Admixture and population stratification in African Caribbean populations.

Throughout biomedical research, there is growing interest in the use of ancestry informative markers (AIMs) to deconstruct racial categories into useful variables. Studies on recently admixed populations have shown significant population substructure due to differences in individual ancestry; however, few studies have examined Caribbean populations. Here we used a panel of 28 AIMs to examine the genetic ancestry of 298 individuals of African descent from the Caribbean islands of Jamaica, St. Thomas and Barbados. Differences in global admixture were observed, with Barbados having the highest level of West African ancestry (89.6%+/- 2.0) and the lowest levels of European (10.2%+/- 2.2) and Native American ancestry (0.2%+/- 2.0), while Jamaica possessed the highest levels of European (12.4%+/- 3.5) and Native American ancestry (3.2%+/- 3.1). St. Thomas, USVI had ancestry levels quite similar to African Americans in continental U.S. (86.8%+/- 2.2 West African, 10.6%+/- 2.3 European, and 2.6%+/- 2.1 Native American). Significant substructure was observed in the islands of Jamaica and St. Thomas but not Barbados (K=1), indicating that differences in population substructure exist across these three Caribbean islands. These differences likely stem from diverse colonial and historical experiences, and subsequent evolutionary processes. Most importantly, these differences may have significant ramifications for case-control studies of complex disease in Caribbean populations.

Nine-year incidence of obesity and overweight in an African-origin population.

OBJECTIVE: To provide 9-year incidence estimates for obesity and overweight and describe weight changes over time in an African-origin population. DESIGN: A population-based cohort in which participants were examined at baseline and reexamined after 9 years. MEASUREMENTS: Obesity and overweight were defined as having body mass indices (BMIs)> or =30 and 25 kg m(-2), respectively. Incidence rates were based on persons without such conditions at baseline and are presented along with 95% confidence intervals. RESULTS: Of the 869 men and 921 women at risk at baseline, the 9-year gender-specific incidence rates for obesity were 6.9% (95% confidence interval (5.3, 8.8)) and 13.1% (11.0, 15.5), respectively. The incidence of obesity steadily declined with age, decreasing from 14.4% for those between 40 and 49 years of age to 1.5% for those who were 70 years and older. Overall, the incidence of obesity over 9 years was approximately 10%. The 9-year incidence rate for overweight was 23.3% (20.5, 26.3). Changes in weight over the 9-year period varied by age group. Persons 40-49 years of age at baseline gained, on average, almost 3% of their baseline body weight, whereas persons > or =70 years lost 5% of their body weight in 9 years. CONCLUSIONS: This study highlights the high incidence of obesity/overweight in this cohort and suggests that the future public health burden of excess weight and its associated comorbidities may be elevated in this population of African origin. The development of strategies and interventions for the prevention and treatment of obesity/overweight are therefore of primary and immediate importance.

Incident open-angle glaucoma and intraocular pressure.

