Genetic Association of Recovery from Eating Disorders: The Role of GABA Receptor SNPs
Genetic Association of Recovery from Eating Disorders: The Role of GABA Receptor SNPs
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DOI：
10.1038/npp.2011.108
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发表时间：
2011-10-01
影响因子：
7.6
通讯作者：
Kaye, Walter H.
中科院分区：
文献类型：
--
作者：
Bloss, Cinnamon S.;Berrettini, Wade;Kaye, Walter H.
对进食障碍（ED）的随访研究表明，结果从恢复到慢性疾病或死亡不等，但结果的预测因素尚未得到一致的确定。我们在1878名妇女中检测了约350个候选基因中的5151个单核苷酸多态性（SNP）与艾德恢复的相关性。最初的分析集中在一个严格定义的发现队列中，这些女性年龄超过25岁，终生诊断为艾德，并且可以获得关于艾德症状存在（n = 361，过去一年中持续存在症状，即“患病”）或不存在（n = 115，过去一年中无症状，即“痊愈”）的数据。GABRG 1中的内含子SNP（rs 17536211）显示出最强的相关统计学证据（p = 4.63 x 10（-6），错误发现率（FDR）= 0.021，比值比（OR）= 0.46）。我们在一个更自由定义的25岁或以下女性队列中重复了这些发现（n = 464例患病，n = 107例痊愈; p = 0.0336，OR = 0.68;合并样本p = 4.57 x 10（-6），FDR = 0.0049，OR = 0.55）。富集分析显示，GABA（γ-氨基丁酸）SNP在发现组（Z = 3.64，p = 0.0003）和合并组（Z = 2.07，p = 0.0388）中p <0.05相关的SNP中过度表达。在第三个独立队列（n = 154例艾德病例，n = 677例对照）的随访表型关联分析中，rs 17536211与特质焦虑相关（p = 0.049），表明该变异可能影响艾德结局的可能机制。这些发现可以为针对最难治疗的患者制定更有效的干预措施提供新的见解。Neuropsychopharmacology（2011）36，2222-2232; doi：10.1038/npp. 2011.108; 2011年7月13日在线发布
Follow-up studies of eating disorders (EDs) suggest outcomes ranging from recovery to chronic illness or death, but predictors of outcome have not been consistently identified. We tested 5151 single-nucleotide polymorphisms (SNPs) in approximately 350 candidate genes for association with recovery from ED in 1878 women. Initial analyses focused on a strictly defined discovery cohort of women who were over age 25 years, carried a lifetime diagnosis of an ED, and for whom data were available regarding the presence (n = 361 ongoing symptoms in the past year, ie, 'ill') or absence (n = 115 no symptoms in the past year, ie, 'recovered') of ED symptoms. An intronic SNP (rs17536211) in GABRG1 showed the strongest statistical evidence of association (p = 4.63 x 10(-6), false discovery rate (FDR) = 0.021, odds ratio (OR) = 0.46). We replicated these findings in a more liberally defined cohort of women age 25 years or younger (n = 464 ill, n = 107 recovered; p = 0.0336, OR = 0.68; combined sample p = 4.57 x 10(-6), FDR = 0.0049, OR = 0.55). Enrichment analyses revealed that GABA (gamma-aminobutyric acid) SNPs were over-represented among SNPs associated at po0.05 in both the discovery (Z = 3.64, p = 0.0003) and combined cohorts (Z = 2.07, p = 0.0388). In follow-up phenomic association analyses with a third independent cohort (n = 154 ED cases, n = 677 controls), rs17536211 was associated with trait anxiety (p = 0.049), suggesting a possible mechanism through which this variant may influence ED outcome. These findings could provide new insights into the development of more effective interventions for the most treatment-resistant patients. Neuropsychopharmacology (2011) 36, 2222-2232; doi: 10.1038/npp. 2011.108; published online 13 July 2011