Dataset Information

Obesity and atypical depression symptoms: findings from Mendelian randomization in two European cohorts.

ABSTRACT: Studies considering the causal role of body mass index (BMI) for the predisposition of major depressive disorder (MDD) based on a Mendelian Randomization (MR) approach have shown contradictory results. These inconsistent findings may be attributable to the heterogeneity of MDD; in fact, several studies have documented associations between BMI and mainly the atypical subtype of MDD. Using a MR approach, we investigated the potential causal role of obesity in both the atypical subtype and its five specific symptoms assessed according to the Statistical Manual of Mental Disorders (DSM), in two large European cohorts, CoLaus|PsyCoLaus (n?=?3350, 1461 cases and 1889 controls) and NESDA|NTR (n?=?4139, 1182 cases and 2957 controls). We first tested general obesity measured by BMI and then the body fat distribution measured by waist-to-hip ratio (WHR). Results suggested that BMI is potentially causally related to the symptom increase in appetite, for which inverse variance weighted, simple median and weighted median MR regression estimated slopes were 0.68 (SE?=?0.23, p?=?0.004), 0.77 (SE?=?0.37, p?=?0.036), and 1.11 (SE?=?0.39, p?=?0.004). No causal effect of BMI or WHR was found on the risk of the atypical subtype or for any of the other atypical symptoms. Our findings show that higher obesity is likely causal for the specific symptom of increase in appetite in depressed participants and reiterate the need to study depression at the granular level of its symptoms to further elucidate potential causal relationships and gain additional insight into its biological underpinnings.

SUBMITTER: Pistis G

PROVIDER: S-EPMC7862438 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Obesity and atypical depression symptoms: findings from Mendelian randomization in two European cohorts.

Pistis Giorgio G Milaneschi Yuri Y Vandeleur Caroline L CL Lasserre Aurélie M AM Penninx Brenda W J H BWJH Lamers Femke F Boomsma Dorret I DI Hottenga Jouke-Jan JJ Marques-Vidal Pedro P Vollenweider Peter P Waeber Gérard G Aubry Jean-Michel JM Preisig Martin M Kutalik Zoltán Z

Translational psychiatry 20210204 1

Studies considering the causal role of body mass index (BMI) for the predisposition of major depressive disorder (MDD) based on a Mendelian Randomization (MR) approach have shown contradictory results. These inconsistent findings may be attributable to the heterogeneity of MDD; in fact, several studies have documented associations between BMI and mainly the atypical subtype of MDD. Using a MR approach, we investigated the potential causal role of obesity in both the atypical subtype and its five ...[more]

PMID: 33542229

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Project description:BackgroundObesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH)D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis.Methods and findingsWe used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH)D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n?=?123,864). Each 1 kg/m(2) higher BMI was associated with 1.15% lower 25(OH)D (p?=?6.52×10?²?). The BMI allele score was associated both with BMI (p?=?6.30×10??²) and 25(OH)D (-0.06% [95% CI -0.10 to -0.02], p?=?0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH)D (p?8.07×10??? for both scores) but not with BMI (synthesis score, p?=?0.88; metabolism score, p?=?0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH)D concentrations (IV ratio: -4.2 [95% CI -7.1 to -1.3], p?=?0.005). No association was seen for genetically instrumented 25(OH)D with BMI, a finding that was confirmed using data from the GIANT consortium (p?0.57 for both vitamin D scores).ConclusionsOn the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH)D, while any effects of lower 25(OH)D increasing BMI are likely to be small. Population level interventions to reduce BMI are expected to decrease the prevalence of vitamin D deficiency.

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Dataset Information

Obesity and atypical depression symptoms: findings from Mendelian randomization in two European cohorts.

Publications

Obesity and atypical depression symptoms: findings from Mendelian randomization in two European cohorts.

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