Outpatient Clinic for Anxiety Disorders, Yokohama Clinic, Yokohama, Japan.
J Hum Genet. 2011 Dec;56(12):852-6. doi: 10.1038/jhg.2011.117. Epub 2011 Oct 20.
Family and twin studies have indicated that genetic factors have an important role in panic disorder (PD), whereas its pathogenesis has remained elusive. We conducted a genome-wide copy number variation (CNV) association study to elucidate the involvement of structural variants in the etiology of PD. The participants were 2055 genetically unrelated Japanese people (535 PD cases and 1520 controls). CNVs were detected using Genome-Wide Human SNP array 6.0, determined by Birdsuite and confirmed by PennCNV. They were classified as rare CNVs (found in <1% of the total sample) or common CNVs (found in ≥5%). PLINK was used to perform global burden analysis for rare CNVs and association analysis for common CNVs. The sample yielded 2039 rare CNVs and 79 common CNVs. Significant increases in the rare CNV burden in PD cases were not found. Common duplications in 16p11.2 showed Bonferroni-corrected P-values <0.05. Individuals with PD did not exhibit an increased genome-wide rare CNV burden. Common duplications were associated with PD and found in the pericentromeric region of 16p11.2, which had been reported to be rich in low copy repeats and to harbor developmental disorders, neuropsychiatric disorders and dysmorphic features.
家系和双胞胎研究表明，遗传因素在惊恐障碍（PD）中起着重要作用，但其发病机制仍不清楚。我们进行了全基因组拷贝数变异（CNV）关联研究，以阐明结构变异在 PD 发病机制中的作用。参与者为 2055 名无遗传关系的日本人（535 例 PD 病例和 1520 名对照）。使用基因组宽人类 SNP 阵列 6.0 检测 CNV，由 Birdsuite 确定，并由 PennCNV 确认。它们被分为罕见 CNV（在总样本中发现<1%）或常见 CNV（发现于≥5%）。PLINK 用于进行罕见 CNV 的全基因组负担分析和常见 CNV 的关联分析。该样本产生了 2039 个罕见 CNV 和 79 个常见 CNV。未发现 PD 病例中罕见 CNV 负担的显著增加。16p11.2 中的常见重复显示经 Bonferroni 校正的 P 值<0.05。PD 个体未表现出全基因组罕见 CNV 负担增加。常见重复与 PD 相关，位于 16p11.2 的着丝粒周围区域，该区域富含低拷贝重复序列，并且与发育障碍、神经精神障碍和畸形特征有关。
