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. 2018 Jan 17;11(1):2.
doi: 10.1186/s12920-018-0321-6.

Insights into the genetics of blood pressure in black South African individuals: the Birth to Twenty cohort

Liesl M Hendry  1   2 , Venesa Sahibdeen  3 , Ananyo Choudhury  4 , Shane A Norris  5 , Michèle Ramsay  4   3 , Zané Lombard  6   3 ; of the AWI-Gen study and as members of the H3Africa Consortium
Affiliations

Insights into the genetics of blood pressure in black South African individuals: the Birth to Twenty cohort

Liesl M Hendry et al. BMC Med Genomics. .

Abstract

Background: Cardiovascular diseases (CVDs) are the leading cause of non-communicable disease deaths globally, with hypertension being a major risk factor contributing to CVDs. Blood pressure is a heritable trait, with relatively few genetic studies having been performed in Africans. This study aimed to identify genetic variants associated with variance in systolic (SBP) and diastolic (DBP) blood pressure in black South Africans.

Methods: Genotyping was performed using the Metabochip in a subset of participants (mixed sex; median age 17.9) and their adult female caregivers (median age 41.0) from the Birth to Twenty cohort (n = 1947). Data were analysed as a merged dataset (all participants and caregivers together) in GEMMA (v0.94.1) using univariate linear mixed models, incorporating a centered relatedness matrix to account for the relatedness between individuals and with adjustments for age, sex, BMI and principal components of the genotype information.

Results: Association analysis identified regions of interest in the NOS1AP (DBP: rs112468105 - p = 7.18 × 10-5 and SBP: rs4657181 - p = 4.04 × 10-5), MYRF (SBP: rs11230796 - p = 2.16 × 10-7, rs400075 - p = 2.88 × 10-7) and POC1B (SBP: rs770373 - p = 7.05 × 10-5, rs770374 - p = 9.05 × 10-5) genes and some intergenic regions (DACH1|LOC440145 (DBP: rs17240498 - p = 4.91 × 10-6 and SBP: rs17240498 - p = 2.10 × 10-5) and INTS10|LPL (SBP: rs55830938 - p = 1.30 × 10-5, rs73599609 - p = 5.78 × 10-5, rs73667448 - p = 6.86 × 10-5)).

Conclusions: The study provided further insight into the contribution of genetic variants to blood pressure in black South Africans. Future functional and replication studies in larger samples are required to confirm the role of the identified loci in blood pressure regulation and whether or not these variants are African-specific.

Keywords: Birth to Twenty; Metabochip; black South Africans; blood pressure; genetics.

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Conflict of interest statement

Ethics approval and consent to participate

Written assent was obtained from all participants at 13 years of age in conjunction with written consent from caregivers prior to blood sample collection. Written consent was obtained from participants when they were over 18 years of age. Ethical clearance was obtained from the University of the Witwatersrand Human Research Ethics Committee (Medical) for collection of DNA samples and phenotype data from this cohort (M010556). Further clearance was obtained for use of these samples to identify genetic risks associated with blood pressure (M1411116) in a black South African population.

Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Manhattan plots drawn from the association results (with correction for covariates and PCs where necessary). Plots are shown for association with (a) DBP and (b) SBP. The upper horizontal line indicates the calculated array-wide significance cutoff (p = 6.7 × 10−7) while the lower horizontal line shows the cutoff of p = 1 × 10−4. Identified regions of interest for further investigation are indicated by arrows. DACH1 – Dachshund Family Transcription Factor 1; INTS10 – integrator complex subunit 10; LPL – lipoprotein lipase; MYRF – myelin regulatory factor; NOS1AP – nitric oxide synthase 1 (neuronal) adaptor protein; POC1B – POC1 centriolar protein
Fig. 2
Fig. 2
LocusZoom plot for the association of rs112468105 (in NOS1AP) with DBP against a YRI LD background. rs112468105 is represented by a purple diamond. SNPs around this index SNP are coloured according to the LD between each SNP and the index SNP. SNPs with missing LD information are shown in grey. rs112468105 is monomorphic in the CEU population
Fig. 3
Fig. 3
LocusZoom plot for the association of rs4657181 (in NOS1AP) with SBP against a CEU LD background. rs4657181 is represented by a purple diamond. SNPs around this index SNP are coloured according to the LD between each SNP and the index SNP. SNPs with missing LD information are shown in grey. The plot shows evidence of high LD in this region in the CEU population. rs4657181 had completely missing LD information when drawn for the YRI population
Fig. 4
Fig. 4
LocusZoom plots for the association of rs11230796 (in MYRF) with SBP against (a) YRI and (b) CEU LD backgrounds. rs11230796 is represented by a purple diamond. SNPs around this index SNP are coloured according to the LD between each SNP and the index SNP. SNPs with missing LD information are shown in grey. MYRF is referred to by an alternative name (C11orf9) in this plot. The plot shows evidence of high LD in both the YRI and CEU populations between rs11230796 and the other SNP (rs400075) that has a strong association with SBP
Fig. 5
Fig. 5
LocusZoom plots for the association of rs770373 (in POC1B) with SBP against (a) YRI and (b) CEU LD backgrounds. rs770373 is represented by a purple diamond. SNPs around this index SNP are coloured according to the LD between each SNP and the index SNP. SNPs with missing LD information are shown in grey. POC1B is referred to by an alternative name (WDR51B) in this plot. The plot shows evidence of high LD in both the YRI and CEU populations between rs770373 and the other SNP (rs770374) that has a strong association with SBP
Fig. 6
Fig. 6
LocusZoom plot for the association of rs55830938 (intergenic to INTS10 and LPL) with SBP against a YRI LD background. rs55830938 is represented by a purple diamond. SNPs around this index SNP are coloured according to the LD between each SNP and the index SNP. SNPs with missing LD information are shown in grey. rs55830938 is monomorphic in the CEU population
See this image and copyright information in PMC

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