The genetics of bipolar disorder with obesity and type 2 diabetes

Alessandro Miola, Eleanna De Filippis, Marin Veldic, Ada Man Choi Ho, Stacey J. Winham, Mariana Mendoza, Francisco Romo-Nava, Nicolas A. Nunez, Manuel Gardea Resendez, Miguel L. Prieto, Susan L. McElroy, Joanna M. Biernacka, Mark A. Frye, Alfredo B. Cuellar-Barboza*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)222-231
Number of pages10
JournalJournal of Affective Disorders
Volume313
DOIs
StatePublished - 15 Sep 2022

Bibliographical note

Funding Information:
NA Nuñez is supported by a grant from the National Institute of General Medical Sciences of the National Institutes of Health under award number T32 GM008685.Francisco Romo-Nava MD, PhD, receives grant support from the National Institute of Mental Health K23 Award (K23MH120503) and from a 2017 NARSAD Young Investigator Award from the Brain and Behavior Research Foundation; has a U.S. Patent and Trademark Office patent # 10,857,356; and has received non-financial research support from Soterix Medical.Mark Frye M.D. Grant Support; Assurex Health, Mayo Foundation and Intellectual property licensed to Chymia LLC. with rights to receive future royalties.

Funding Information:
NA Nuñez is supported by a grant from the National Institute of General Medical Sciences of the National Institutes of Health under award number T32 GM008685 .

Funding Information:
Francisco Romo-Nava MD, PhD, receives grant support from the National Institute of Mental Health K23 Award ( K23MH120503 ) and from a 2017 NARSAD Young Investigator Award from the Brain and Behavior Research Foundation ; has a U.S. Patent and Trademark Office patent # 10,857,356; and has received non-financial research support from Soterix Medical.

Publisher Copyright:
© 2022 Elsevier B.V.

Keywords

  • Bipolar disorder
  • Diabetes type 2
  • Genome-wide association study
  • Genomics
  • Obesity
  • Polygenic risk score

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