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Biomedical subjects

C N Rotimi

Publications and source records attributed to C N Rotimi.

At least 19 recordsLinked to original sources
PubMed2005

Beta cell function and response to treatment in Nigerians with Type 2 diabetes mellitus.

There are scant data from African populations on the association between beta-cell function and response to treatment with oral hypoglycaemic agents in Type 2 diabetes mellitus (T2DM). Fasting plasma C-peptide (FCP) and glucagon-stimulated C-peptide (GSCP) levels were measured in 116 Nigerians with T2DM at a university teaching hospital. After 9 months of follow-up and treatment, they were categorized into three groups based on response to treatment: (A) good control but not on maximum sulphonylurea (SU) therapy, (B) inadequate control but not on maximum SU therapy and (C) on maximum SU therapy+/-insulin or biguanide. Logistic regression models were used to investigate how well C-peptide levels predicted the subjects belonging to Group C who are likely to require insulin. The mean FCP and mean GSCP levels of Group C were significantly lower than in the other groups (p=0.024; p= <0.001 respectively). A GSCP cut-off value of < or =1.3 ng/mL predicted membership of Group C with 85% sensitivity and 89% specificity while a cut-off of < or =1.8 ng/mL was associated with 91% sensitivity and 66% specificity. In resource-poor settings where inadequate treatment are common, estimation of GSCP may be useful in predicting treatment response and should be weighed against the cost of inadequate therapy with higher morbidity and mortality.

Blood Glucose↗
PubMed2004

Conceptualizing human variation.

What is the relationship between the patterns of biological and sociocultural variation in extant humans? Is this relationship accurately described, or best explained, by the term 'race' and the schema of 'racial' classification? What is the relationship between 'race', genetics and the demographic groups of society? Can extant humans be categorized into units that can scientifically be called 'races'? These questions underlie the discussions that address the explanations for the observed differences in many domains between named demographic groups across societies. These domains include disease incidence and prevalence and other variables studied by biologists and social scientists. Here, we offer a perspective on understanding human variation by exploring the meaning and use of the term 'race' and its relationship to a range of data. The quest is for a more useful approach with which to understand human biological variation, one that may provide better research designs and inform public policy.

Demography↗
PubMed2001

Distribution and functional consequences of nucleotide polymorphisms in the 3'-untranslated region of the human Sep15 gene.

Selenium has been shown to prevent cancer in a variety of animal model systems. Both epidemiological studies and supplementation trials have supported its efficacy in humans. However, the mechanism by which selenium suppresses tumor development remains unknown. Selenium is present in known human selenoproteins as the amino acid selenocysteine (Sec). Sec is inserted cotranslationally in response to UGA codons within selenoprotein mRNAs in a process requiring a sequence within the 3'-untranslated region (UTR), referred to as a Sec insertion sequence (SECIS) element. Recently, a human Mr 15,000 selenoprotein (Sep15) was identified that contains an in-frame UGA codon and a SECIS element in the 3'-UTR. Examination of the available cDNA sequences for this protein revealed two polymorphisms located at position 811 (C/T) and at position 1125 (G/A) located within the 3'-UTR. Here, we demonstrate significant differences in Sep15 allele frequencies by ethnicity and that the identity of the nucleotides at the polymorphic sites influences SECIS function in a selenium-dependent manner. This, together with genetic data indicating loss of heterozygosity at the Sep15 locus in certain human tumor types, suggests that Sep15 may be involved in cancer development, risk, or both.

3' Untranslated Regions↗
PubMed2001

In search of susceptibility genes for type 2 diabetes in West Africa: the design and results of the first phase of the AADM study.