PURPOSE: To evaluate the role of baseline intraocular pressure (b-IOP) as a risk factor for incident open-angle glaucoma (OAG) in participants of African origin from the Barbados Eye Studies. DESIGN: Population-based 9-year cohort study. PARTICIPANTS: Three thousand two hundred twenty-two persons examined during the study period who were free of glaucoma at baseline and at risk of developing OAG during the 9-year follow-up. METHODS: Study protocols were standardized and included ophthalmic and other measurements, automated perimetry, applanation tonometry, fundus photography, and comprehensive ophthalmologic examination for those referred. The product-limit approach was used to estimate incidence. Relationships between b-IOP and incidence were evaluated by adjusted relative risk ratios (RRs) with 95% confidence intervals (CIs), based on Cox regression models. MAIN OUTCOME MEASURE: The 9-year incidence of OAG was based on both visual field and optic disc abnormalities, with ophthalmologic evaluations to exclude other possible causes. RESULTS: The overall 9-year incidence of OAG was 4.4% (95% CI, 3.7%-5.2%), and the mean (standard deviation) b-IOP among persons at risk was 18.0 mmHg (4.1). Among the 125 incident OAG cases, the mean b-IOP was 21.9 mmHg and 46% had b-IOP of >21 mmHg. In contrast, the nonincident group had a mean b-IOP of 17.8 mmHg and only 12% had b-IOP of >21 mmHg. Overall, OAG risk increased by 12% with each 1-mmHg increase in IOP (RR, 1.12; 95% CI, 1.08-1.16). Incidence steadily increased from 1.8% (95% CI, 1.2%-2.7%) for persons with b-IOP of < or =17 mmHg (referent group) to 22.3% (95% CI, 15.8%-31.1%) for those with b-IOP > 25 mmHg, resulting in an adjusted RR of 13.1 (95% CI, 7.1-24.1) among the latter group. The attributable risk for IOP of >25 mmHg was 19%. Using 21 mmHg as a cutoff, the RR was 7.9 (95% CI, 3.8-16.2) and the attributable risk was 37%. CONCLUSIONS: After 9 years' follow-up, the risk of OAG was positively related to IOP levels at baseline. Although persons with b-IOP of >25 mmHg had a 13-fold RR of developing OAG, most cases arose with lower b-IOP. This study thus confirms the role of IOP as an influential risk factor, yet at the same time underscores its limitations in predicting OAG.

Nine-year incidence of open-angle glaucoma in the Barbados Eye Studies.

PURPOSE: To determine the 9-year incidence of open-angle glaucoma (OAG) in African-descent participants of the Barbados Eye Studies. DESIGN: Nine-year cohort study with 81% to 85% participation. PARTICIPANTS: Three thousand two hundred twenty-two persons without definite OAG at baseline, at risk of developing OAG at follow-up. METHODS: The standardized protocol included automated perimetry and various ophthalmic measurements, with a comprehensive ophthalmologic examination for those referred. Fundus photographs were evaluated independently by masked graders. Incidence was estimated by the product-limit approach. Relative risk (RR) ratios with 95% confidence intervals (CIs) were based on Cox regression models with discrete time. MAIN OUTCOME MEASURE: Nine-year incidence of definite OAG, based on the development of visual field defects and glaucomatous optic neuropathy, with ophthalmologic confirmation. RESULTS: The 9-year incidence of definite OAG was 4.4% (95% CI, 3.7%-5.2%), or an average of 0.5%/year, based on 125 new cases. Incidence increased greatly with age, from 2.2% at ages 40 to 49 years to 7.9% at ages 70 years or older, and tended to be higher in men than women (4.9% vs. 4.1%; RR, 1.3; 95% CI, 0.9-1.8). More than half (53%) of new cases were undetected, and of these, one third had intraocular pressure of 21 mmHg or less. When 141 persons developing suspected/probable OAG were considered, the total incidence was 9.4% (8.4%-10.6%), averaging approximately 1%/year, also increasing with age, and significantly higher in men than women (10.7% vs. 8.6%; RR, 1.31; 95% CI, 1.02-1.67). CONCLUSIONS: These new data provide a measure of the long-term risk of OAG in an African-descent population, which is markedly higher than in persons of European ancestry. Results confirm the increased risk with age and in men. The incidence data fill a gap in our understanding of OAG risk and have implications for public health policy and planning; they also will allow the study of factors related to the risk of OAG development.

Frequency and risk factors for pterygium in the Barbados Eye Study.

