Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
Am J Med Genet B Neuropsychiatr Genet. 2013 Jul;162B(5):439-51. doi: 10.1002/ajmg.b.32168. Epub 2013 May 31.
Several aspects of sleep behavior such as timing, duration and quality have been demonstrated to be heritable. To identify common variants that influence sleep traits in the population, we conducted a genome-wide association study of six sleep phenotypes assessed by questionnaire in a sample of 2,323 individuals from the Australian Twin Registry. Genotyping was performed on the Illumina 317, 370, and 610K arrays and the SNPs in common between platforms were used to impute non-genotyped SNPs. We tested for association with more than 2,000,000 common polymorphisms across the genome. While no SNPs reached the genome-wide significance threshold, we identified a number of associations in plausible candidate genes. Most notably, a group of SNPs in the third intron of the CACNA1C gene ranked as most significant in the analysis of sleep latency (P = 1.3 × 10⁻⁶). We attempted to replicate this association in an independent sample from the Chronogen Consortium (n = 2,034), but found no evidence of association (P = 0.73). We have identified several other suggestive associations that await replication in an independent sample. We did not replicate the results from previous genome-wide analyses of self-reported sleep phenotypes after correction for multiple testing.
睡眠行为的几个方面，如时间、持续时间和质量，已经被证明是可以遗传的。为了确定影响人群睡眠特征的常见变异，我们对澳大利亚双胞胎登记处的 2323 名个体的六个睡眠表型进行了全基因组关联研究，这些表型通过问卷调查进行评估。在 Illumina 317、370 和 610K 芯片上进行基因分型，并用平台之间的常见 SNPs 对未分型的 SNPs 进行了推断。我们对整个基因组中超过 200 万个常见多态性进行了关联测试。虽然没有 SNP 达到全基因组显著性阈值，但我们在合理的候选基因中发现了一些关联。最值得注意的是，CACNA1C 基因第三个内含子中的一组 SNP 在睡眠潜伏期分析中排名最为显著（P = 1.3×10⁻⁶）。我们试图在 Chronogen 联盟的一个独立样本中复制这种关联（n = 2034），但没有发现关联的证据（P = 0.73）。我们还发现了其他一些需要在独立样本中复制的提示性关联。我们没有在经过多次测试校正后复制先前关于自我报告睡眠表型的全基因组分析的结果。