PURPOSE: The purpose of this study is to map type 2 diabetes susceptibility genes in West African ancestral populations of African-Americans, through an international collaboration between West African and US investigators. DESIGN AND METHODS: Affected sib-pairs (ASP) along with unaffected spouse controls are being enrolled and examined in West Africa, with two sites established in Ghana (Accra and Kumasi) and three in Nigeria (Enugu, Ibadan, and Lagos). Eligible participants are invited to study clinics to obtain detailed epidemiologic, family, and medical history information. Blood samples are drawn from each participant to measure glucose, insulin, C-peptide, total cholesterol, LDL, HDL, triglycerides, albumin, creatinine, urea, uric acid, total calcium and to detect autoantibodies to glutamic acid decarboxylase (GAD). DNA is isolated from frozen white blood cells obtained from 20 ml of EDTA whole blood samples. RESULTS: With full informed consent, 162 individuals from 78 families have been enrolled and examined since the Africa America Diabetes Mellitus (AADM) study began in June of 1997. Logistics of field examinations and specimen shipping have been successfully established. At the end of the third year of field activity (September 2000) the AADM study will have enrolled and performed comprehensive examination on 400 ASP with type 2 diabetes, for a minimum of 800 cases and 200 controls from Ghana and Nigeria. At the current participation rate, the goal of 400 sib-pairs and 200 controls will be met before the scheduled closing date. CONCLUSIONS: The AADM study will create a comprehensive epidemiologic and genetic resource that will facilitate a powerful genome-wide search for West African susceptibility genes to type 2 diabetes.

Africa, Western↗
PubMed2001

The beta 3-adrenergic receptor gene and obesity in a population sample of African Americans.

OBJECTIVE: To examine the role of the Trp64Arg polymorphism in the beta 3-adrenergic receptor gene and the beta 3-adrenergic receptor gene locus in obesity-related traits in African Americans. SUBJECTS: A total of 687 individuals representing 193 African American families who were residents of metropolitan Chicago. MEASUREMENTS: Genotyping of the Trp64Arg polymorphism in the beta 3-adrenergic receptor gene and three microsatellite markers flanking the beta 3-adrenergic receptor gene (ADRB3) locus and measuring various obesity-related traits, including body mass index (BMI), fat-free mass, fat mass, percentage fat mass, waist circumference and serum lipid levels. RESULTS: The prevalence of obesity (defined as body mass index > or = 30 kg/m(2)) in the population was 27.3% and 51.2% in men and women, respectively. The frequency of the Arg64 allele was 10.0%. Multivariate regression analyses confirmed the existence of a significant contribution of familial variance to each of the five obesity-related traits noted above. Likelihood ratio statistics computed in a multivariate regression analysis failed to demonstrate a significant association between the Arg64 allele and any of the five obesity-related traits. Single and multipoint analyses using extended Haseman--Elston regression analyses failed to demonstrate suggestive evidence of linkage of three microsatellite markers that flank the beta 3-adrenergic receptor gene to BMI, percentage body fat, waist circumference or serum leptin levels. CONCLUSION: Given the contribution of familial variance to obesity-related traits in this population, neither the null finding for the Arg64 allele nor the lack of evidence of linkage of the ADRB3 locus to obesity-related traits could be attributed to lack of transmissibility of the traits suggesting that neither the Arg64 variant of the beta 3-adrenergic receptor gene nor another genetic variant in or near the ADRB3 locus contribute significantly to familial aggregation of obesity-related traits in African Americans. International Journal of Obesity (2001) 25, 54-60

Adipose Tissue↗
PubMed2001

Heritability of obesity-related traits among Nigerians, Jamaicans and US black people.

OBJECTIVE: The mean values for anthropometric traits vary across population groups and this variation is clearly determined for the most part by the environment. The familiarity of anthropometric traits also varies in reports from different populations, although this variation has not been shown to follow a consistent pattern. To examine whether heritability is influenced by socio-cultural factors, we conducted a cross-cultural study of populations of the African diaspora. PARTICIPANTS: Data were collected on 1868 family members from Nigeria, 623 from Jamaica and 2132 from metropolitan Chicago, IL, USA. MEASUREMENTS: Height and weight were measured and body mass index (kg/m(2)) calculated. Fat-free mass, fat mass and percentage body fat were estimated using bioelectrical impedance analysis. Plasma leptin concentrations were also measured. The proportion of variance attributable to additive genetic and non-shared environmental components was estimated with the maximum likelihood variance decomposition method. RESULTS: Mean values for all anthropometric traits increased along the socio-cultural gradient, and obesity increased from 5% in Nigeria to 23% in Jamaica and 39% in the USA. Within populations the relationships among traits both within individuals and within families were highly consistent. Heritability estimates for weight, body mass index, fat mass and percentage body fat were approximately 50% for all groups. Heritability for height was lower in Nigeria (62%) than in Jamaica (74%) or the US (87%). CONCLUSION: The familial patterns of body size and energy storage appear to be consistent in these genetically related populations across a wide range of environmental conditions.

