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

Clarke TK, Hall LS, Fernandez-Pujals AM, MacIntyre DJ, Thomson P, Hayward C, Smith BH, Padmanabhan S, Hocking LJ, Deary IJ, Porteous DJ, McIntosh AM - Transl Psychiatry (2015)

Bottom Line: 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.The effect of BMI-increasing alleles was greater in those with MDD, high neuroticism or current psychological distress.Depressed individuals with a greater polygenic load for obesity are at greater risk of becoming obese than control individuals.

View Article: PubMed Central - PubMed

Affiliation: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.

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.

No MeSH data available.


Related in: MedlinePlus

Proportion of variance in BMI explained by BMI polygenic profile scores at five different thresholds in GS:SFHS (14 k). DEP=2030 MDD cases, CONS=11 836 controls, TOTAL=13 921 of total sample. All associations significant at P⩽3.2 × 10−19. BMI, body mass index; DEP, major depressive disorder; GS:SFHS, Generation Scotland: the Scottish Family Health Study; PGRS, polygenic risk score.
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fig2: Proportion of variance in BMI explained by BMI polygenic profile scores at five different thresholds in GS:SFHS (14 k). DEP=2030 MDD cases, CONS=11 836 controls, TOTAL=13 921 of total sample. All associations significant at P⩽3.2 × 10−19. BMI, body mass index; DEP, major depressive disorder; GS:SFHS, Generation Scotland: the Scottish Family Health Study; PGRS, polygenic risk score.

Mentions: A significant interaction between BMI polygenic profile scores and MDD status was found at the P-value threshold ⩽0.1 in relation to BMI (β=0.064, P=0.0032) (Table 3). Figure 1 illustrates the relationship between BMI polygenic profile scores and BMI in MDD cases and controls. The effect of BMI polygenic profile scores on BMI is greater in individuals with MDD (MDD cases β=0.265 vs controls β=0.188). Figure 2 shows the amount of variance explained by BMI polygenic profile scores in MDD cases, controls and the total sample. At a P-value threshold of P ⩽0.1, BMI polygenic profile scores explain 6.5% of the variance in BMI among MDD cases in comparison with 3.7% of the variance in controls. The interaction term was not significant at the P-value thresholds other than P ⩽0.1, but the direction of effect was consistent across all five scores.


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

Clarke TK, Hall LS, Fernandez-Pujals AM, MacIntyre DJ, Thomson P, Hayward C, Smith BH, Padmanabhan S, Hocking LJ, Deary IJ, Porteous DJ, McIntosh AM - Transl Psychiatry (2015)

Proportion of variance in BMI explained by BMI polygenic profile scores at five different thresholds in GS:SFHS (14 k). DEP=2030 MDD cases, CONS=11 836 controls, TOTAL=13 921 of total sample. All associations significant at P⩽3.2 × 10−19. BMI, body mass index; DEP, major depressive disorder; GS:SFHS, Generation Scotland: the Scottish Family Health Study; PGRS, polygenic risk score.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4490293&req=5

fig2: Proportion of variance in BMI explained by BMI polygenic profile scores at five different thresholds in GS:SFHS (14 k). DEP=2030 MDD cases, CONS=11 836 controls, TOTAL=13 921 of total sample. All associations significant at P⩽3.2 × 10−19. BMI, body mass index; DEP, major depressive disorder; GS:SFHS, Generation Scotland: the Scottish Family Health Study; PGRS, polygenic risk score.
Mentions: A significant interaction between BMI polygenic profile scores and MDD status was found at the P-value threshold ⩽0.1 in relation to BMI (β=0.064, P=0.0032) (Table 3). Figure 1 illustrates the relationship between BMI polygenic profile scores and BMI in MDD cases and controls. The effect of BMI polygenic profile scores on BMI is greater in individuals with MDD (MDD cases β=0.265 vs controls β=0.188). Figure 2 shows the amount of variance explained by BMI polygenic profile scores in MDD cases, controls and the total sample. At a P-value threshold of P ⩽0.1, BMI polygenic profile scores explain 6.5% of the variance in BMI among MDD cases in comparison with 3.7% of the variance in controls. The interaction term was not significant at the P-value thresholds other than P ⩽0.1, but the direction of effect was consistent across all five scores.

Bottom Line: 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.The effect of BMI-increasing alleles was greater in those with MDD, high neuroticism or current psychological distress.Depressed individuals with a greater polygenic load for obesity are at greater risk of becoming obese than control individuals.

View Article: PubMed Central - PubMed

Affiliation: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.

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.

No MeSH data available.


Related in: MedlinePlus