OBJECTIVE: To describe the distribution and risk factors for pterygium in the predominantly black population of the Barbados Eye Study, which was based on a random sample of Barbadian-born citizens between the ages of 40 and 84 years. METHODS: The standardized protocol included ophthalmic and other measurements, automated perimetry, lens gradings, fundus photography, and a detailed interview. A 10% systematic sample of participants and those meeting specific criteria also received a comprehensive ophthalmologic evaluation. RESULTS: The Barbados Eye Study included 4709 participants, of whom 2978 were referred for an ophthalmologic evaluation and 2781 (93%) completed the examination. Cases of pterygium were found among 23.4% of 2617 black, 23.7% of 97 mixed (black and white), and 10.2% of 59 white participants examined. In addition to African ancestry, logistic regression analyses indicated a positive association between pterygium and age (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.00-1.02), fewer years of education (OR, 1.43; 95% CI, 1.01-2.03), and an outdoor job location (OR, 1.87; 95% CI, 1.52-2.29). Having a darker skin complexion (OR, 0.66; 95% CI, 0.52-0.83), always using sunglasses outdoors (OR, 0.18; 95% CI, 0.06-0.59), and the use of prescription glasses (OR, 0.75; 95% CI, 0.60-0.93) were protective factors. CONCLUSIONS: Approximately one quarter of the black participants examined had pterygia, a frequency that was 2.5 to 3 times higher than among whites in the Barbados Eye Study and elsewhere. Pterygium was almost twice as frequent among persons who worked outdoors but was only one fifth as likely among those who always used sunglasses outdoors. Educational interventions to modify these potential exposures may assist in preventing pterygium.

Prevalence and causes of visual impairment in The Barbados Eye Study.

OBJECTIVE: To determine the prevalence and causes of low vision and blindness in a predominantly black population. DESIGN: Population-based prevalence study of a simple random sample of Barbados-born citizens aged 40 to 84 years. PARTICIPANTS: Four thousand seven hundred nine persons (84% participation). METHODS: The standardized protocol included best-corrected visual acuity (with a Ferris-Bailey chart), automated perimetry, lens gradings (LOCS II), and an interview. Participants with visual acuity of worse than 20/30, other positive findings, and a 10% sample also had an ophthalmologic examination that evaluated the cause and extent of vision loss (resulting from that cause), if any. MAIN OUTCOME MEASURES: Low vision and blindness were defined as visual acuity in the better eye between 6/18 and 6/120 and visual acuity worse than 6/120, respectively (World Health Organization [WHO] criteria). RESULTS: Of the 4631 participants with complete examinations, 4314 (93%) reported their race as black, 184 (4%) reported their race as mixed (black and white), and 133 (3%) reported their race as white or other. Low vision was found in 5.9% of the black, 2.7% of the mixed, and 3.0% of white or other participants. Bilateral blindness was similar for black and mixed race participants (1.7% and 1.6%, respectively) and was not found in whites. Among black and mixed participants, the prevalence of low vision increased with age (from 0.3% at 40-49 years to 26.8% at 80 years or older). The prevalence of blindness was higher (P < 0.001) for men than women at each age group (0.5% versus 0.3% at ages 40-49 and 10.9% versus 7.3% at 80 years or more). Sixty percent of blindness was due to open-angle glaucoma and age-related cataract, each accounting for more than one fourth of cases. Other major causes were optic atrophy or neuropathy and macular and other retinal diseases. Few cases of blindness were due to diabetic retinopathy (1.4%), and none were due to age-related macular degeneration. CONCLUSIONS: Using the WHO criteria, prevalence of visual impairment was high in this African-origin population, particularly at older ages. Most blindness was due to open-angle glaucoma and cataract, with open-angle glaucoma causing a higher proportion of blindness than previously reported. The increased prevalence of blindness in men may be due to the increased male prevalence of glaucoma in this population and warrants further investigation. Results underline the need for blindness prevention programs, with emphasis on effective treatment of age-related cataract and enhancing strategies for early detection and treatment of open-angle glaucoma.

Inheritance of open-angle glaucoma in the Barbados family study.

