Assessing the Evidence for Causal Associations Between Body Mass Index, C-Reactive Protein, Depression, and Reported Trauma Using Mendelian Randomization

Palmos, Alish; Hübel, Christopher; Lim, Kai Xiang; Hunjan, Avina; Coleman, Jonathan; Breen, Gerome

doi:10.1016/j.bpsgos.2022.01.003

Cited by 6 publications

(9 citation statements)

References 81 publications

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“…Study characteristics and reported associations of the included studies are given in Table 1 , and additional details are presented in Appendix . Twenty-eight studies reported 98 estimates of the association between adiposity and depression 25,32–35,37,40,42–45,47,48,50,53,55–59,62–64,66–70 , three studies reported 9 estimates for anxiety 25,41,67 , three studies reported 8 estimates for anorexia nervosa 61,67,68 , five studies reported 13 estimates for bipolar disorder 31,53,55,65,67 , three studies reported 7 estimates for OCD 61,67,68 , three studies reported 23 estimates for PTSD 49,60,67 , and twelve studies reported 26 estimates for schizophrenia 36,38,39,46,51,52,54,55,61,65,67,68 . One-sample MR design was conducted in six studies 33,34,43,56,57,62 , two-sample MR design was conducted in thirty-two studies 31,32,35–42,44–55,58,60,61,63–69 , both one-sample MR and two-sample MR were conducted in three studies 25,59,70 .…”

Section: Resultsmentioning

confidence: 99%

“…The search strategy resulted in 1,935 articles, of which 41 eligible Mendelian randomization studies with 184 estimates were included in this review (Figure 1, Supplementary material 1 and Supplementary material 2). Among them, nineteen studies reported 1 estimate [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49] , five studies reported 2 estimates [50][51][52][53][54] , two studies reported 3 estimates 55,56 , three studies reported 4 estimates [57][58][59] , and twelve studies reported 5+ estimates 25,[60][61][62][63][64][65][66][67][68][69][70] . Study characteristics and reported associations of the included studies are given in Table 1, and additional details are presented in Appendix.…”

Section: Resultsmentioning

confidence: 99%

“…Twenty-eight studies reported 98 estimates of the association between adiposity and depression 25,[32][33][34][35]37,40,[42][43][44][45]47,48,50,53,[55][56][57][58][59][62][63][64][66][67][68][69][70] , three studies reported 9 estimates for anxiety 25,41,67 , three studies reported 8 estimates for anorexia nervosa 61,67,68 , five studies reported 13 estimates for bipolar disorder 31,53,55,65,67 , three studies reported 7 estimates for OCD 61,67,68 , three studies reported 23 estimates for PTSD 49,60,67 , and twelve studies reported 26 estimates for schizophrenia 36,38,39,46,51,…”

Section: Resultsmentioning

confidence: 99%

“…For the assessment of exposure and outcome, 86% of studies used adiposity data from the UK Biobank and mental illness data from Psychiatric Genomics Consortium. For the selection of genetic variants, most studies selected a genetic variant p-value threshold below 5E-08 (n=32 studies) , but an F-statistic ≥10 (n=27 studies) 25,[32][33][34][35][36]38,44,[47][48][49]51,53,[55][56][57][58][59][60][62][63][64][65]67,68,70 , and had a high percentage (≥3%) of explained variance (n=11 studies) 32,35,38,51,55,58,60,62,64,66 , providing good evidence that the chosen instrument was robust.…”

Section: Quality Assessment Of Included Studiesmentioning

confidence: 99%

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The causal role of adiposity in mental illness: A systematic review and meta-analysis of Mendelian randomization studies

