دورية أكاديمية
Genome-wide association study identifies SESTD1 as a novel risk gene for lithium-responsive bipolar disorder.
| العنوان: | Genome-wide association study identifies SESTD1 as a novel risk gene for lithium-responsive bipolar disorder. |
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| المؤلفون: | Song, J, Bergen, SE, Di Florio, A, Karlsson, R, Charney, A, Ruderfer, DM, Stahl, EA, Members of the International Cohort Collection for Bipolar Disorder (ICCBD), Chambert, KD, Moran, JL, Gordon-Smith, K, Forty, L, Green, EK, Jones, I, Jones, L, Scolnick, EM, Sklar, P, Smoller, JW, Lichtenstein, P, Hultman, C, Craddock, N, Landén, M, Perlis, RH, Lee, PH, Castro, VM, Hoffnagle, AG, Purcell, SM, Charney, AW, Roussos, P, Michele Pato, CP, Medeiros, H, Sobel, J, Florio, AD, Green, E, Landen, M, Jureus, A, Bergen, S, McCarroll, S, Moran, J, Chambert, K, Belliveau, RA |
| بيانات النشر: | England |
| سنة النشر: | 2016 |
| المجموعة: | PEARL (Plymouth Electronic Archiv & ResearchLibrary, Plymouth University) |
| مصطلحات موضوعية: | Adult, Antimanic Agents, Biomarkers, Pharmacological, Bipolar Disorder, Carrier Proteins, Female, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Genotype, Humans, Lithium, Lithium Compounds, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Self Report, Sweden, United Kingdom |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 1290 - 1297 |
| اللغة: | English |
| تدمد: | 1476-5578 |
| العلاقة: | E-ISSN:1476-5578; http://hdl.handle.net/10026.1/8046Test |
| DOI: | 10.1038/mp.2015.165 |
| الإتاحة: | https://doi.org/10.1038/mp.2015.165Test http://hdl.handle.net/10026.1/8046Test |
| حقوق: | No embargo |
| رقم الانضمام: | edsbas.BCF87982 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 14765578 |
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| DOI: | 10.1038/mp.2015.165 |