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Do genetic risk scores for body mass index predict risk of phobic anxiety? Evidence for a shared genetic risk factor

Published online by Cambridge University Press:  28 May 2014

S. Walter ,
M. M. Glymour ,
K. Koenen ,
L. Liang ,
E. J. Tchetgen Tchetgen ,
M. Cornelis ,
S.-C. Chang ,
M. Rewak ,
E. Rimm  and
I. Kawachi
...Show all authors
S. Walter*
Affiliation:
Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, MA, USA Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA
M. M. Glymour
Affiliation:
Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, MA, USA Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA
K. Koenen
Affiliation:
Mailman School of Public Health, Columbia University, New York, NY, USA
L. Liang
Affiliation:
Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA
E. J. Tchetgen Tchetgen
Affiliation:
Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA
M. Cornelis
Affiliation:
Department of Nutrition, Harvard School of Public Health, Boston, MA, USA
S.-C. Chang
Affiliation:
Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, MA, USA
M. Rewak
Affiliation:
Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, MA, USA
E. Rimm
Affiliation:
Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA Department of Nutrition, Harvard School of Public Health, Boston, MA, USA
I. Kawachi
Affiliation:
Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, MA, USA
L. D. Kubzansky
Affiliation:
Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, MA, USA
*
*Address for correspondence: S. Walter, Ph.D., Department of Social and Behavioral Sciences, Harvard School of Public Health, Landmark Center, 445-C, 401 Park Drive, Boston, MA 02215, USA. (Email: [email protected])
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Abstract

Background

Obesity and anxiety are often linked but the direction of effects is not clear.

Method

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.

Keywords

Anxietybody mass indexFTOgeneticsMendelian randomization analysisphobic anxiety
Type
Original Articles
Information
Psychological Medicine , Volume 45 , Issue 1 , January 2015 , pp. 181 - 191
Copyright
Copyright © Cambridge University Press 2014 

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