小柯机器人

美国哈佛大学Alkes L. Price和Wouter J. Peyrot合作使用CC-GWAS鉴定出八种精神疾病中具有不同等位基因频率的基因座。相关论文于2021年3月8日发表于国际学术期刊《自然—遗传学》。

研究人员开发了一种新方法（病例-病例全基因组关联研究； CC-GWAS），使用来自病例对照GWAS的汇总统计数据来检验两种疾病病例之间等位基因频率的差异，这超越了目前需要个体水平的方法数据。仿真和分析计算证实，CC-GWAS具有有效控制I型错误的强大功能。研究将CC-GWAS应用于精神分裂症、躁郁症、重度抑郁症和其他五种精神疾病的统计信息。

CC-GWAS确定了196个独立的病例-基因座，其中包括72个CC-GWAS-特异性基因座，这些基因在输入病例-对照总结统计中在全基因组水平上均不显著。两个CC-GWAS特异的基因座暗示了基因KLF6和KLF16（来自类似Krüppel的转录因子家族），这些基因与神经突生长和轴突再生有关。CC-GWAS基因座可在独立重复数据的使用中得到可靠重复。 

据介绍，精神疾病与遗传高度相关，但是关于疾病之间遗传差异的研究很少。

附：英文原文

Title: Identifying loci with different allele frequencies among cases of eight psychiatric disorders using CC-GWAS

Author: Wouter J. Peyrot, Alkes L. Price

Issue&Volume: 2021-03-08

Abstract: Psychiatric disorders are highly genetically correlated, but little research has been conducted on the genetic differences between disorders. We developed a new method (case–case genome-wide association study; CC-GWAS) to test for differences in allele frequency between cases of two disorders using summary statistics from the respective case–control GWAS, transcending current methods that require individual-level data. Simulations and analytical computations confirm that CC-GWAS is well powered with effective control of type I error. We applied CC-GWAS to publicly available summary statistics for schizophrenia, bipolar disorder, major depressive disorder and five other psychiatric disorders. CC-GWAS identified 196 independent case–case loci, including 72 CC-GWAS-specific loci that were not significant at the genome-wide level in the input case–control summary statistics; two of the CC-GWAS-specific loci implicate the genes KLF6 and KLF16 (from the Krüppel-like family of transcription factors), which have been linked to neurite outgrowth and axon regeneration. CC-GWAS loci replicated convincingly in applications to datasets with independent replication data.

DOI: 10.1038/s41588-021-00787-1

Source: https://www.nature.com/articles/s41588-021-00787-1

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex