Abstract
BackgroundGenetic 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.MethodsSystolic 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 × 10−8) in published BP GWASs were replicated in our study.ResultsOf the 14 million variants analyzed among 815 adolescents, none reached genome‐wide significance (p < 5.0×10−8) for association with systolic or diastolic BP. The most strongly associated variants were rs181430167 (p = 6.8 × 10−7) for systolic BP and rs12991132 (p = 4.0 × 10−7) 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.ConclusionVariants 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.
Highlights
Genome‐wide association studies (GWAS) predominantly from Caucasian and Asian populations have identified several single nucleotide polymorphisms (SNPs) associated with blood pressure (BP; Cho et al, 2009; Evangelou et al, 2018; Levy et al, 2009; Qian, Lu, Tan, Liu, & Lu, 2007; Warren et al, 2017; Xi et al, 2014)
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
Blood pressure Genome‐wide association study (GWAS) conducted among populations of African origin in the diaspora are rare, and often report different variants associated with BP compared to those reported in non‐African populations (Adeyemo et al, 2009; Fox et al, 2011; Franceschini et al, 2013; Kidambi et al, 2012; Liang et al, 2017)
Summary
Genome‐wide association studies (GWAS) predominantly from Caucasian and Asian populations have identified several single nucleotide polymorphisms (SNPs) associated with blood pressure (BP; Cho et al, 2009; Evangelou et al, 2018; Levy et al, 2009; Qian, Lu, Tan, Liu, & Lu, 2007; Warren et al, 2017; Xi et al, 2014). Among 38 studies that investigated genetic polymorphisms associated with hypertension in Africa‐based populations (participant numbers ranging from 65 to 1939) reviewed in (Yako et al, 2018), all adopted a candidate gene approach rather than conducting a GWAS. It remains unclear whether variants associated with BP in non‐African populations influence BP among Africans or whether the patterns of genetic susceptibility differ markedly. 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
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