Genetic Association for Renal Traits among Participants of African Ancestry Reveals New Loci for Renal Function

Chronic kidney disease (CKD) is an increasing global public health concern, particularly among populations of African ancestry. We performed an interrogation of known renal loci, genome-wide association (GWA), and IBC candidate-gene SNP association analyses in African Americans from the CARe Renal Consortium. In up to 8,110 participants, we performed meta-analyses of GWA and IBC array data for estimated glomerular filtration rate (eGFR), CKD (eGFR <60 mL/min/1.73 m2), urinary albumin-to-creatinine ratio (UACR), and microalbuminuria (UACR >30 mg/g) and interrogated the 250 kb flanking region around 24 SNPs previously identified in European Ancestry renal GWAS analyses. Findings were replicated in up to 4,358 African Americans. To assess function, individually identified genes were knocked down in zebrafish embryos by morpholino antisense oligonucleotides. Expression of kidney-specific genes was assessed by in situ hybridization, and glomerular filtration was evaluated by dextran clearance. Overall, 23 of 24 previously identified SNPs had direction-consistent associations with eGFR in African Americans, 2 of which achieved nominal significance (UMOD, PIP5K1B). Interrogation of the flanking regions uncovered 24 new index SNPs in African Americans, 12 of which were replicated (UMOD, ANXA9, GCKR, TFDP2, DAB2, VEGFA, ATXN2, GATM, SLC22A2, TMEM60, SLC6A13, and BCAS3). In addition, we identified 3 suggestive loci at DOK6 (p-value = 5.3×10−7) and FNDC1 (p-value = 3.0×10−7) for UACR, and KCNQ1 with eGFR (p = 3.6×10−6). Morpholino knockdown of kcnq1 in the zebrafish resulted in abnormal kidney development and filtration capacity. We identified several SNPs in association with eGFR in African Ancestry individuals, as well as 3 suggestive loci for UACR and eGFR. Functional genetic studies support a role for kcnq1 in glomerular development in zebrafish

Ethical and legal implications of whole genome and whole exome sequencing in African populations

BACKGROUND: Rapid advances in high throughput genomic technologies and next generation sequencing are making medical genomic research more readily accessible and affordable, including the sequencing of patient and control whole genomes and exomes in order to elucidate genetic factors underlying disease. Over the next five years, the Human Heredity and Health in Africa (H3Africa) Initiative, funded by the Wellcome Trust (United Kingdom) and the National Institutes of Health (United States of America), will contribute greatly towards sequencing of numerous African samples for biomedical research. DISCUSSION: Funding agencies and journals often require submission of genomic data from research participants to databases that allow open or controlled data access for all investigators. Access to such genotype-phenotype and pedigree data, however, needs careful control in order to prevent identification of individuals or families. This is particularly the case in Africa, where many researchers and their patients are inexperienced in the ethical issues accompanying whole genome and exome research; and where an historical unidirectional flow of samples and data out of Africa has created a sense of exploitation and distrust. In the current study, we analysed the implications of the anticipated surge of next generation sequencing data in Africa and the subsequent data sharing concepts on the protection of privacy of research subjects. We performed a retrospective analysis of the informed consent process for the continent and the rest-of-the-world and examined relevant legislation, both current and proposed. We investigated the following issues: (i) informed consent, including guidelines for performing culturally-sensitive next generation sequencing research in Africa and availability of suitable informed consent documents; (ii) data security and subject privacy whilst practicing data sharing; (iii) conveying the implications of such concepts to research participants in resource limited settings. SUMMARY: We conclude that, in order to meet the unique requirements of performing next generation sequencing-related research in African populations, novel approaches to the informed consent process are required. This will help to avoid infringement of privacy of individual subjects as well as to ensure that informed consent adheres to acceptable data protection levels with regard to use and transfer of such information

Patency of the Ductus Arteriosus in Newborns: Experience in a Special Care Baby Unit

A prospective cohort study of infants admitted into the Special Care Baby Unit, University College Hospital, Ibadan, has revealed a 24.5 per cent prevalence of patency of the ductus arteriosus (PDA) among 97 infants, who were admitted over a six-month period. The major factor predisposing to PDA was prematurity (p=0.014). A higher incidence of PDA (35 per cent) was found among the preterm infants, and of these preterm infants, the very low birth weight (VLBW) infants were found to be more highly susceptible to PDA (p = 0.028). The mean birth weight of the preterm infants who developed PDA in the study was 1447g, while that of those preterm infants without PDA was 1835g. There was no relationship between the sex of the infants and the development of PDA. A strong association was however, found between respiratory distress and PDA (

Examining for an association between candidate gene polymorphisms in the metabolic syndrome components on excess weight and adiposity measures in youth: a cross-sectional study

ABSTRACT: A polymorphism in a gene may exert its effects on multiple phenotypes. The aim of this study is to explore the association of 10 metabolic syndrome candidate genes with excess weight and adiposity and evaluate the effect of perinatal and socioeconomic factors on these associations. Methods: The anthropometry, socioeconomic and perinatal conditions and 10 polymorphisms were evaluated in 1081 young people between 10 and 18 years old. Genotypic associations were calculated using logistic and linear models adjusted by age, gender, and pubertal maturation, and a genetic risk score (GRS) was calculated by summing the number of effect alleles. Results: We found that AGT-rs699 and the IRS2-rs1805097 variants were significantly associated with excess weight, OR = 1.25 (CI 95% 1.01–1.54; p = 0.034); OR = 0.77 (CI 95% 0.62–0.96; p = 0.022), respectively. AGT-rs699 and FTO-rs17817449 variants were significantly and directly associated with body mass index (BMI) (p = 0.036 and p = 0.031), while IRS2-rs1805097 and UCP3-rs1800849 were significantly and negatively associated with BMI and waist circumference, correspondingly. Each additional effect allele in GRS was associated with an increase of 0.020 log(BMI) (p = 0.004). No effects from the socioeconomic and perinatal factors evaluated on the association of the candidate genes with the phenotypes were detected. Conclusions: Our observation suggests that AGT-rs699 and FTO-rs17817449 variants may contribute to the risk development of excess weight and an increase in the BMI, while IRS2-rs1805097 showed a protector effect; in addition, UCP3- rs1800849 showed a decreasing waist circumference. Socioeconomic and perinatal factors had no effect on the associations of the candidate gene