Shared genetics between classes of obesity and psychiatric disorders: A large-scale genome-wide cross-trait analysis

Ding, Hui; Ouyang, Mengyuan; Wang, Jinyi; Xie, Minyao; Huang, Yanyuan; Yuan, Fangzheng; Jia, Yunhan; Zhang, Xuedi; Liu, Na; Zhang, Ning

doi:10.1016/j.jpsychores.2022.111032

Cited by 8 publications

(11 citation statements)

References 79 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%

“…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) 25,31,32,35,37–40,43–49,51–61,64–70 , but an F-statistic ≥10 (n=27 studies) 25,32–36,38,44,47–49,51,53,55–60,62–65,67,68,70 , 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: Resultsmentioning

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%

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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“…Viele psychiatrische Erkrankungen gehen mit einem subjektiven Gefühl der Kraft- und Energielosigkeit einher, was sich auch objektiv in einer geringeren körperlichen und kognitiven Leistungsfähigkeit abbildet. Zudem besteht ein bidirektionaler Zusammenhang zwischen Adipositas und psychischer Gesundheit, welcher nur unzureichend durch Psychopharmakotherapie und einen ungesunden Lebensstil erklärt werden kann [ 31 ]. Umgekehrt konnte gezeigt werden, dass eine FMT von Patientinnen mit Anorexia nervosa zu einer verminderten Gewichtszunahme bei GF-Mäusen führt [ 32 ].…”

Section: Mikrobiota-hirn-achse: Kommunikationswege Im Zusammenhang Mi...unclassified

The importance of the human microbiome for mental health

Refisch,

Walter

2023

Nervenarzt

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ZusammenfassungDie Zusammensetzung des Mikrobioms ist bei vielen häufigen psychiatrischen Erkrankungen verändert. Präklinische Studien haben wichtige Mechanismen aufgedeckt, über die das Mikrobiom mit neuronalen Funktionen im bidirektionalen Austausch steht. Dysregulationen im komplexen Zusammenspiel von Mikrobiom, Immunsystem, Stress-Response und Energiehomöostase könnten insbesondere in der frühen Lebensphase für die Entwicklung psychiatrischer Symptome im späteren Leben prädisponieren. Obwohl bisher nur wenige klinische Studien vorliegen, haben der weitreichende Einfluss des Mikrobioms auf neuronale und psychische Funktionen sowie seine hohe Plastizität großes Interesse an seinem therapeutischen Potenzial bei häufigen psychiatrischen Störungen geweckt.

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“…Among the five IgLON family members, both NEGR1 and OPCML have been linked to major depressive disorder [ 16 , 17 , 18 , 19 , 20 ], schizophrenia [ 21 , 22 , 23 , 24 , 25 , 26 ], autism [ 27 , 28 ], anorexia nervosa [ 29 , 30 ], and Alzheimer’s disease [ 31 , 32 ]. Other pathologies and disorders ranging from dyslexia to Huntington’s disease and obesity were attributed to alterations in one gene or the other [ 33 ].…”

Section: Introductionmentioning

confidence: 99%

The Risk Genes for Neuropsychiatric Disorders negr1 and opcml Are Expressed throughout Zebrafish Brain Development

Habicher,

Sanvido,

Bühler

et al. 2024

Genes

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The immunoglobulin LAMP/OBCAM/NTM (IgLON) family of cell adhesion molecules comprises five members known for their involvement in establishing neural circuit connectivity, fine-tuning, and maintenance. Mutations in IgLON genes result in alterations in these processes and can lead to neuropsychiatric disorders. The two IgLON family members NEGR1 and OPCML share common links with several of them, such as schizophrenia, autism, and major depressive disorder. However, the onset and the underlying molecular mechanisms have remained largely unresolved, hampering progress in developing therapies. NEGR1 and OPCML are evolutionarily conserved in teleosts like the zebrafish (Danio rerio), which is excellently suited for disease modelling and large-scale screening for disease-ameliorating compounds. To explore the potential applicability of zebrafish for extending our knowledge on NEGR1- and OPCML-linked disorders and to develop new therapeutic strategies, we investigated the spatio-temporal expression of the two genes during early stages of development. negr1 and opcml are expressed maternally and subsequently in partially distinct domains of conserved brain regions. Other areas of expression in zebrafish have not been reported in mammals to date. Our results indicate that NEGR1 and OPCML may play roles in neural circuit development and function at stages earlier than previously anticipated. A detailed functional analysis of the two genes based on our findings could contribute to understanding the mechanistic basis of related psychiatric disorders.

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Shared genetics between classes of obesity and psychiatric disorders: A large-scale genome-wide cross-trait analysis

Cited by 8 publications

References 79 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

The importance of the human microbiome for mental health

The Risk Genes for Neuropsychiatric Disorders negr1 and opcml Are Expressed throughout Zebrafish Brain Development

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