Adult↗
PubMed2000

Predictive values of waist circumference for dyslipidemia, type 2 diabetes and hypertension in overweight White, Black, and Hispanic American adults.

Waist circumferences (WC) >/=102 cm for men and >/=88 cm for women have been proposed by an expert panel as cut-points for identifying increased risk for the development of obesity comorbidities for most adults. The aim of this investigation was to examine the predictive values of these WC cut-points for hypercholesterolemia, low concentration of high (HDL-C), and high concentration of low (LDL-C) density lipoprotein cholesterol, hypertriglyceridemia, type 2 diabetes, and hypertension in overweight American adults. Data from NHANES III were utilized for the analysis. Predictive abilities were determined by calculating sensitivity, specificity, positive (PV+) and negative (PV-) predictive values in overweight subjects with BMI 25-29.9 kg/m(2). Sensitivity of WC cut-point was stronger for high LDL-C compared to other risk factors with the highest values recorded in the 40-59 and 60-69 year age groups in men and women, respectively. PV+ of WC cut-points for dyslipidemia, type 2 diabetes, and hypertension were low in men compared to women. PV+ tended to increase with age, from 19-39, 40-59 to 60-90 year age groups in Whites, Blacks, and Hispanic men. In men, the highest PV+ were recorded for hypertriglyceridemia in the 60-90 years old groups, with values of 71.6%, 52.5%, and 43.3% in Whites, Blacks, and Hispanics, respectively. The CVD risk factor associated with the highest PV+ in women was diabetes with values of 97.2% in Whites and 88.9% in Blacks, and hypertriglyceridemia with a value of 93.8% in the 17-39 year age group in Hispanics. Among Black men 40-59 years of age, only 32% of a population of overweight hypertensives were detected by the WC cut-points, and among Black women, 40-59 years of age, only 54% were detected. Given the low sensitivity of these cut-points for detecting hypertension, one of the major co-morbidities of obesity, these cut-points failed to provide adequate evidence for the use of WC in determining or evaluating patients as to co-morbid states. We recommend further studies to determine a set of specific cut-points associated with increased risk of CVD in different population groups.

Adolescent↗
PubMed2000

Lack of association between a biallelic polymorphism in the adducin gene and blood pressure in whites and African Americans.

Population-based candidate gene association analyses are becoming increasingly popular as a result of a greater number of genes and gene polymorphisms having been identified for which some functional information is available. Because many biochemical and physiologic systems impact blood pressure regulation and hypertension susceptibility, many of these identified genes and polymorphisms are candidates for population-level association studies involving blood pressure levels or hypertension status. Recent studies have suggested that the alpha-adducin gene may harbor polymorphisms that influence blood pressure level. Therefore, we embarked on a study to test one such polymorphism in two large US samples: one from an urban African American population (Maywood, IL) and another from a rural white population (Tecumseh, MI). We used both family-based association tests and tests that consider the impact of additional measured factors beyond adducin gene variation on blood pressure levels. We found no evidence for a significant effect of the chosen adducin polymorphism on blood pressure variation in either sample. We also found no association between Adducin genotypes and antihypertensive use. These facts, together with similar findings in companion studies, suggest that the alpha-adducin gene polymorphism does not have a pronounced effect on blood pressure variation in the populations studied. This does not suggest, however, that the alpha-adducin gene does not have a role in blood pressure regulation and hypertension susceptibility.

Adult↗
PubMed2000

Abdominal adiposity and clustering of multiple metabolic syndrome in White, Black and Hispanic americans.

PURPOSE: The aim of this study was to evaluate the association of abdominal adiposity assessed by waist circumference (WC) with clustering of multiple metabolic syndromes (MMS) in White, Black and Hispanic Americans. MMS was defined as the occurrence of two or more of either hypertension, type 2 diabetes mellitus, dyslipidemia, hypertriglyceridemia or hyperinsulinemia. METHODS: The number of MMS and fasting insulin (a surrogate measure of MMS) were each used as dependent variables in gender-specific multiple linear regression models, adjusting for age, smoking and alcohol intake. The contribution of WC to interethnic differences in clustering of MMS and fasting insulin concentration was assessed in gender-specific linear regression models. The risk of MMS due to large waist was estimated by comparing odds ratio for men with WC >/= 102 cm with those with WC < 102, and women with WC >/= 88 cm with women with WC < 88 cm in the logistic regression model adjusting for age, smoking and alcohol intake. RESULTS: WC was positively and independently associated with clustering of MMS and increased fasting insulin concentration adjusting for age, smoking and alcohol intake in the three ethnic groups (p < 0.01). Black ethnicity was associated with clustering of MMS and fasting insulin concentration (p < 0.01). Hispanic ethnicity was also associated with clustering of MMS in men and associated with fasting insulin concentration in both men and women (p < 0.01). In both men and women, the risk of MMS clustering was strongly associated with increased WC in all ethnic groups independent of BMI. CONCLUSION: WC appears to be a marker for multiple metabolic syndromes in these ethnic groups. The results of this investigation lend support to the view that waist measurement should be considered as a clinical variable for assessing the risk of cardiovascular diseases.

