Display options
Cite
Casanova F, O'Loughlin J, Martin S, et al. Higher adiposity and mental health: causal inference using Mendelian randomization. Hum Mol Genet. 2021;30(24):2371-2382doi: 10.1093/hmg/ddab204.
Casanova, F., O'Loughlin, J., Martin, S., Beaumont, R. N., Wood, A. R., Watkins, E. R., Freathy, R. M., Hagenaars, S. P., Frayling, T. M., Yaghootkar, H., & Tyrrell, J. (2021). Higher adiposity and mental health: causal inference using Mendelian randomization. Human molecular genetics, 30(24), 2371-2382. https://doi.org/10.1093/hmg/ddab204
Casanova, Francesco, et al. "Higher adiposity and mental health: causal inference using Mendelian randomization." Human molecular genetics vol. 30,24 (2021): 2371-2382. doi: https://doi.org/10.1093/hmg/ddab204
Casanova F, O'Loughlin J, Martin S, Beaumont RN, Wood AR, Watkins ER, Freathy RM, Hagenaars SP, Frayling TM, Yaghootkar H, Tyrrell J. Higher adiposity and mental health: causal inference using Mendelian randomization. Hum Mol Genet. 2021 Nov 30;30(24):2371-2382. doi: 10.1093/hmg/ddab204. PMID: 34270736; PMCID: PMC8643500.
Copy Download .nbib Format: NLM
Share it on

Hum Mol Genet. 2021 Nov 30;30(24):2371-2382. doi: 10.1093/hmg/ddab204.

Higher adiposity and mental health: causal inference using Mendelian randomization.

Human molecular genetics

Francesco Casanova, Jessica O'Loughlin, Susan Martin, Robin N Beaumont, Andrew R Wood, Edward R Watkins, Rachel M Freathy, Saskia P Hagenaars, Timothy M Frayling, Hanieh Yaghootkar, Jess Tyrrell

Affiliations

  1. Genetics of Complex Traits, The College of Medicine and Health, RD&E Hospital, University of Exeter, Exeter EX2 5DW, UK.
  2. Mood Disorders Centre, School of Psychology, University of Exeter, Exeter, EX4 4QG, UK.
  3. Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 8AF, UK.

PMID: 34270736 PMCID: PMC8643500 DOI: 10.1093/hmg/ddab204

Abstract

Higher adiposity is an established risk factor for psychiatric diseases including depression and anxiety. The associations between adiposity and depression may be explained by the metabolic consequences and/or by the psychosocial impact of higher adiposity. We performed one- and two- sample Mendelian randomization (MR) in up to 145 668 European participants from the UK Biobank to test for a causal effect of higher adiposity on 10 well-validated mental health and well-being outcomes derived using the Mental Health Questionnaire (MHQ). We used three sets of adiposity genetic instruments: (a) a set of 72 BMI genetic variants, (b) a set of 36 favourable adiposity variants and (c) a set of 38 unfavourable adiposity variants. We additionally tested causal relationships (1) in men and women separately, (2) in a subset of individuals not taking antidepressants and (3) in non-linear MR models. Two-sample MR provided evidence that a genetically determined one standard deviation (1-SD) higher BMI (4.6 kg/m2) was associated with higher odds of current depression [OR: 1.50, 95%CI: 1.15, 1.95] and lower well-being [ß: -0.15, 95%CI: -0.26, -0.04]. Findings were similar when using the metabolically favourable and unfavourable adiposity variants, with higher adiposity associated with higher odds of depression and lower well-being scores. Our study provides further evidence that higher BMI causes higher odds of depression and lowers well-being. Using genetics to separate out metabolic and psychosocial effects, our study suggests that in the absence of adverse metabolic effects higher adiposity remains causal to depression and lowers well-being.

© The Author(s) 2021. Published by Oxford University Press.

References

  1. Int J Obes (Lond). 2020 Feb;44(2):388-398 - PubMed
  2. Int J Epidemiol. 2020 Aug 1;49(4):1173-1184 - PubMed
  3. Transl Psychiatry. 2019 Aug 5;9(1):184 - PubMed
  4. Nat Genet. 2018 Jul;50(7):906-908 - PubMed
  5. Nat Genet. 2018 May;50(5):668-681 - PubMed
  6. Psychosom Med. 2007 Nov;69(8):740-7 - PubMed
  7. Int J Epidemiol. 2015 Apr;44(2):512-25 - PubMed
  8. BJPsych Open. 2020 Feb 06;6(2):e18 - PubMed
  9. Am Psychol. 2000 Jan;55(1):34-43 - PubMed
  10. Nature. 2018 Oct;562(7726):203-209 - PubMed
  11. Psychol Med. 2020 May;50(7):1129-1138 - PubMed
  12. Am J Epidemiol. 2003 Dec 15;158(12):1139-47 - PubMed
  13. J Psychosom Res. 2008 Jan;64(1):97-105 - PubMed
  14. Genet Epidemiol. 2016 May;40(4):304-14 - PubMed
  15. J Health Psychol. 2008 Nov;13(8):1190-7 - PubMed
  16. Arch Gen Psychiatry. 2010 Mar;67(3):220-9 - PubMed
  17. Int J Obes (Lond). 2012 Mar;36(3):414-21 - PubMed
  18. Am J Epidemiol. 2003 Jan 15;157(2):98-112 - PubMed
  19. Int J Obes (Lond). 2010 Mar;34(3):407-19 - PubMed
  20. Int J Epidemiol. 2019 Jun 1;48(3):834-848 - PubMed
  21. BMJ. 2018 Sep 25;362:k3788 - PubMed
  22. J Epidemiol Community Health. 2018 Aug;72(8):708-710 - PubMed
  23. Am J Epidemiol. 2011 Feb 15;173(4):421-9 - PubMed
  24. Sci Rep. 2016 Sep 07;6:32730 - PubMed
  25. Nat Commun. 2020 Jul 14;11(1):3519 - PubMed
  26. Nat Commun. 2021 Feb 9;12(1):886 - PubMed
  27. Nat Rev Immunol. 2016 Jan;16(1):22-34 - PubMed
  28. Ann Epidemiol. 2008 Jun;18(6):458-66 - PubMed
  29. Genet Epidemiol. 2017 May;41(4):341-352 - PubMed
  30. PLoS Med. 2015 Mar 31;12(3):e1001779 - PubMed
  31. BMJ. 2003 Dec 13;327(7428):1383-4 - PubMed
  32. Br J Psychiatry. 2014 Jul;205(1):24-8 - PubMed
  33. BMJ. 2016 Mar 08;352:i582 - PubMed
  34. Clin Pract Epidemiol Ment Health. 2016 Oct 31;12:67-74 - PubMed
  35. JAMA Psychiatry. 2021 Feb 1;78(2):161-170 - PubMed
  36. Int J Obes (Lond). 2008 Mar;32(3):558-66 - PubMed
  37. Hum Mol Genet. 2018 Aug 1;27(R2):R195-R208 - PubMed
  38. Nature. 2015 Feb 12;518(7538):197-206 - PubMed

Publication Types

Grant support