Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Hum Genet. 2018 Apr;137(4):281-292. doi: 10.1007/s00439-018-1881-4. Epub 2018 Apr 10.
Genotype imputation estimates unobserved genotypes from genome-wide makers, to increase genome coverage and power for genome-wide association studies. Imputation has been successful for European ancestry populations in which very large reference panels are available. Smaller subsets of African descent populations are available in 1000 Genomes (1000G), the Consortium on Asthma among African ancestry Populations in the Americas (CAAPA) and the Haplotype Reference Consortium (HRC). We compared the performance of these reference panels when imputing variation in 3747 African Americans (AA) from two cohorts (HCV and COPDGene) genotyped using Illumina Omni microarrays. The haplotypes of 2504 (1000G), 883 (CAAPA) and 32,470 individuals (HRC) were used as reference. We compared the number of variants, imputation quality, imputation accuracy and coverage between panels. In both cohorts, 1000G imputed 1.5-1.6× more variants than CAAPA and 1.2× more than HRC. Similar findings were observed for variants with imputation R > 0.5 and for rare, low-frequency, and common variants. When merging imputed variants of the three panels, the total number was 62-63 M with 20 M overlapping variants imputed by all three panels, and a range of 5-15 M variants imputed exclusively with one of them. For overlapping variants, imputation quality was highest for HRC, followed by 1000G, then CAAPA, and improved as the minor allele frequency increased. 1000G, HRC and CAAPA provided high performance and accuracy for imputation of African American individuals, increasing the number of variants available for subsequent analyses. These panels are complementary and would benefit from the development of an integrated African reference panel.
基因型推断从全基因组标记推断未观测到的基因型，以增加全基因组关联研究的基因组覆盖率和效力。在具有非常大参考面板的欧洲血统人群中，推断已取得成功。在 1000 基因组（1000G）、美洲非洲裔人群哮喘联盟（CAAPA）和单倍型参考联盟（HRC）中，可用的较小的非洲裔亚群子集。我们比较了这些参考面板在推断来自两个队列（HCV 和 COPDGene）的 3747 名非裔美国人（AA）的变异时的性能，这些队列使用 Illumina Omni 微阵列进行了基因分型。2504 个人（1000G）、883 个人（CAAPA）和 32470 个人（HRC）的单倍型被用作参考。我们比较了变体数量、推断质量、推断准确性和覆盖范围。在两个队列中，1000G 推断的变体比 CAAPA 多 1.5-1.6 倍，比 HRC 多 1.2 倍。对于 R>0.5 的变体和罕见、低频和常见变体，观察到类似的发现。当合并三个面板的推断变体时，总数为 62-63 M，其中有 20 M 重叠变体被所有三个面板推断，范围为 5-15 M 变体仅被其中一个面板推断。对于重叠变体，HRC 的推断质量最高，其次是 1000G，然后是 CAAPA，并且随着次要等位基因频率的增加而提高。1000G、HRC 和 CAAPA 为非裔美国人个体的推断提供了高性能和准确性，增加了可用于后续分析的变体数量。这些面板是互补的，将受益于开发综合的非洲参考面板。
