Voluntary participation and informed consent to international genetic research.

Objectives: We compared voluntary participation and comprehension of informed consent among individuals of African ancestry enrolled in similarly designed genetic studies of hypertension in the United States and Nigeria.

Methods: Survey questionnaires were used to evaluate factors associated with voluntariness (the number of people volunteering) and understanding of the study's genetic purpose. A total of 655 individuals (United States: 348; Nigeria: 307) were interviewed after participation in the genetic studies.

Podoconiosis: a tropical model for gene-environment interactions?

Podoconiosis (endemic non-filarial elephantiasis) is a geochemical disease occurring in individuals exposed to red clay soil derived from alkalic volcanic rock. It is a chronic, debilitating disorder and a considerable public health problem in at least 10 countries in tropical Africa, Central America and northern India. Only a small proportion of individuals exposed to red clay develop disease and familial clustering of cases occurs, so we tested the hypothesis that disease occurs in genetically susceptible individuals on exposure to an environmental element in soil.

Genomewide scan and fine mapping of quantitative trait loci for intraocular pressure on 5q and 14q in West Africans.

Purpose: High intraocular pressure (IOP) is a major risk factor for glaucoma, one of the leading causes of blindness worldwide. Because it has been demonstrated that African populations are at increased risk for glaucoma, the authors investigated the genetic basis of IOP in a sample of West Africans with type 2 diabetes (T2D) from Ghana and Nigeria.

Methods: Genomewide linkage analysis was conducted for loci linked to IOP (measured by applanation tonometry) in 244 affected sibling pairs with T2D using 372 autosomal short-tandem repeat markers at an average spacing of 9 cM.

Computational disease gene identification: a concert of methods prioritizes type 2 diabetes and obesity candidate genes.

Genome-wide experimental methods to identify disease genes, such as linkage analysis and association studies, generate increasingly large candidate gene sets for which comprehensive empirical analysis is impractical. Computational methods employ data from a variety of sources to identify the most likely candidate disease genes from these gene sets. Here, we review seven independent computational disease gene prioritization methods, and then apply them in concert to the analysis of 9556 positional candidate genes for type 2 diabetes (T2D) and the related trait obesity.

Positive association between resting energy expenditure and weight gain in a lean adult population.

Background: Weight gain in adulthood is common, from modest gains in developing countries to substantial increases in Western societies. Evidence of the importance of energy expenditure in adult weight change has been limited to studies conducted in Pima Indians, in whom resting energy expenditure (REE) was found to be inversely associated with weight gain.

Objective: The aim was to determine whether REE was predictive of weight change in lean Nigerian adults.

Genome scan linkage analysis comparing microsatellites and single-nucleotide polymorphisms markers for two measures of alcoholism in chromosomes 1, 4, and 7.

Background: We analyzed 143 pedigrees (364 nuclear families) in the Collaborative Study on the Genetics of Alcoholism (COGA) data provided to the participants in the Genetic Analysis Workshop 14 (GAW14) with the goal of comparing results obtained from genome linkage analysis using microsatellite and with results obtained using SNP markers for two measures of alcoholism (maximum number of drinks -MAXDRINK and an electrophysiological measure from EEG -TTTH1). First, we constructed haplotype blocks by using the entire set of single-nucleotide polymorphisms (SNP) in chromosomes 1, 4, and 7. These chromosomes have shown linkage signals for MAXDRINK or EEG-TTTH1 in previous reports.

A genome wide quantitative trait linkage analysis for serum lipids in type 2 diabetes in an African population.

Lipid abnormalities are strongly linked with coronary heart disease and are common in type 2 diabetes. However, little is known about the genetic determinants of serum lipids in African populations. An autosomal genome scan was performed for linkage to five plasma lipid phenotypes (total cholesterol, triglycerides (TG), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C) and VLDL-cholesterol (VLDL-C)) in the Africa-America Diabetes Mellitus (AADM) study.

Genetic structure in four West African population groups.

Background: Africa contains the most genetically divergent group of continental populations and several studies have reported that African populations show a high degree of population stratification. In this regard, it is important to investigate the potential for population genetic structure or stratification in genetic epidemiology studies involving multiple African populations. The presences of genetic sub-structure, if not properly accounted for, have been reported to lead to spurious association between a putative risk allele and a disease.

