Department of Psychology and Neuroscience, University of Colorado, Boulder, CO 80302, USA.
Am J Hum Genet. 2013 Sep 5;93(3):463-70. doi: 10.1016/j.ajhg.2013.07.007. Epub 2013 Aug 15.
To investigate the extent to which the proportion of schizophrenia's additive genetic variation tagged by SNPs is shared by populations of European and African descent, we analyzed the largest combined African descent (AD [n = 2,142]) and European descent (ED [n = 4,990]) schizophrenia case-control genome-wide association study (GWAS) data set available, the Molecular Genetics of Schizophrenia (MGS) data set. We show how a method that uses genomic similarities at measured SNPs to estimate the additive genetic correlation (SNP correlation [SNP-rg]) between traits can be extended to estimate SNP-rg for the same trait between ethnicities. We estimated SNP-rg for schizophrenia between the MGS ED and MGS AD samples to be 0.66 (SE = 0.23), which is significantly different from 0 (p(SNP-rg = 0) = 0.0003), but not 1 (p(SNP-rg = 1) = 0.26). We re-estimated SNP-rg between an independent ED data set (n = 6,665) and the MGS AD sample to be 0.61 (SE = 0.21, p(SNP-rg = 0) = 0.0003, p(SNP-rg = 1) = 0.16). These results suggest that many schizophrenia risk alleles are shared across ethnic groups and predate African-European divergence.
为了探究在多大程度上,单核苷酸多态性(SNP)标记的精神分裂症的加性遗传变异比例,在欧洲和非洲血统的人群中是共有的,我们分析了现有的最大的非洲裔(AD [n = 2142])和欧洲裔(ED [n = 4990])精神分裂症病例对照全基因组关联研究(GWAS)数据集,即精神分裂症分子遗传学(MGS)数据集。我们展示了如何使用测量 SNP 处的基因组相似性来估计性状之间的加性遗传相关(SNP 相关性[SNP-rg])的方法可以扩展到估计种族之间相同性状的 SNP-rg。我们估计了 MGS ED 和 MGS AD 样本之间精神分裂症的 SNP-rg 为 0.66(SE = 0.23),这与 0 显著不同(p(SNP-rg = 0)= 0.0003),但与 1 不同(p(SNP-rg = 1)= 0.26)。我们重新估计了独立 ED 数据集(n = 6665)和 MGS AD 样本之间的 SNP-rg 为 0.61(SE = 0.21,p(SNP-rg = 0)= 0.0003,p(SNP-rg = 1)= 0.16)。这些结果表明,许多精神分裂症风险等位基因在不同种族群体中是共有的,并且早于非洲-欧洲分化。