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Investigating the association between body fat and depression via Mendelian randomization.

ABSTRACT: Obesity and depression are major public health concerns that are both associated with substantial morbidity and mortality. There is a considerable body of literature linking obesity to the development of depression. Recent studies using Mendelian randomization indicate that this relationship is causal. Most studies of the obesity-depression association have used body mass index as a measure of obesity. Body mass index is defined as weight (measured in kilograms) divided by the square of height (meters) and therefore does not distinguish between the contributions of fat and nonfat to body weight. To better understand the obesity-depression association, we conduct a Mendelian randomization study of the relationship between fat mass, nonfat mass, height, and depression, using genome-wide association study results from the UK Biobank (n?=?332,000) and the Psychiatric Genomics Consortium (n?=?480,000). Our findings suggest that both fat mass and height (short stature) are causal risk factors for depression, while nonfat mass is not. These results represent important new knowledge on the role of anthropometric measures in the etiology of depression. They also suggest that reducing fat mass will decrease the risk of depression, which lends further support to public health measures aimed at reducing the obesity epidemic.

SUBMITTER: Speed MS

PROVIDER: S-EPMC6683191 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Investigating the association between body fat and depression via Mendelian randomization.

Speed Maria S MS Jefsen Oskar H OH Børglum Anders D AD Speed Doug D Østergaard Søren D SD

Translational psychiatry 20190805 1

Obesity and depression are major public health concerns that are both associated with substantial morbidity and mortality. There is a considerable body of literature linking obesity to the development of depression. Recent studies using Mendelian randomization indicate that this relationship is causal. Most studies of the obesity-depression association have used body mass index as a measure of obesity. Body mass index is defined as weight (measured in kilograms) divided by the square of height ( ...[more]

PMID: 31383844

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Project description:BackgroundInsulin resistance (IR) with associated compensatory hyperinsulinemia (HI) are early abnormalities in the etiology of prediabetes (preT2D) and type 2 diabetes (T2D). IR and HI also associate with increased erythrocytosis. Hemoglobin A1c (HbA1c) is commonly used to diagnose and monitor preT2D and T2D, but can be influenced by erythrocytosis independent of glycemia.MethodsWe undertook bidirectional Mendelian randomization (MR) in individuals of European ancestry to investigate potential causal associations between increased fasting insulin adjusted for BMI (FI), erythrocytosis and its non-glycemic impact on HbA1c. We investigated the association between the triglyceride-glucose index (TGI), a surrogate measure of IR and HI, and glycation gap (difference between measured HbA1c and predicted HbA1c derived from linear regression of fasting glucose) in people with normoglycemia and preT2D.ResultsInverse variance weighted MR (IVWMR) suggested that increased FI increases hemoglobin (Hb, b=0.54 ± 0.09, p=2.7 x 10-10), red cell count (RCC, b=0.54 ± 0.12, p=5.38x10-6) and reticulocyte (RETIC, b=0.70 ± 0.15, p=2.18x10-6). Multivariable MR indicated that increased FI did not impact HbA1c (b=0.23 ± 0.16, p=0.162) but reduced HbA1c after adjustment for T2D (b=0.31 ± 0.13, p=0.016). Increased Hb (b=0.03 ± 0.01, p=0.02), RCC (b=0.02 ± 0.01, p=0.04) and RETIC (b=0.03 ± 0.01, p=0.002) might modestly increase FI. In the observational cohort, increased TGI associated with decreased glycation gap, (i.e., measured HbA1c was lower than expected based on fasting glucose, (b=-0.09 ± 0.009, p<0.0001)) in people with preT2D but not in those with normoglycemia (b=0.02 ± 0.007, p<0.0001).ConclusionsMR suggests increased FI increases erythrocytosis and might potentially decrease HbA1c by non-glycemic effects. Increased TGI, a surrogate measure of increased FI, associates with lower-than-expected HbA1c in people with preT2D. These findings merit confirmatory studies to evaluate their clinical significance.

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Investigating the association between body fat and depression via Mendelian randomization.

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Investigating the association between body fat and depression via Mendelian randomization.

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