effects on phobic anxiety, and hence that obesity and phobic anxiety may share common genetic determinants.
authors: Department of Social and Behavioral Sciences,Harvard School of Public Health,Boston, MA,USA.
authors: S
authors: S
authors: Walter
authors: Department of Social and Behavioral Sciences,Harvard School of Public Health,Boston, MA,USA.
authors: M M
authors: MM
authors: Glymour
authors: Mailman School of Public Health,Columbia University,New York, NY,USA.
authors: K
authors: K
authors: Koenen
authors: Department of Epidemiology,Harvard School of Public Health,Boston, MA,USA.
authors: L
authors: L
authors: Liang
authors: Department of Epidemiology,Harvard School of Public Health,Boston, MA,USA.
authors: E J
authors: EJ
authors: Tchetgen Tchetgen
authors: Department of Nutrition,Harvard School of Public Health,Boston, MA,USA.
authors: M
authors: M
authors: Cornelis
authors: Department of Social and Behavioral Sciences,Harvard School of Public Health,Boston, MA,USA.
authors: S-C
authors: SC
authors: Chang
authors: Department of Social and Behavioral Sciences,Harvard School of Public Health,Boston, MA,USA.
authors: M
authors: M
authors: Rewak
authors: Department of Epidemiology,Harvard School of Public Health,Boston, MA,USA.
authors: E
authors: E
authors: Rimm
authors: Department of Social and Behavioral Sciences,Harvard School of Public Health,Boston, MA,USA.
authors: I
authors: I
authors: Kawachi
authors: Department of Social and Behavioral Sciences,Harvard School of Public Health,Boston, MA,USA.
authors: L D
authors: LD
authors: Kubzansky
mesh_terms: D000328:Adult; D000368:Aged; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000704:Analysis of Variance; D015992:Body Mass Index; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000523:psychology*; D010698:Phobic Disorders / Q000097:blood / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology*; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics; D018570:Risk Assessment; D017678:Sex Distribution; D011795:Surveys and Questionnaires; D014481:United States / Q000453:epidemiology
chemical_list: C470072:MC4R protein, human; D011506:Proteins; D044105:Receptor, Melanocortin, Type 4; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human