Terrence Forrester

Estimating African American Admixture Proportions by Use of Population-Specific Alleles

We analyzed the European genetic contribution to 10 populations of African descent in the United States (Maywood, Illinois; Detroit; New York; Philadelphia; Pittsburgh; Baltimore; Charleston, South Carolina; New Orleans; and Houston) and in Jamaica, using nine autosomal DNA markers. These markers either are population-specific or show frequency differences >45% between the parental populations and are thus especially informative for admixture. European genetic ancestry ranged from 6.8% (Jamaica) to 22.5% (New Orleans). The unique utility of these markers is reflected in the low variance associated with these admixture estimates (SEM 1.3%-2.7%). We also estimated the male and female European contribution to African Americans, on the basis of informative mtDNA (haplogroups H and L) and Y Alu polymorphic markers. Results indicate a sex-biased gene flow from Europeans, the male contribution being substantially greater than the female contribution. mtDNA haplogroups analysis shows no evidence of a significant maternal Amerindian contribution to any of the 10 populations. We detected significant nonrandom association between two markers located 22 cM apart (FY-null and AT3), most likely due to admixture linkage disequilibrium created in the interbreeding of the two parental populations. The strength of this association and the substantial genetic distance between FY and AT3 emphasize the importance of admixed populations as a useful resource for mapping traits with different prevalence in two parental populations.

The prevalence of hypertension in seven populations of west African origin.

OBJECTIVES This study was undertaken to describe the distribution of blood pressures, hypertension prevalence, and associated risk factors among seven populations of West African origin. METHODS The rates of hypertension in West Africa (Nigeria and Cameroon), the Caribbean (Jamaica, St. Lucia, Barbados), and the United States (metropolitan Chicago, Illinois) were compared on the basis of a highly standardized collaborative protocol. After researchers were given central training in survey methods, population-based samples of 800 to 2500 adults over the age of 25 were examined in seven sites, yielding a total sample of 10014. RESULTS A consistent gradient of hypertension prevalence was observed, rising from 16% in West Africa to 26% in the Caribbean and 33% in the United States. Mean blood pressures were similar among persons aged 25 to 34, while the increase in hypertension prevalence with age was twice as steep in the United States as in Africa. Environmental factors, most notably obesity and the intake of sodium and potassium, varied consistently with disease prevalence across regions. CONCLUSION The findings demonstrate the determining role of social conditions in the evolution of hypertension risk in these populations.

Towards a new developmental synthesis: adaptive developmental plasticity and human disease

1focusing mainly on short-term outcomes such as infant survival and stunting. 2 However, the longer term eff ects on adult health 3 of a poor start to life suggest a further perspective. Developmental eff ects have been viewed traditionally in the context of major disruptions such as caused by teratogens, prematurity and growth retardation, but there is increasing appreciation of the role of developmental plasticity, which provides individuals with the fl exibility to adjust their trajectory of development to match their environment. Plasticity operates across the entire range of environment, from undernutrition to excessive nutritional environments associated with gestational diabetes or maternal obesity, 4,5

Genome-Wide Association Study of Coronary Heart Disease and Its Risk Factors in 8,090 African Americans: The NHLBI CARe Project

Coronary heart disease (CHD) is the leading cause of mortality in African Americans. To identify common genetic polymorphisms associated with CHD and its risk factors (LDL- and HDL-cholesterol (LDL-C and HDL-C), hypertension, smoking, and type-2 diabetes) in individuals of African ancestry, we performed a genome-wide association study (GWAS) in 8,090 African Americans from five population-based cohorts. We replicated 17 loci previously associated with CHD or its risk factors in Caucasians. For five of these regions (CHD: CDKN2A/CDKN2B; HDL-C: FADS1-3, PLTP, LPL, and ABCA1), we could leverage the distinct linkage disequilibrium (LD) patterns in African Americans to identify DNA polymorphisms more strongly associated with the phenotypes than the previously reported index SNPs found in Caucasian populations. We also developed a new approach for association testing in admixed populations that uses allelic and local ancestry variation. Using this method, we discovered several loci that would have been missed using the basic allelic and global ancestry information only. Our conclusions suggest that no major loci uniquely explain the high prevalence of CHD in African Americans. Our project has developed resources and methods that address both admixture- and SNP-association to maximize power for genetic discovery in even larger African-American consortia.

Fetal growth and cardiovascular risk factors in Jamaican schoolchildren

Abstract Objective: To determine relation between schoolchildrens blood pressure, glycated haemoglobin level, and cholesterol concentration and their anthropometry, socioeconomic status, and birth measurements. Design: Retrospective cohort study. Setting: 27 schools closest to University Hospital of the West Indies, Kingston, Jamaica. Subjects: 2337 children aged 6-16 years who were born at university hospital were recruited, and their birth records were recovered: 1610 had suitable records, 659 had records including birth length, and 610 of these were prepubertal. Main outcome measures: Blood pressure, glycated haemoglobin level, serum cholesterol concentration, anthropometry at birth, current anthropometry, and socioeconomic status. Results: Multiple regression analysis showed that childrens systolic blood pressure was inversely related to their birth weight (P<0.0001) and directly related to their current weight. Glycated haemoglobin level was higher in children with thicker triceps skinfolds (P<0.001) and who had been shorter at birth (P=0.003). Serum cholesterol concentration was inversely related to current height (P=0.001) and to length at birth (P=0.09) and was directly related to triceps skinfold thickness and higher socioeconomic status (P<0.001). Conclusions: Blood pressure in childhood was inversely related to birth weight and directly to current weight. Glycaemic control and serum cholesterol were related to short length at birth, height deficit in childhood, and childhood obesity.