Genetic effects on blood pressure localized to chromosomes 6 and 7.

Objective: To identify quantitative trait loci (QTL) contributing to the variation in blood pressure in a west African population.

Methods: We conducted a multi-stage genome scan in a population sample from rural Nigeria. A 10 centimorgan genome-wide screen for log-transformed systolic blood pressure (SBP) and diastolic blood pressure (DBP) was first performed based on 1054 individuals from 188 families.

Angiotensin-converting enzyme gene polymorphisms and obesity: an examination of three black populations.

We examined the association between obesity and 13 angiotensin-converting enzyme (ACE) gene polymorphisms, including the presence (I) or absence (D) of an Alu element in intron 16 (I/D polymorphism), and performed haplotype analysis using data collected from participants of a community survey of hypertension among blacks living in Ibadan, Nigeria; Spanish Town, Jamaica; and Chicago, IL. Transmission distortion of ACE gene polymorphisms and haplotypes from heterozygous parents to affected offspring was examined in each study population. To estimate haplotypes, polymorphisms were divided into three groups based on their position on the ACE gene.

Concurrent bacteraemia and malaria in febrile Nigerian infants.

In the tropics, febrile illnesses are often presumed to be due to malaria, because of its endemicity, and treatment can lead to delay in diagnosis or failure to detect severe infections such as bacteraemia. This study sought to determine the prevalence of bacteraemia and malaria parasitaemia in febrile post-neonatal infants (age 1-12 months) at the University College Hospital, Ibadan, Nigeria, and the bacterial aetiological agents of bacteraemia in the infants. Therefore, 102 infants aged 1-12 months who presented with fever with a negative history of antimicrobial use in the week prior to presentation were evaluated and had blood cultures done for the detection of aerobic organisms by standard methods and blood films for malaria parasites.

Calpain-10 gene polymorphisms and type 2 diabetes in West Africans: the Africa America Diabetes Mellitus (AADM) Study.

Purpose: To investigate whether the three single nucleotide polymorphisms (SNPs), SNP-43, -56, and -63 of CAPN10 were associated with type 2 diabetes in a West African cohort.

Methods: A total of 347 diabetic subjects and 148 unaffected controls from four ethnic groups in two West African countries were enrolled in this study. After genotyping three SNPs of CAPN10 and one SNP from CYP19, the allele, genotype, and haplotype frequencies as well as the odds ratios were calculated to test their association with type 2 diabetes.

Haplotypes produced from rare variants in the promoter and coding regions of angiotensinogen contribute to variation in angiotensinogen levels.

The most efficient study design to map genes underlying complex traits will be determined by assumptions about whether the genetic effects are likely to be due to relatively few common variants or multiple rare variants. To examine the possibility that rare variants may influence blood pressure, we sequenced a 6.8 kb region of the angiotensinogen (AGT) gene in 29 male Nigerians with high plasma AGT levels and 28 with low levels.

An international comparative study of blood pressure in populations of European vs. African descent.

Background: The consistent finding of higher prevalence of hypertension in US blacks compared to whites has led to speculation that African-origin populations are particularly susceptible to this condition. Large surveys now provide new information on this issue.

Methods: Using a standardized analysis strategy we examined prevalence estimates for 8 white and 3 black populations (N = 85,000 participants).

Association between evolutionary history of angiotensinogen haplotypes and plasma levels.

Over the last decade, considerable effort has been invested in studying the associations between angiotensinogen (AGT) variants, AGT plasma levels and high blood pressure. Evidence accumulated to date consistently supports the relationship between the AGT locus and the protein level, while an influence on blood pressure has been difficult to establish; in both instances the predisposing molecular variants are not fully defined. An evolutionary approach, taking into account the phylogenetic relationship between all the polymorphisms at this locus, may improve our understanding of the genetic nature of these quantitative phenotypes.

A genome scan among Nigerians linking resting energy expenditure to chromosome 16.

