Journal
AMERICAN JOURNAL OF EPIDEMIOLOGY
Volume 173, Issue 4, Pages 421-429Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/aje/kwq444
Keywords
anxiety; body mass index; depression; Mendelian randomization analysis; mental health; obesity; risk factors
Categories
Funding
- Medical Research Council (MRC)
- British Heart Foundation
- United Kingdom Health and Safety Executive
- United Kingdom Department of Health
- US National Heart, Lung, and Blood Institute [HL36310]
- US National Institute on Aging [AG13196]
- US Agency for Health Care Policy and Research [HS06516]
- John D. and Catherine T. MacArthur Foundation Research Networks on Successful Midlife Development and Socio-economic Status and Health
- University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, cross-council Lifelong Health and Wellbeing Initiative [G0700704/84698]
- Biotechnology and Biological Sciences Research Council
- Engineering and Physical Sciences Research Council
- Economic and Social Research Council
- Chief Scientist Office of the Scottish Government Health Directorates
- Academy of Finland
- European Union
- Bupa Foundation
- European Science Foundation
- MRC [MC_U130059821, G0902037] Funding Source: UKRI
- British Heart Foundation [RG/07/008/23674] Funding Source: researchfish
- Medical Research Council [MC_U130059821, G0100222, G8802774, G19/35, G0902037] Funding Source: researchfish
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The Mendelian randomization approach exploits genetic variants to improve causal inference when using observational data. The authors examined the relation between long-term obesity and common mental disorders (CMD) by utilizing the known relation between fat mass and obesity-associated (FTO) genotype and body mass index (BMI; weight (kg)/height (m)(2)). Data collection in 2,981 men and 1,164 women (mean age at baseline = 44 years) from the Whitehall II Study (London, United Kingdom) included 4 repeated examinations of BMI and CMD over a 19-year follow-up period (1985-2004), plus an assessment of FTO polymorphism rs1421085. In men, there was an association of FTO genotype with all measures of adiposity (mean BMI, number of times obese, and, in nonobese persons, number of times overweight). FTO was also associated with CMD in men. This was independent of adiposity, thus potentially violating the exclusion restriction assumption. According to both conventional and FTO-instrumented regression analysis, measurement of obesity was associated with an increased occurrence of CMD. In the FTO-instrumented analysis only, higher BMI and overweight were also associated with CMD. In women, there was no link between FTO and adiposity. Mendelian randomization analyses supported the status of long-term obesity as a risk factor for CMD in men-a finding that should be interpreted cautiously because the function of the FTO gene is unknown.
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