Genome-wide association study identifies SESTD1 as a novel risk gene for lithium-responsive bipolar disorder

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Genome-wide association study identifies SESTD1 as a novel risk gene for lithium-responsive bipolar disorder

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Title: Genome-wide association study identifies SESTD1 as a novel risk gene for lithium-responsive bipolar disorder
Author: Song, J; Bergen, S E; Di Florio, A; Karlsson, R; Charney, A; Ruderfer, D M; Stahl, E A; Chambert, K D; Moran, J L; Gordon-Smith, K; Forty, L; Green, E K; Jones, I; Jones, L; Scolnick, E M; Sklar, P; Smoller, J W; Lichtenstein, P; Hultman, C; Craddock, N; Landén, M; Smoller, Jordan W; Perlis, Roy H; Lee, Phil Hyoun; Castro, Victor M; Hoffnagle, Alison G; Sklar, Pamela; Stahl, Eli A; Purcell, Shaun M; Ruderfer, Douglas M; Charney, Alexander W; Roussos, Panos; Michele Pato, Carlos Pato; Medeiros, Helen; Sobel, Janet; Craddock, Nick; Jones, Ian; Forty, Liz; Florio, Arianna Di; Green, Elaine; Jones, Lisa; Gordon-Smith, Katherine; Landen, Mikael; Hultman, Christina; Jureus, Anders; Bergen, Sarah; McCarroll, Steven; Moran, Jennifer; Chambert, Kimberly; Belliveau, Richard A

Note: Order does not necessarily reflect citation order of authors.

Citation: Song, J., S. E. Bergen, A. Di Florio, R. Karlsson, A. Charney, D. M. Ruderfer, E. A. Stahl, et al. 2016. “Genome-wide association study identifies SESTD1 as a novel risk gene for lithium-responsive bipolar disorder.” Molecular Psychiatry 21 (9): 1290-1297. doi:10.1038/mp.2015.165. http://dx.doi.org/10.1038/mp.2015.165.
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Abstract: Lithium is the mainstay prophylactic treatment for bipolar disorder (BD), but treatment response varies considerably across individuals. Patients who respond well to lithium treatment might represent a relatively homogeneous subtype of this genetically and phenotypically diverse disorder. Here, we performed genome-wide association studies (GWAS) to identify (i) specific genetic variations influencing lithium response and (ii) genetic variants associated with risk for lithium-responsive BD. Patients with BD and controls were recruited from Sweden and the United Kingdom. GWAS were performed on 2698 patients with subjectively defined (self-reported) lithium response and 1176 patients with objectively defined (clinically documented) lithium response. We next conducted GWAS comparing lithium responders with healthy controls (1639 subjective responders and 8899 controls; 323 objective responders and 6684 controls). Meta-analyses of Swedish and UK results revealed no significant associations with lithium response within the bipolar subjects. However, when comparing lithium-responsive patients with controls, two imputed markers attained genome-wide significant associations, among which one was validated in confirmatory genotyping (rs116323614, P=2.74 × 10−8). It is an intronic single-nucleotide polymorphism (SNP) on chromosome 2q31.2 in the gene SEC14 and spectrin domains 1 (SESTD1), which encodes a protein involved in regulation of phospholipids. Phospholipids have been strongly implicated as lithium treatment targets. Furthermore, we estimated the proportion of variance for lithium-responsive BD explained by common variants (‘SNP heritability') as 0.25 and 0.29 using two definitions of lithium response. Our results revealed a genetic variant in SESTD1 associated with risk for lithium-responsive BD, suggesting that the understanding of BD etiology could be furthered by focusing on this subtype of BD.
Published Version: doi:10.1038/mp.2015.165
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4995544/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:29407537
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