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Using genetic loci to understand the relationship between adiposity and psychological distress: a Mendelian Randomization study in the Copenhagen General Population Study of 53 221 adults
Author(s) -
Lawlor Debbie A.,
Harbord Roger M.,
TybjaergHansen Anne,
Palmer Tom M.,
Zacho Jeppe,
Benn Marianne,
Timpson Nicholas J.,
Davey Smith George,
Nordestgaard Børge G.
Publication year - 2011
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/j.1365-2796.2011.02343.x
Subject(s) - mendelian randomization , medicine , body mass index , confounding , population , distress , odds ratio , demography , clinical psychology , genetics , genetic variants , biology , environmental health , sociology , gene , genotype
. Lawlor DA, Harbord RM, Tybjaerg‐Hansen A, Palmer TM, Zacho J, Benn M, Timpson NJ, Smith GD, Nordestgaard BG (MRC Centre for Causal Analyses in Translational Epidemiology, University of Bristol, UK; The Department of Social Medicine, University of Bristol, UK; Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark; The Copenhagen General Population Study, Herlev Hospital, Copenhagen, Denmark; Copenhagen University Hospital, Faculty of Health Sciences, University of Copenhagen, Denmark; Department of Clinical Biochemistry, Herlev Hospital, Copenhagen, Denmark) Using genetic loci to understand the relationship between adiposity and psychological distress: a Mendelian Randomization study in the Copenhagen General Population Study of 53 221 adults. J Intern Med 2011; 269 : 525–537. Objective. We used genetic variants that are robustly associated with adiposity to examine the causal association of adiposity with psychological distress. Methods. We examined the association of adiposity with psychological distress in a large ( N = 53 221) general population cohort of 20‐ to 99‐year‐old adults from Copenhagen, Denmark. Psychological distress was assessed using four questions that asked about: feeling stressed; not accomplishing very much; wanting to give up; and regular use of antidepressants/sedatives. We used the genetic loci FTO rs9939609 and MC4R rs17782313 as instrumental variables for adiposity quantified by body mass index (BMI) and waist to hip ratio (WHR). Results. In conventional multivariable analyses, BMI and WHR were positively associated with distress. For example, the odds ratio of reporting not accomplishing for each additional standard deviation increase for BMI was 1.11 (95% CI: 1.09, 1.13) and for WHR was 1.10 (95% CI: 1.08, 1.13) in the fully adjusted analyses. In contrast, instrumental variable analyses showed an inverse association of adiposity on distress; corresponding odds ratio in instrumental variable analyses was 0.64 (95% CI: 0.46, 0.89) for BMI and 0.49 (95% CI: 0.25, 0.94) for WHR ( P ‐values for difference between the two approaches both = 0.001). Conclusion. The inverse associations of adiposity and psychological distress when genetic variants are used as instrumental variables could be explained by biological pathways linking adiposity and distress. The positive associations of adiposity with distress in multivariable analyses might be explained by residual confounding or reverse causality.