Gao,

Doody,

Koutoukidis

et al. 2024

Preprint

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Importance: Excess adiposity is associated with mental illnesses, but the causality of these associations remains equivocal. Objective: To examine the causal effect of adiposity on mental illnesses by summarizing and assessing evidence from Mendelian randomization (MR) studies. Study Selection: Searches were conducted on Embase, Medline, and Web of Science from database inception to January 8th 2024. Data Extraction and Synthesis: Studies using MR study designs that estimated adiposity measures including body mass index, abdominal adiposity, peripheral adiposity, or body composition in relation to mental illnesses were included. Study quality was assessed with a scoring system reflecting MR study guidelines. Data were pooled in meta-analyses using random-effects models. Subgroup analyses were conducted by sex. Main Outcomes and Measures: Outcomes were the presence or severity of depression, anxiety, eating disorders, bipolar disorder, obsessive compulsive disorder, post-traumatic stress disorder, schizophrenia, and related psychotic disorders. Results: Forty-one studies with 184 MR estimates were included in the systematic review; and 16 studies with 30 MR estimates were included in meta-analysis. Pooled estimates suggested that general adiposity was causally associated with depression (OR: 1.05, 95% CI, 1.00-1.10, p<0.001; I2=82.8%), though the effect size was modest and there was high heterogeneity. Subgroup difference by sex in the causal relationship was not observed (p=0.382). No evidence of causal associations was found between adiposity and other mental illnesses, though these analyses were characterized by high imprecision and heterogeneity. Conclusion and Relevance: General adiposity appears to be causally associated with depression, suggesting psychological benefits of weight management. Evidence for causal associations between adiposity and other mental illnesses remains uncertain.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Quality Assessment Of Included Studiesmentioning

confidence: 99%

See 2 more Smart Citations

The causal role of adiposity in mental illness: A systematic review and meta-analysis of Mendelian randomization studies

Gao,

Doody,

Koutoukidis

et al. 2024

Preprint

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“…Recently, a genome-wide association study (GWAS) reported that SNPs were associated with trauma, making it possible to explore the causal relationship between trauma and psychiatric disorders ( 15 ). Using MR method, trauma exposure was demonstrated to increase the risk of major depressive disorder ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

Assessing the causal association of trauma with subsequent psychiatric disorders by a Mendelian randomization study trauma and common psychiatric disorders

Liu

2023

Front. Psychiatry

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ObjectiveTrauma has been proposed as a risk factor for the development of psychiatric disorders. This study aimed to determine the causal role of trauma in six common psychiatric disorders.MethodsWe obtained summary-level data for genetic variants associated with trauma and the corresponding association with psychiatric disorders from previous genome-wide association studies. Two-sample Mendelian randomization analyzes were performed to estimate the causal association between trauma and psychiatric disorders, with inverse variance weighted used as the main method.ResultsGenetically predisposed trauma was associated with an increased risk of psychiatric disorders [odds ratio (OR) =1.24, 95%, confidence interval (CI), 1.09–1.40], anxiety disorder (OR = 1.30, 95% CI, 1.10–1.52) and schizophrenia (OR = 1.48, 95% CI, 1.18–1.84). However, the associations between trauma and sleep disorder (OR = 1.17, 95% CI, 1.01–1.35), as well as depression (OR = 1.09, 95% CI, 1.02–1.16) did not reach a Bonferroni corrected significance level. Besides, no association was observed between trauma and risk of bipolar disorder (OR = 1.21, 95% CI, 0.98–1.48) and eating disorder (OR = 1.28, 95% CI, 0.88–1.86).ConclusionTrauma might be causally associated with an increased risk of some common psychiatric disorders such as anxiety disorder and schizophrenia. However, little evidence supported an association between trauma and risk of depression, bipolar disorder, sleep disorder, and eating disorder. Our findings offered novel insights into the trauma-mediated development mechanism of psychiatric disorders, and psychological intervention to patients with trauma may be an effective prevention strategy for psychological diseases.

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The role of inflammatory biomarkers in the association between rheumatoid arthritis and depression: a Mendelian randomization study

Xiang

Jin

et al. 2023

Inflammopharmacol

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Assessing the Evidence for Causal Associations Between Body Mass Index, C-Reactive Protein, Depression, and Reported Trauma Using Mendelian Randomization

Cited by 6 publications

References 81 publications

The causal role of adiposity in mental illness: A systematic review and meta-analysis of Mendelian randomization studies

The causal role of adiposity in mental illness: A systematic review and meta-analysis of Mendelian randomization studies

Assessing the causal association of trauma with subsequent psychiatric disorders by a Mendelian randomization study trauma and common psychiatric disorders

The role of inflammatory biomarkers in the association between rheumatoid arthritis and depression: a Mendelian randomization study

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