Abdomen↗
PubMed2000

Comparability of resting energy expenditure in Nigerians and U.S. blacks.

OBJECTIVE: To determine the influence of environmental factors on resting energy expenditure (REE) and its relationship to adiposity in two populations of West African origin, Nigerians and U.S. blacks. RESEARCH METHODS AND PROCEDURES: REE and body composition were measured in a cross-sectional sample of 89 Nigerian adults (39 women and 50 men), and 181 U.S. black adults (117 women and 65 men). Both groups represent randomly selected population samples. REE was measured by indirect calorimetry after an overnight fast in both sites using the same instrument. Body composition was estimated using bioelectrical impedance analysis (BIA) in 72 Nigerians and 156 U.S. participants. Multivariate regression analysis was used to determine the significant predictors of REE. The analyses were repeated in a set of 17 Nigerians and 28 U.S. blacks in whom body composition was measured using deuterium dilution. RESULTS: U.S. black adults were significantly heavier and had both more fat-free mass (FFM) and body fat than Nigerians. FFM was the only significant determinant of REE in both population groups, whether body composition was measured using BIA or deuterium dilution. The relationship between REE and body composition did not differ by site. There was no relationship between REE and adiposity. DISCUSSION: Differences in current environmental settings did not impact REE. The differences observed in mean levels of body fat between Nigerians and U.S. blacks were not the result of differences in REE adjusted for body composition.

Adipose Tissue↗
PubMed2000

Predictive value of abdominal obesity cut-off points for hypertension in blacks from west African and Caribbean island nations.

BACKGROUND: Waist circumferences (WC) >/=94 cm for men and >/=80 cm for women (action level I) and >/=102 cm for men and >/=88 cm for women (action level II) have been suggested as limits for health promotion purposes to alert the general public to the need for weight loss. In this analysis we examined the ability of the above cut-off points to correctly identify subjects with or without hypertension in Nigeria, Cameroon, Jamaica, St Lucia and Barbados. We also determined population- and gender-specific abdominal adiposity cut-off points for epidemiological identification of risk of hypertension. METHODS: Waist measurement was made at the narrowest part of the torso as seen from the front or at midpoint between the bottom of the rib cage and 2 cm above the top of the iliac crest. Sensitivity and specificity of the established WC cut-off points for hypertension were compared across sites. With receiver operating characteristics (ROC), population- and gender-specific cut-off points associated with risk of hypertension were determined over the entire range of WC values. RESULTS: Predictive abilities of the established WC cut-off points for hypertension were poor compared to the specific cut-off points estimated for each population. Different values of WC were associated with increased risk of hypertension in these populations. In men, WC cut-off points of 76, 81, 80, 83 and 87 cm provided the highest sensitivity for identifying hypertensives in Nigeria, Cameroon, Jamaica, St Lucia and Barbados, respectively. The analogous cut-off points in women were 72, 82, 85, 86 and 88 cm. CONCLUSIONS: The waist cut-off points from this study represent values for epidemiological identification of risk of hypertension. For the purpose of health promotion, the decision on what cut-off points to use must be made by considering other additional factors including overall impact on health due to intervention (e.g. weight reduction) and potential burden on health services if a low cut-off point is employed. There is a need to develop abdominal adiposity cut-off points associated with increased risks for cardiovascular diseases in different societies, especially for those populations where the distribution of obesity and associated risk factors tends to be very different from those of the technologically advanced nations. International Journal of Obesity (2000) 24, 180-186

Abdomen↗
PubMed2000

Impact of birth weight on ethnic variations in subcutaneous and central adiposity in American children aged 5-11 years. A study from the Third National Health and Nutrition Examination Survey.

