The genetics of bipolar disorder with obesity and type 2 diabetes.
Bipolar disorder
Diabetes type 2
Genome-wide association study
Genomics
Obesity
Polygenic risk score
Journal
Journal of affective disorders
ISSN: 1573-2517
Titre abrégé: J Affect Disord
Pays: Netherlands
ID NLM: 7906073
Informations de publication
Date de publication:
15 09 2022
15 09 2022
Historique:
received:
10
03
2022
accepted:
25
06
2022
pubmed:
6
7
2022
medline:
20
7
2022
entrez:
5
7
2022
Statut:
ppublish
Résumé
Bipolar disorder (BD) presents with high obesity and type 2 diabetes (T2D) and pathophysiological and phenomenological abnormalities shared with cardiometabolic disorders. Genomic studies may help define if they share genetic liability. This selective review of BD with obesity and T2D will focus on genomic studies, stress their current limitations and guide future steps in developing the field. We searched electronic databases (PubMed, Scopus) until December 2021 to identify genome-wide association studies, polygenic risk score analyses, and functional genomics of BD accounting for body mass index (BMI), obesity, or T2D. The first genome-wide association studies (GWAS) of BD accounting for obesity found a promising genome-wide association in an intronic gene variant of TCF7L2 that was further replicated. Polygenic risk scores of obesity and T2D have also been associated with BD, yet, no genetic correlations have been demonstrated. Finally, human-induced stem cell studies of the intronic variant in TCF7L2 show a potential biological impact of the products of this genetic variant in BD risk. The narrative nature of this review. Findings from BD GWAS accounting for obesity and their functional testing, have prompted potential biological insights. Yet, BD, obesity, and T2D display high phenotypic, genetic, and population-related heterogeneity, limiting our ability to detect genetic associations. Further studies should refine cardiometabolic phenotypes, test gene-environmental interactions and add population diversity.
Sections du résumé
BACKGROUND
Bipolar disorder (BD) presents with high obesity and type 2 diabetes (T2D) and pathophysiological and phenomenological abnormalities shared with cardiometabolic disorders. Genomic studies may help define if they share genetic liability. This selective review of BD with obesity and T2D will focus on genomic studies, stress their current limitations and guide future steps in developing the field.
METHODS
We searched electronic databases (PubMed, Scopus) until December 2021 to identify genome-wide association studies, polygenic risk score analyses, and functional genomics of BD accounting for body mass index (BMI), obesity, or T2D.
RESULTS
The first genome-wide association studies (GWAS) of BD accounting for obesity found a promising genome-wide association in an intronic gene variant of TCF7L2 that was further replicated. Polygenic risk scores of obesity and T2D have also been associated with BD, yet, no genetic correlations have been demonstrated. Finally, human-induced stem cell studies of the intronic variant in TCF7L2 show a potential biological impact of the products of this genetic variant in BD risk.
LIMITATIONS
The narrative nature of this review.
CONCLUSIONS
Findings from BD GWAS accounting for obesity and their functional testing, have prompted potential biological insights. Yet, BD, obesity, and T2D display high phenotypic, genetic, and population-related heterogeneity, limiting our ability to detect genetic associations. Further studies should refine cardiometabolic phenotypes, test gene-environmental interactions and add population diversity.
Identifiants
pubmed: 35780966
pii: S0165-0327(22)00744-3
doi: 10.1016/j.jad.2022.06.084
pmc: PMC9703971
mid: NIHMS1842372
pii:
doi:
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
222-231Subventions
Organisme : NCATS NIH HHS
ID : KL2 TR002379
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008685
Pays : United States
Organisme : NIMH NIH HHS
ID : K23 MH120503
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier B.V. All rights reserved.
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