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Effects of ANK3 variation on gray and white matter in bipolar disorder

Molecular Psychiatry volume 22, pages 1345–1351 (2017)Cite this article

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Abstract

The single-nucleotide polymorphism rs9804190 in the Ankyrin G (ANK3) gene has been reported in genome-wide association studies to be associated with bipolar disorder (BD). However, the neural system effects of rs9804190 in BD are not known. We investigated associations between rs9804190 and gray and white matter (GM and WM, respectively) structure within a frontotemporal neural system implicated in BD. A total of 187 adolescent and adult European Americans were studied: a group homozygous for the C allele (52 individuals with BD and 56 controls) and a T-carrier group, carrying the high-risk T allele (38 BD and 41 controls). Subjects participated in high-resolution structural magnetic resonance imaging and diffusion tensor imaging (DTI) scanning. Frontotemporal region of interest (ROI) and whole-brain exploratory analyses were conducted. DTI ROI-based analysis revealed a significant diagnosis by genotype interaction within the uncinate fasciculus (P⩽0.05), with BD subjects carrying the T (risk) allele showing decreased fractional anisotropy compared with other subgroups, independent of age. Genotype effects were not observed in frontotemporal GM volume. These findings support effects of rs9804190 on frontotemporal WM in adolescents and adults with BD and suggest a mechanism contributing to WM pathology in BD.

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Acknowledgements

We were supported by research grants from the National Institute of Health (NIH) R01MH69747(HPB), R01MH070902(HPB), R01DA12690(JG), R01DA12849(JG), RC1MH088366(HPB), T32MH014276(ETCL), T32DA022975(ETCL) and K01MH086621(FW); CTSA UL1TR000142 from the NIH National Center for Advancing Translational Science, US Department of Veterans Affairs Research Enhancement Award Program (to FW, HPB and JG) and Career Development Award (to KPJ); International Bipolar Foundation (to HPB); Brain and Behavior Research Foundation (to FW, and HPB); Attias Family Foundation (to HPB); Klingenstein Third Generation Foundation (to FW); Women’s Health Research at Yale (to HPB); and The John and Hope Furth Endowment (to HPB). We thank Susan Quatrano and Philip Markovich for their assistance with the research; Cheryl Lacadie, Karen Martin, Terry Hickey and Hedy Sarofin for their technical expertise; Ann Marie Lacobelle for her genotyping assistance; Dr Andrew McIntosh for his comments on an earlier version of this manuscript; and the research subjects for their participation.

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  1. Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA

    E T C Lippard, K P Jensen, F Wang, J A Y Johnston, L Spencer, B Pittman, J Gelernter & H P Blumberg

  2. Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA

    E T C Lippard & H P Blumberg

  3. Department of Psychiatry, VA Connecticut Healthcare System, West Haven, CT, USA

    K P Jensen, J Gelernter & H P Blumberg

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Lippard, E., Jensen, K., Wang, F. et al. Effects of ANK3 variation on gray and white matter in bipolar disorder. Mol Psychiatry 22, 1345–1351 (2017). https://doi.org/10.1038/mp.2016.76

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