کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10302224 542704 2013 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A genome-wide association study of a sustained pattern of antidepressant response
ترجمه فارسی عنوان
بررسی یک رابطه ژنوم در یک الگوی پایدار پاسخ های ضد افسردگی
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی روانپزشکی بیولوژیکی
چکیده انگلیسی
Genome-wide association studies (GWAS) have failed to replicate common genetic variants associated with antidepressant response, as defined using a single endpoint. Genetic influences may be discernible by examining individual variation between sustained versus unsustained patterns of response, which may distinguish medication effects from non-specific, or placebo responses to active medication. We conducted a GWAS among 1116 subjects with Major Depressive Disorder from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial who were characterized using Growth Mixture Modeling as showing a sustained versus unsustained pattern of clinical response over 12 weeks of treatment with citalopram. Replication analyses examined 585 subjects from the Genome-based Therapeutic Drugs for Depression (GENDEP) trial. The strongest association with sustained as opposed to unsustained response in STAR*D involved a single nucleotide polymorphism (SNP; rs10492002) within the acyl-CoA synthetase short-chain family member 3 gene (ACSS3, p-value = 4.5 × 10−6, odds ratio = 0.61). No SNPs met our threshold for genome-wide significance. SNP data were available in GENDEP for 18 of the top 25 SNPs in STAR*D. The most replicable association was with SNP rs7816924 (p = 0.008, OR = 1.58); no SNP met the replication p-value threshold of 0.003. Joint analysis of these 18 SNPs resulted in the strongest signal coming from rs7816924 (p = 2.11 × 10−7), which resides in chondroitin sulfate N-acetylgalactosaminyltransferase 1 gene (CSGALNACT1). An exploratory genetic pathway analysis revealed evidence for an involvement of the KEGG pathway of long-term potentiation (FDR = .02). Results suggest novel genetic associations to sustained response.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Psychiatric Research - Volume 47, Issue 9, September 2013, Pages 1157-1165
نویسندگان
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