Suggestive linkage at 9p22 in bipolar disorder weighted by alcohol abuse.
Suggestive linkage at 9p22 in bipolar disorder weighted by alcohol abuse.
复制标题
双相情感障碍中 9p22 处的暗示性联系以酗酒为重。
DOI：
10.1002/ajmg.b.30937
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Zöllner,Sebastian
中科院分区：
文献类型：
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作者：
Saunders,ErikaFH;Zhang,Peng;Copeland,JNathan;Mclnnis,MelvinG;Zöllner,Sebastian
双相情感障碍 (BP) 是一种高度遗传性疾病，但绘制遗传风险因素的尝试具有挑战性。这些困难的一个可能原因是 BP 的遗传异质性。因此，关注临床同质家族来创建遗传上更同质的样本可能会增加发现特定变异的能力。酒精滥用 (AA) 和酒精依赖 (AD) 在 BP 家族中具有家族性，这些家族可能携带特定的 BP 风险变异。我们通过对国家心理健康遗传学研究所 BP 的 638 个家系（1,835 名个体）进行全基因组连锁扫描来测试这一假设，并根据家族 AA 或 AD 的频率对连锁证据进行加权。使用 AA 加权，我们在 9p22.2 上识别出一个连锁区域，NPL 得分为 3.23。该区域之前已在双相情感障碍关联的荟萃分析中被识别出来。我们使用排列分析来评估 AA 加权是否比偶然预期更多地增加了连锁信号，并观察到显着的 P 值 (P= 0.048)。因此，9p22.2 上的 BP 遗传风险因素在 AA 水平高的家庭中影响更大。总之，我们提出了一个使用 AA 和 AD 等协变量来定义 BP 亚型的示例，演示了如何使用此类亚型来提高连锁扫描的能力，并演示了验证所建议的相互作用的统计方法。 © 2009 Wiley-Liss, Inc.
Bipolar disorder (BP) is a highly heritable disorder, however attempts to map genetic risk factors are challenging. One possible reason for these difficulties is the genetic heterogeneity of BP. Hence, focusing on clinically homogeneous families to create a genetically more homogeneous sample may increase the power of finding a specific variant. Alcohol abuse (AA) and alcohol dependence (AD) are familial in BP families, and these families may carry a specific risk variant for BP. We tested this hypothesis by performing a genome‐wide linkage scan in 638 pedigrees (1,835 individuals) from the National Institute of Mental Health Genetics Initiative for BP, weighting the evidence for linkage according to the family's frequency of AA or AD. Using AA weighting, we identified a linkage region on 9p22.2 with an NPL score of 3.23. The region had previously been identified in a meta‐analysis of linkage in bipolar disorder. We used permutation analysis to assess if weighting by AA increased the linkage signal more than expected by chance and observed a significantP‐value (P= 0.048). Therefore, the genetic risk factor for BP on 9p22.2 has an increased effect in families with high levels of AA. In summary, we present an example of using covariates such as AA and AD to define subtypes of BP, demonstrate how using such subtypes can improve the power of a linkage scan, and demonstrate statistical approaches to validate the suggested interaction. © 2009 Wiley‐Liss, Inc.