London School of Hygiene and Tropical Medicine, London, UK.
MRC/UVRI & LSHTM Uganda Research Unit, Entebbe, Uganda.
Mol Genet Genomic Med. 2019 Oct;7(10):e00950. doi: 10.1002/mgg3.950. Epub 2019 Aug 30.
Genetic association studies of blood pressure (BP) have mostly been conducted in non-African populations. Using the Entebbe Mother and Baby Study (EMaBS), we aimed to identify genetic variants associated with BP among Ugandan adolescents.
Systolic and diastolic BP were measured among 10- and 11-year olds. Whole-genome genotype data were generated using Illumina omni 2.5M arrays and untyped variants were imputed. Genome-wide association study (GWAS) was conducted using linear mixed model regression to account for population structure. Linear regression analysis was used to assess whether variants previously associated with BP (p < 5.0 × 10 ) in published BP GWASs were replicated in our study.
Of the 14 million variants analyzed among 815 adolescents, none reached genome-wide significance (p < 5.0×10 ) for association with systolic or diastolic BP. The most strongly associated variants were rs181430167 (p = 6.8 × 10 ) for systolic BP and rs12991132 (p = 4.0 × 10 ) for diastolic BP. Thirty-three (17 single nucleotide polymorphisms (SNPs) for systolic BP, 15 SNPs for diastolic BP and one SNP for both) of 330 variants previously identified as associated with BP were replicated in this study, but none remained significant after accounting for multiple testing.
Variants showing suggestive associations are worthy of future investigation. Replication results suggest that variants influencing adolescent BP may overlap somewhat with those already established in previous studies, largely based on adults in Western settings.
血压(BP)的遗传关联研究主要在非非洲人群中进行。利用恩德培母婴研究(EMaBS),我们旨在确定乌干达青少年中与 BP 相关的遗传变异。
在 10 至 11 岁的儿童中测量收缩压和舒张压。使用 Illumina omni 2.5M 阵列生成全基因组基因型数据,并对未分型变体进行了推断。使用线性混合模型回归进行全基因组关联研究(GWAS),以考虑人群结构。使用线性回归分析评估先前在已发表的 BP GWAS 中与 BP 相关的(p<5.0×10)变体是否在我们的研究中得到复制。
在 815 名青少年中分析的 1400 万个变体中,没有一个与收缩压或舒张压相关达到全基因组显着性(p<5.0×10)。与收缩压关联最强的变体是 rs181430167(p=6.8×10),与舒张压关联最强的变体是 rs12991132(p=4.0×10)。在这项研究中,先前确定与 BP 相关的 330 个变体中的 33 个(收缩压 17 个单核苷酸多态性(SNP),舒张压 15 个 SNP,一个 SNP 两者)得到了复制,但在进行多重检验后,没有一个仍然具有显着性。
显示提示性关联的变体值得进一步研究。复制结果表明,影响青少年 BP 的变体可能与先前在主要基于西方成年人的研究中已经确定的变体有一定程度的重叠。