Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Using genetic loci to understand the relationship between adiposity and psychological distress
T2 - a Mendelian Randomization study in the Copenhagen General Population Study of 53,221 adults
AU - Lawlor, Debbie A.
AU - Harbord, Roger M.
AU - Tybjaerg-Hansen, Anne
AU - Palmer, Tom M.
AU - Zacho, Jeppe
AU - Benn, Marianne
AU - Timpson, Nicholas J.
AU - Smith, George Davey
AU - Nordestgaard, Børge G.
N1 - © 2011 The Association for the Publication of the Journal of Internal Medicine.
PY - 2011/5
Y1 - 2011/5
N2 - 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.
AB - 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.
KW - Adiposity
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Anxiety Disorders
KW - Body Mass Index
KW - Cohort Studies
KW - Cross-Sectional Studies
KW - Denmark
KW - Female
KW - Genetic Loci
KW - Genotype
KW - Humans
KW - Male
KW - Mendelian Randomization Analysis
KW - Middle Aged
KW - Proteins
KW - Receptor, Melanocortin, Type 4
KW - Risk Factors
KW - Stress, Psychological
KW - Waist-Hip Ratio
KW - Young Adult
U2 - 10.1111/j.1365-2796.2011.02343.x
DO - 10.1111/j.1365-2796.2011.02343.x
M3 - Journal article
C2 - 21210875
VL - 269
SP - 525
EP - 537
JO - Journal of Internal Medicine
JF - Journal of Internal Medicine
SN - 1365-2796
IS - 5
ER -