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|Title:||Genome-wide association study identifies SESTD1 as a novel risk gene for lithium-responsive bipolar disorder|
|Authors:||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|
|Publisher:||Nature Publishing Group|
|Description:||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.|
|Other Identifiers:||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.|
|Type Of Material:||Journal Article|
|Appears in Collections:||Harvard Medical School|
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