Energy requirements at rest account for 50% to 75% of total energy expenditure. Interindividual variation in resting energy expenditure (REE) has been studied for potential links to obesity and hypertension. REE is a modestly heritable trait, and yet virtually nothing is known about the genetic factors that might influence the familial patterns.

A genome-wide search for type 2 diabetes susceptibility genes in West Africans: the Africa America Diabetes Mellitus (AADM) Study.

The incidence of type 2 diabetes is growing rapidly, not only in developed countries but also worldwide. We chose to study type 2 diabetes in West Africa, where diabetes is less common than in the U.S.

Angiotensin I-converting enzyme polymorphisms, ACE level and blood pressure among Nigerians, Jamaicans and African-Americans.

The genes in the renin-angiotensin system are important physiologic candidates in studies of the genetic susceptibility to hypertension. Limited information has been available in most studies on the extent of variation in the candidate loci or the modifying effects of different environmental settings. We consequently genotyped 13 polymorphisms at the angiotensin I-converting enzyme (ACE) locus at an average distance of 2 kb in 2776 family members from Nigeria, Jamaica and an African-American community in the US.

Association between blood pressure and resting energy expenditure independent of body size.

Obesity is an important risk factor for hypertension; however, the pathway through which it raises blood pressure (BP) is poorly understood. Body size is also the primary determinant of energy expenditure, and we therefore examined the joint relationship of energy expenditure and body size to blood pressure. Resting energy expenditure (REE) was measured using respiratory gas exchange in population-based samples of 997 Nigerians and 452 African Americans.

Body composition of children in south-western Nigeria: validation of bio-electrical impedance analysis.

Bio-electrical impedance analysis (BIA) is a non-invasive method of estimating body composition and has the potential to be useful in clinics and for nutrition and health-related research in Africa. We sought to validate BIA for use among a Yoruba population in south-western Nigeria and to use BIA to assess the body composition of a healthy cohort of children. Total body water (TBW) was measured in 92 individuals (53 adults and 39 children) using deuterium dilution; height, weight and resistance were measured by BIA.

A genome-wide scan for body mass index among Nigerian families.

Objective: Interest in mapping genetic variants that are associated with obesity remains high because of the increasing prevalence of obesity and its complications worldwide. Data on genetic determinants of obesity in African populations are rare.

Research Methods And Procedures: We have undertaken a genome-wide scan for body mass index (BMI) in 182 Nigerian families that included 769 individuals.

Predictors of bacteraemia among febrile infants in Ibadan, Nigeria.

Fever is a common complaint in infancy, and bacteraemia is one of the more serious causes of such fever. However, there exists scanty data on risk of bacteraemia among febrile infants of developing countries and what clinical predictors, if any, could identify those febrile infants with bacteraemia. To address this issue, 102 infants aged 1-12 month(s) attending the Children's Emergency Ward of University College Hospital, Ibadan, Nigeria, with rectal temperatures of > or = 38 degrees C and with a negative history of antimicrobial use for at least one week prior to presentation, were studied to identify clinical predictors of bacteraemia.

Genome scan among Nigerians linking blood pressure to chromosomes 2, 3, and 19.

An understanding of the genetic influences on hypertension would help unravel the pathophysiology of this complex disorder and improve our understanding of causal mechanisms. Contemporary technology makes it possible to examine enough genetic markers to support a generalized search across the entire genome for candidate regions. In the present study, a family set was recruited from southwest Nigeria, and 378 microsatellite markers were typed on 792 individuals in 196 families.

Angiotensin-1-converting enzyme (ACE) plasma concentration is influenced by multiple ACE-linked quantitative trait nucleotides.

Circulating angiotensin-1-converting enzyme (ACE) is a highly heritable trait, and a major component of the genetic variance maps to the region of the ACE gene. The strong effect of the locus, and the interest in ACE as a candidate gene for cardiovascular disorders, has led to extensive investigation of its relationship to the ACE phenotype, providing one of the most complete examples of quantitative trait locus (QTL) analysis in humans. Resequencing of ACE followed by haplotype analysis in families of British and French origin has shown that the genetic variants that are primarily associated with the ACE trait map to an 18 kb interval flanked by two intragenic, ancestral recombination breakpoints.