Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, USA.
Slone Epidemiology Center, Boston University, Boston, MA, USA.
Hum Genet. 2018 Jul;137(6-7):535-542. doi: 10.1007/s00439-018-1908-x. Epub 2018 Jul 13.
Several genome-wide association studies (GWAS) have identified genetic variants associated with birth weight. To date, however, most GWAS of birth weight have focused primarily on European ancestry samples even though prevalence of low birth weight is higher among African-Americans. We conducted admixture mapping using 2918 ancestral informative markers in 2596 participants of the Black Women's Health Study, with the goal of identifying novel genomic regions where local African ancestry is associated with birth weight. In addition, we performed a replication analysis of 11 previously identified index single nucleotide polymorphisms (SNPs), and fine-mapped those genetic loci to identify better or new genetic variants associated with birth weight in African-Americans. We found that high African ancestry at 12q14 was associated with low birth weight, and we identified multiple independent birth weight-lowering variants in this genomic region. We replicated the association of a previous GWAS SNP in ADRB1 and our fine-mapping efforts suggested the presence of new birth weight-associated variants in ADRB1, HMGA2, and SLC2A4. Further studies are needed to determine whether birth weight-associated loci can in part explain race-associated birth weight disparities.
几项全基因组关联研究（GWAS）已经确定了与出生体重相关的遗传变异。然而，迄今为止，大多数出生体重的 GWAS 主要集中在欧洲血统样本上，尽管非裔美国人的低出生体重发生率更高。我们使用 2596 名黑人妇女健康研究参与者中的 2918 个祖先信息标记进行了混合映射，目的是确定与出生体重相关的新的基因组区域，其中本地非洲血统与出生体重相关。此外，我们对 11 个先前确定的索引单核苷酸多态性（SNP）进行了复制分析，并对这些遗传基因座进行了精细映射，以确定与非裔美国人出生体重相关的更好或新的遗传变异。我们发现 12q14 上的高非洲血统与低出生体重有关，并且在该基因组区域中鉴定出多个独立的降低出生体重的变异。我们复制了 ADRB1 中先前 GWAS SNP 的关联，并且我们的精细映射工作表明 ADRB1、HMGA2 和 SLC2A4 中存在新的与出生体重相关的变异。需要进一步的研究来确定与出生体重相关的基因座是否可以在一定程度上解释与种族相关的出生体重差异。