OBJECTIVE: To determine the types of subcutaneous adiposity represented by different measurements of skinfold thickness that are associated with birth weight in white (n=759), Black (n=916) and Hispanic (n=813) American children aged 5-11 y. We also determined the contribution of birth weight to ethnic differences in subcutaneous and central adiposity. DESIGN AND METHODS: Data for this analysis were from the Third US National Health and Nutrition Examination Survey. The outcome measures were triceps, subscapular, suprailiac and thigh skinfold thicknesses at 5-11 y of age. Central adiposity was defined as ratios of subscapular to triceps (STR) and central-peripheral (CPR) (subscapular+suprailiac)/(triceps+thigh) skinfolds. Partial correlation analyses were used to determine the association between birth weight and measures of subcutaneous fatness, while multiple linear regression analyses were used to determine the independent contribution of birth weight to ethnicity variations in subcutaneous and central adiposity adjusting for sex, age and BMI. RESULTS: Overall, birth weight was negatively associated with subscapular skinfold and central adiposity in White, Black and Hispanic American children (P < 0.05). Birth weight was also negatively associated with suprailliac skinfold in both Blacks and Hispanics (P < 0.01) and with sum of the four skinfolds in Blacks (P < 0.05). Compared with White, Black ethnicity was negatively associated with triceps, suprailliac thigh and sum of skinfold thicknesses controlling for birth weight, sex, age and BMI (P < 0.01). Compared with White, Hispanic ethnicity was negatively associated with triceps, thigh and sum of skinfold thicknesses (P < 0.01). Both Black and Hispanic ethnicity was positively associated with STR and CPR (P < 0.01). CONCLUSIONS: In this population of American children, the association of birth weights with subcutaneous and central fat accumulation may be due to fetal programming. Since the impact of fetal conditions is likely to be modified by life course, defining the interaction between factors that are present at birth and subsequent exposures is one of the essential challenges for future research.

Adipose Tissue↗
PubMed2000

Heritability of angiotensin-converting enzyme and angiotensinogen: A comparison of US blacks and Nigerians.

Angiotensinogen (AGT) and angiotensin I-converting enzyme (ACE) are heritable traits, but whether the environmental context influences heritability has not been examined. Known genetic factors explain only a portion of variation in AGT and ACE, and levels of both proteins are influenced by the environment. The African diaspora provides an opportunity to compare these traits in genetically related populations in contrasting environments. As part of a study of the genetics of hypertension, we examined families that included 1449 Nigerians and 1147 African Americans. Body mass index (weight [kg]/height [m](2)) was 21 kg/m(2) in Nigeria and 29 kg/m(2) in the United States, which is consistent with a large environmental contrast. AGT was considerably higher among African Americans (1919 versus 1396, P<0.01), whereas ACE was higher in Nigerians (630 versus 517, P<0.01). A household effect was observed among the Nigerian families (spouse correlations 0.30 for AGT, 0.18 for ACE), and correlations among first-degree relatives were large (0.42 to 0. 51 and 0.36 to 0.38 for AGT and ACE, respectively). Among African Americans, the familial aggregations of AGT and ACE were very limited, and the familial correlation for AGT was not different from zero. Heritability was 77% for AGT and 67% for ACE in Nigeria and 18% for AGT and ACE in the United States. The familial patterns of body mass index and blood pressure were similar among both family sets. In conclusion, less familial aggregation was observed for AGT and ACE in the United States than in Nigeria, most likely reflecting a greater random individual environmental effect on these traits. Variation in heritability of traits could influence the power of epidemiological studies to identify genetic effects.

Adult↗
PubMed1999

Abdominal adiposity in six populations of West African descent: prevalence and population attributable fraction of hypertension.