Maternal nutritional status in pregnancy and blood pressure in childhood.

Objective To examine the relation between indices of maternal nutrition during pregnancy, including haemoglobin concentration, skinfold thickness and body weight, and the childs blood pressure at 10 to 12 years of age.

Prevalence of NIDDM Among Populations of the African Diaspora

OBJECTIVE Rates of non-insulin-dependent diabetes mellitus have risen sharply in recent years among blacks in the U.S. and the U.K. Increases in risk have likewise been observed in the island nations of the Caribbean and in urban West Africa. To date, however, no systematic comparison of the geographic variation of NIDDM among black populations has been undertaken. RESEARCH DESIGN AND METHODS In the course of an international collaborative study on cardiovascular disease, we used a standardized protocol to determine the rates of NIDDM and associated risk factors in populations of the African diaspora. Representative samples were drawn from sites in Nigeria, St. Lucia, Barbados, Jamaica, the United States, and the United Kingdom. A total of 4,823 individuals aged 25–74 years were recruited, all sites combined. RESULTS In sharp contrast to a prevalence of 2% in Nigeria, age-adjusted prevalences of self-reported NIDDM were 9% in the Caribbean and 11% in the U.S. and the U.K. Mean BMI ranged from 22 kg/m2 among men in West Africa to 31 kg/m2 in women in the U.S. Disease prevalence across sites was essentially collinear with obesity, pointing to site differences in the balance between energy intake and expenditure as the primary determinant of differential NIDDM risk among these populations. CONCLUSIONS In ethnic groups sharing a common genetic ancestry, these comparative data demonstrate the determining influence of changes in living conditions on the population risk of NIDDM.

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

BackgroundThe 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.MethodsUsing a standardized analysis strategy we examined prevalence estimates for 8 white and 3 black populations (N = 85,000 participants).ResultsThe range in hypertension prevalence was from 27 to 55% for whites and 14 to 44% for blacks.ConclusionsThese data demonstrate that not only is there a wide variation in hypertension prevalence among both racial groups, the rates among blacks are not unusually high when viewed internationally. These data suggest that the impact of environmental factors among both populations may have been under-appreciated.

ACE, angiotensinogen and obesity: a potential pathway leading to hypertension.

The renin-angiotensin system (RAS) plays a crucial role in the regulation of fluid volume, thereby influencing blood pressure (BP). Obesity is an important risk factor for hypertension, however the physiologic basis for this relationship has not been clarified. In a population survey we examined the potential relationship between the RAS and obesity. Based on community sampling, 449 individuals were recruited from metropolitan Kingston, Jamaica. Serum angiotensin-converting enzyme (ACE) and circulating angiotensinogen levels were measured and the associated genes were typed for previously described polymorphisms. Obese individuals (body mass index >31) had significantly higher serum ACE and angiotensinogen levels, this relationship persisted for ACE in multivariate analyses controlling for BP, hypertension status, age, and gender. The insertion/deletion polymorphism of the ACE gene was associated with variation in the levels of ACE, but inconsistently with body mass index. Variants of the angiotensinogen gene leading to amino acid substitutions at positions 174 and 235 did not influence levels either of angiotensinogen or obesity. These data suggest that obesity may alter the levels of ACE and angiotensinogen, and provide a potential pathway through which obesity leads to elevation of BP.

Fetal growth is directly related to maternal anthropometry and placental volume

Objective: To describe the influence of maternal weight and weight gain, placental volume and the rate of placental growth in early pregnancy on fetal dimensions measured sonographically.Design: In a prospective study, 712 women were recruited from the antenatal clinic of the University Hospital of the West Indies. Data analysis was confined to 374 women on whom measurements of the placental volume at 14, 17 and 20 weeks gestation were complete. Measurements of maternal anthropometry and fetal size (by ultrasound) were performed. Weight gain in pregnancy between the first antenatal visit (8–10 weeks) and 20 weeks gestation, and the rate of growth of the placenta between 14–17 and 17–20 weeks gestation were calculated.Main outcome measures: Fetal anthropometry (abdominal and head circumferences, femoral length, and biparietal diameter) at 35 weeks gestation.Results: Lower maternal weight at the first antenatal visit was associated with a significantly smaller placental volume at 17 and 20 weeks gestation (P<0.002 and <0.0001 respectively). In all women, maternal weight gain was directly related to fetal anthropometry. Placental volume at 14 weeks gestation and the rate of growth of the placenta between 17 and 20 weeks gestation were significantly related to all four fetal measurements.Conclusion: This study has provided evidence that both placental volume, and the rate of placental growth may influence fetal size. These effects are evident in the first half of pregnancy, and appear to be mediated through maternal weight and weight gain.Sponsorship: This study was supported by a grant from the Wellcome Trust, 183 Euston Road, London, England.