Levin Albert M, Adrianto Indra, Datta Indrani, Iannuzzi Michael C, Trudeau Sheri, McKeigue Paul, Montgomery Courtney G, Rybicki Benjamin A
Department of Public Health Sciences, Henry Ford Health System, 1 Ford Place, 3E, 48202 Detroit, MI, USA.
BMC Genet. 2014 Jun 16;15:72. doi: 10.1186/1471-2156-15-72.
The expense of human leukocyte antigen (HLA) allele genotyping has motivated the development of imputation methods that use dense single nucleotide polymorphism (SNP) genotype data and the region's haplotype structure, but the performance of these methods in admixed populations (such as African Americans) has not been adequately evaluated. We compared genotype-based-derived from both genome-wide genotyping and targeted sequencing-imputation results to existing allele data for HLA-DRB1, -DQB1, and -DPB1.
In European Americans, the newly-developed HLA Genotype Imputation with Attribute Bagging (HIBAG) method outperformed HLAIMP:02. In African Americans, HLAIMP:02 performed marginally better than HIBAG pre-built models, but HIBAG models constructed using a portion of our African American sample with both SNP genotyping and four-digit HLA class II allele typing had consistently higher accuracy than HLA*IMP:02. However, HIBAG was significantly less accurate in individuals heterozygous for local ancestry (p ≤0.04). Accuracy improved in models with equal numbers of African and European chromosomes. Variants added by targeted sequencing and SNP imputation further improved both imputation accuracy and the proportion of high quality calls.
Combining the HIBAG approach with local ancestry and dense variant data can produce highly-accurate HLA class II allele imputation in African Americans.
人类白细胞抗原（HLA）等位基因基因分型的成本促使了利用密集单核苷酸多态性（SNP）基因型数据和区域单倍型结构的推断方法的发展，但这些方法在混合人群（如非裔美国人）中的性能尚未得到充分评估。我们将基于全基因组基因分型和靶向测序得出的基因型推断结果与HLA-DRB1、-DQB1和-DPB1的现有等位基因数据进行了比较。
在欧洲裔美国人中，新开发的带有属性装袋的HLA基因型推断（HIBAG）方法优于HLAIMP:02。在非裔美国人中，HLAIMP:02的表现略优于HIBAG预建模型，但使用我们一部分同时进行了SNP基因分型和四位数字HLA II类等位基因分型的非裔美国人样本构建的HIBAG模型始终比HLA*IMP:02具有更高的准确性。然而，HIBAG在本地血统杂合个体中的准确性显著较低（p≤0.04）。在具有相等数量非洲和欧洲染色体的模型中，准确性有所提高。靶向测序和SNP推断添加的变异进一步提高了推断准确性和高质量分型的比例。
将HIBAG方法与本地血统和密集变异数据相结合，可以在非裔美国人中产生高度准确的HLA II类等位基因推断。