OBJECTIVES: The objective of this investigation was to examine the prevalence of abdominal adiposity and its association with the prevalence of hypertension among African descent populations in Nigeria, Cameroon, Jamaica, St. Lucia, Barbados, and the United States (US). RESEARCH METHOD: The data for this investigation were obtained from the International Collaborative Study on Hypertension in Blacks. Hypertension was defined as mean diastolic blood pressure > or =90 mmHg, systolic blood pressure > or = 140 mmHg or current treatment with prescribed anti-hypertension medication. Abdominal overweight was defined as waist circumference (WC) > or =94 and > or =80 cm for men and women, respectively. Abdominal obesity was defined as WC > or =102 and > or =88 cm for men and women, respectively. We estimated the site-specific prevalence of abdominal overweight and obesity across age and body mass index cut-points. We also calculated the population attributable fraction (AF) of hypertension due to abdominal adiposity. RESULTS: The prevalence of hypertension in these populations was tightly linked to abdominal adiposity. Increases in abdominal overweight accompanied an increasing degree of Westernization, rising from 6.4% and 26.3% in Nigeria, 16.5% and 62.8% in Cameroon, 15.8% and 58.6% in Jamaica, 14.3% and 62.1% in St. Lucia, 21.4% and 70.3% in Barbados to 38.9%, and 76.4% in the US for men and women, respectively. The corresponding values for abdominal obesity were 1.6% and 12.3% in Nigeria, 5.1% and 38.9% in Cameroon, 5.5% and 34.0% in Jamaica, 2.7% and 40.7% in St. Lucia, 7.8% and 44.7% in Barbados to 21.7% and 54.1% in the US for men and women, respectively. Body mass index-adjusted estimates of AF suggest that in most of these populations, especially in females, avoidance of abdominal overweight or obesity would help to curb the development of hypertension. DISCUSSION: An important public health challenge is to clarify how lifestyle factors influence risks of abdominal adiposity and ultimately the increased risk of cardiovascular diseases.

Abdomen↗
PubMed1999

Maximum-likelihood generalized heritability estimate for blood pressure in Nigerian families.

Elevated blood pressure (BP) is more common in relatives of hypertensives than in relatives of normotensives, indicating familial resemblance of the BP phenotypes. Most published studies have been conducted in westernized societies. To assess the ability to generalize these estimates, we examined familial patterns of BP in a population-based sample of 510 nuclear families, including 1552 individuals (320 fathers, 370 mothers, 475 sons, and 387 daughters) from Ibadan, Nigeria. The prevalence of obesity in this community is low (body mass index: fathers, 21.6; mothers, 23.6; sons, 19.2; and daughters=21.0 kg/m2). The BP phenotype used in all analyses was created from the best regression model by standardizing the age-adjusted systolic blood pressure (SBP) and diastolic blood pressure (DBP) to 0 mean and unit variance. Heritability was estimated by use of the computer program SEGPATH from the most parsimonious model of "no spouse and neither gender nor generation difference" as 45% for SBP and 43% for DBP. The lack of a significant spouse correlation is consistent with little or no influence of the common familial environment. However, the heritability estimate of <50% for both SBP and DBPs reinforces the importance of the nonshared environmental effect.

Adult↗
PubMed1999

Blood pressure change in Africa: case study from Nigeria.

Studies of migrants and comparisons of rural versus urban communities are potentially informative study designs because they allow examination of genetically similar population subgroups exposed to diverse environmental conditions. These designs have been underused in Africa, where recent urbanization has created many situations in which nearby communities of common ethnicity and culture live under different social and economic circumstances. The International Study of Hypertension in Blacks (ICSHIB) conducted several overlapping surveys in Nigeria starting in 1993. These surveys were based primarily in the rural village of Idere and the urban community of Idikan, both inhabited by people defined ethnically as Oyo Yoruba and sharing a common language and culture. Survey teams collected standardized blood pressure and anthropometric measurements, and some study participants provided 24-hr urine samples and questionnaire data on psychosocial stress and social integration. Rural and urban groups differed substantially in blood pressure and related characteristics. Age-adjusted prevalence of hypertension (blood pressure > or = 140/90 mm Hg) for participants aged 25 years and older was 7-8% in Idere and 24-27% in Idikan. The distributions of overweight, sodium/potassium ratio, perceived stress, and social integration scores all contributed to lower hypertension risk in Idere. The effects and interactions of these identified risk factors remain poorly understood, even among people who share a common genetic background, similar diet, and many other lifestyle features. Nonetheless, the rural-urban distinction is sufficiently salient to engender a nearly threefold difference in hypertension prevalence. This disparity in disease prevalence demonstrates the sensitivity of human beings to the environmental determinants of disease and provides a sobering example of the difficulty in identifying subtle genetic effects, which can be easily overwhelmed by small differences in environmental exposures.

Adult↗