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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

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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. / Lawlor, Debbie A.; Harbord, Roger M.; Tybjaerg-Hansen, Anne et al.
In: Journal of Internal Medicine, Vol. 269, No. 5, 05.2011, p. 525-537.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Lawlor, DA, Harbord, RM, Tybjaerg-Hansen, A, Palmer, TM, Zacho, J, Benn, M, Timpson, NJ, Smith, GD & Nordestgaard, BG 2011, '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', Journal of Internal Medicine, vol. 269, no. 5, pp. 525-537. https://doi.org/10.1111/j.1365-2796.2011.02343.x

APA

Lawlor, D. A., Harbord, R. M., Tybjaerg-Hansen, A., Palmer, T. M., Zacho, J., Benn, M., Timpson, N. J., Smith, G. D., & Nordestgaard, B. G. (2011). 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. Journal of Internal Medicine, 269(5), 525-537. https://doi.org/10.1111/j.1365-2796.2011.02343.x

Vancouver

Lawlor DA, Harbord RM, Tybjaerg-Hansen A, Palmer TM, Zacho J, Benn M et al. 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. Journal of Internal Medicine. 2011 May;269(5):525-537. Epub 2011 Apr 17. doi: 10.1111/j.1365-2796.2011.02343.x

Author

Lawlor, Debbie A. ; Harbord, Roger M. ; Tybjaerg-Hansen, Anne et al. / 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. In: Journal of Internal Medicine. 2011 ; Vol. 269, No. 5. pp. 525-537.

Bibtex

@article{377ff556d99c42f1869ca7477e8f50c3,
title = "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",
abstract = "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.",
keywords = "Adiposity, Adult, Aged, Aged, 80 and over, Anxiety Disorders, Body Mass Index, Cohort Studies, Cross-Sectional Studies, Denmark, Female, Genetic Loci, Genotype, Humans, Male, Mendelian Randomization Analysis, Middle Aged, Proteins, Receptor, Melanocortin, Type 4, Risk Factors, Stress, Psychological, Waist-Hip Ratio, Young Adult",
author = "Lawlor, {Debbie A.} and Harbord, {Roger M.} and Anne Tybjaerg-Hansen and Palmer, {Tom M.} and Jeppe Zacho and Marianne Benn and Timpson, {Nicholas J.} and Smith, {George Davey} and Nordestgaard, {B{\o}rge G.}",
note = "{\textcopyright} 2011 The Association for the Publication of the Journal of Internal Medicine.",
year = "2011",
month = may,
doi = "10.1111/j.1365-2796.2011.02343.x",
language = "English",
volume = "269",
pages = "525--537",
journal = "Journal of Internal Medicine",
issn = "1365-2796",
publisher = "Wiley-Blackwell",
number = "5",

}

RIS

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 -