Major depressive disorder and current psychological distress moderate the effect of polygenic risk for obesity on body mass index

T-K Clarke, L S Hall, A M Fernandez-Pujals, D J MacIntyre, P Thomson, C Hayward, B H Smith, S Padmanabhan, L J Hocking, I J Deary, D J Porteous, A M McIntosh

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Abstract

Major depressive disorder (MDD) and obesity are frequently co-morbid and this correlation is partly due to genetic factors. Although specific genetic risk variants are associated with body mass index (BMI) and with larger effect sizes in depressed individuals, the genetic overlap and interaction with depression has not been addressed using whole-genome data. Polygenic profile scores for MDD and BMI were created in 13,921 members of Generation Scotland: the Scottish Family Health Study and tested for their association with BMI, MDD, neuroticism and scores on the General Health Questionnaire (GHQ) (current psychological distress). The association between BMI polygenic profile scores and BMI was tested fitting GHQ, neuroticism or MDD status as an interaction term to test for a moderating effect of mood disorder. BMI polygenic profile scores were not associated with lifetime MDD status or neuroticism although a significant positive association with GHQ scores was found (P = 0.0001, β = 0.034, r(2) = 0.001). Polygenic risk for MDD was not associated with BMI. A significant interaction between BMI polygenic profile scores and MDD (P = 0.0003, β = 0.064), GHQ (P = 0.0005, β = 0.027) and neuroticism (P = 0.003, β = 0.023) was found when BMI was the dependent variable. The effect of BMI-increasing alleles was greater in those with MDD, high neuroticism or current psychological distress. MDD, neuroticism and current psychological distress amplify the effect of BMI polygenic profile scores on BMI. Depressed individuals with a greater polygenic load for obesity are at greater risk of becoming obese than control individuals.

Original languageEnglish
Pages (from-to)e592
JournalTranslational Psychiatry
Volume5
DOIs
Publication statusPublished - 30 Jun 2015

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Major Depressive Disorder
Body Mass Index
Obesity
Psychology
Health
Family Health
Scotland
Mood Disorders
Neuroticism
Alleles
Genome
Depression

Keywords

  • Adult
  • Anxiety Disorders
  • Body Mass Index
  • Comorbidity
  • Depressive Disorder, Major
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Multifactorial Inheritance
  • Obesity
  • Risk Factors
  • Stress, Psychological
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Clarke, T-K., Hall, L. S., Fernandez-Pujals, A. M., MacIntyre, D. J., Thomson, P., Hayward, C., ... McIntosh, A. M. (2015). Major depressive disorder and current psychological distress moderate the effect of polygenic risk for obesity on body mass index. Translational Psychiatry, 5, e592. https://doi.org/10.1038/tp.2015.83

Major depressive disorder and current psychological distress moderate the effect of polygenic risk for obesity on body mass index. / Clarke, T-K; Hall, L S; Fernandez-Pujals, A M; MacIntyre, D J; Thomson, P; Hayward, C; Smith, B H; Padmanabhan, S; Hocking, L J; Deary, I J; Porteous, D J; McIntosh, A M.

In: Translational Psychiatry, Vol. 5, 30.06.2015, p. e592.

Research output: Contribution to journalArticle

Clarke, T-K, Hall, LS, Fernandez-Pujals, AM, MacIntyre, DJ, Thomson, P, Hayward, C, Smith, BH, Padmanabhan, S, Hocking, LJ, Deary, IJ, Porteous, DJ & McIntosh, AM 2015, 'Major depressive disorder and current psychological distress moderate the effect of polygenic risk for obesity on body mass index', Translational Psychiatry, vol. 5, pp. e592. https://doi.org/10.1038/tp.2015.83
Clarke, T-K ; Hall, L S ; Fernandez-Pujals, A M ; MacIntyre, D J ; Thomson, P ; Hayward, C ; Smith, B H ; Padmanabhan, S ; Hocking, L J ; Deary, I J ; Porteous, D J ; McIntosh, A M. / Major depressive disorder and current psychological distress moderate the effect of polygenic risk for obesity on body mass index. In: Translational Psychiatry. 2015 ; Vol. 5. pp. e592.
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abstract = "Major depressive disorder (MDD) and obesity are frequently co-morbid and this correlation is partly due to genetic factors. Although specific genetic risk variants are associated with body mass index (BMI) and with larger effect sizes in depressed individuals, the genetic overlap and interaction with depression has not been addressed using whole-genome data. Polygenic profile scores for MDD and BMI were created in 13,921 members of Generation Scotland: the Scottish Family Health Study and tested for their association with BMI, MDD, neuroticism and scores on the General Health Questionnaire (GHQ) (current psychological distress). The association between BMI polygenic profile scores and BMI was tested fitting GHQ, neuroticism or MDD status as an interaction term to test for a moderating effect of mood disorder. BMI polygenic profile scores were not associated with lifetime MDD status or neuroticism although a significant positive association with GHQ scores was found (P = 0.0001, β = 0.034, r(2) = 0.001). Polygenic risk for MDD was not associated with BMI. A significant interaction between BMI polygenic profile scores and MDD (P = 0.0003, β = 0.064), GHQ (P = 0.0005, β = 0.027) and neuroticism (P = 0.003, β = 0.023) was found when BMI was the dependent variable. The effect of BMI-increasing alleles was greater in those with MDD, high neuroticism or current psychological distress. MDD, neuroticism and current psychological distress amplify the effect of BMI polygenic profile scores on BMI. Depressed individuals with a greater polygenic load for obesity are at greater risk of becoming obese than control individuals.",
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AU - Hall, L S

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AB - Major depressive disorder (MDD) and obesity are frequently co-morbid and this correlation is partly due to genetic factors. Although specific genetic risk variants are associated with body mass index (BMI) and with larger effect sizes in depressed individuals, the genetic overlap and interaction with depression has not been addressed using whole-genome data. Polygenic profile scores for MDD and BMI were created in 13,921 members of Generation Scotland: the Scottish Family Health Study and tested for their association with BMI, MDD, neuroticism and scores on the General Health Questionnaire (GHQ) (current psychological distress). The association between BMI polygenic profile scores and BMI was tested fitting GHQ, neuroticism or MDD status as an interaction term to test for a moderating effect of mood disorder. BMI polygenic profile scores were not associated with lifetime MDD status or neuroticism although a significant positive association with GHQ scores was found (P = 0.0001, β = 0.034, r(2) = 0.001). Polygenic risk for MDD was not associated with BMI. A significant interaction between BMI polygenic profile scores and MDD (P = 0.0003, β = 0.064), GHQ (P = 0.0005, β = 0.027) and neuroticism (P = 0.003, β = 0.023) was found when BMI was the dependent variable. The effect of BMI-increasing alleles was greater in those with MDD, high neuroticism or current psychological distress. MDD, neuroticism and current psychological distress amplify the effect of BMI polygenic profile scores on BMI. Depressed individuals with a greater polygenic load for obesity are at greater risk of becoming obese than control individuals.

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KW - Anxiety Disorders

KW - Body Mass Index

KW - Comorbidity

KW - Depressive Disorder, Major

KW - Female

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Humans

KW - Male

KW - Middle Aged

KW - Multifactorial Inheritance

KW - Obesity

KW - Risk Factors

KW - Stress, Psychological

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

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