The majority of genetic studies on open-angle glaucoma (OAG) have been conducted in primarily white populations, with investigations of inheritance patterns largely based on self-reported information. The Barbados Family Study of Open-Angle Glaucoma (BFSG) is the first study to investigate the transmission pattern(s) for OAG in a predominantly black population, based on standardized examinations. Each BFSG participant received a comprehensive examination including anthropometric and other measurements, best-corrected visual acuity, perimetry, tonometry, lens gradings, fundus photography, venipuncture, an extensive interview including ocular, medical and family history information and a comprehensive ophthalmologic evaluation. Conservative criteria were used to define glaucoma status, including the presence of both visual field defects and optic disc damage. The study included 207 OAG-affected probands (median age: 68 years) and 1,056 of their relatives (median age: 47 years). Among the relatives examined 10% (n = 106) had OAG and 13% (n = 141) had probable OAG. Segregation analyses were performed to determine the mode of inheritance for glaucoma in these families. The results indicate that transmission of OAG or probable OAG is most likely due to a major codominant gene. Both age and gender are shown to be significant factors as well; with an increase in risk being associated with each year of age over 54 years and an increase in risk for all ages and genotypes observed in males. These analyses do not, however, preclude the possible existence of an environmental component or other genetic determinants in OAG. Further evidence for the existence of a major gene may be obtained by additional follow-up of the relatively young cohort of relatives, as well as ongoing linkage analyses.

Patterns of open-angle glaucoma in the Barbados Family Study.

OBJECTIVE: To describe the Barbados Family Study of open-angle glaucoma (OAG) and present risk factors for OAG in siblings of study probands. DESIGN: Observational study of families of probands with OAG. PARTICIPANTS: Two hundred thirty probands and 1056 relatives (from 207 families). METHODS: Probands and their family members underwent standardized examinations, including automated perimetry, applanation tonometry, ophthalmologic evaluation, fundus photography, blood pressure, interview, and genotyping. Generalized estimation equation methods were used to evaluate risk factors. MAIN OUTCOME MEASURES: Presence of OAG in the relatives, as defined by both visual field and optic disc findings, after ophthalmologic exclusion of other causes. RESULTS: The median ages of probands and relatives were 68 and 47 years, respectively. In the 207 families, 29% of the probands had one relative with OAG and 10% had two or more relatives affected. Of the 1056 family members, 10% had OAG, 13% had suspect OAG, and 6% had ocular hypertension. One fifth of the 338 siblings had OAG (n = 67); they tended to be older and more often were male. Multivariate comparisons between siblings with and without OAG found that age, higher intraocular pressure (IOP), myopia, and lower diastolic blood pressure-IOP differences were related to OAG, whereas hypertension and diabetes were not. CONCLUSIONS: Based on standardized protocols and examinations, approximately one quarter of the relatives had OAG or suspected OAG, despite their relatively young age. Risk factors for OAG in siblings were similar to risk factors in unrelated individuals. Analyses are ongoing to determine OAG inheritance and to localize potential gene(s) involved.

Lens opacities and mortality : the Barbados Eye Studies.

OBJECTIVE: To evaluate the association between cataract and mortality in a black population by type of opacity, which has not been documented previously. DESIGN: Population-based cohort study. PARTICIPANTS: The Barbados Incidence Study of Eye Diseases reexamined the Barbados Eye Study cohort, identified through a simple random sample of predominantly black Barbadian-born citizens, aged 40 to 84 years. Of those eligible, 85% (3427 participants) had a 4-year follow-up visit. METHODS: Baseline and follow-up visits included an interview, blood pressure and other measurements, and a detailed ophthalmologic examination with slit-lamp lens gradings (Lens Opacities Classification System [LOCS] II protocol). Mortality at follow-up was verified from Ministry of Health records. MAIN OUTCOME MEASURES: Lens opacities were defined by a LOCS II score of 2 or more. Opacity types were classified in two ways: (1) single (cortical-only, nuclear-only, and posterior subcapsular-only) and mixed opacities; and (2) any cortical, any nuclear, or any posterior subcapsular opacities. Information on dates and causes of death was obtained from death certificates. RESULTS: Cardiovascular disease was the principal cause of death in black participants (3.6%), followed by malignant neoplasms (1.4%). The cumulative 4-year mortality varied with lens types, increasing from 3.2% for those without cataract to 6.0% for cortical-only, 8.8% for nuclear-only, and 20.9% for mixed opacities. Persons with mixed opacities had a 1.6-fold increase in mortality, while controlling for other factors (age, male gender, diabetes, hypertension, obesity, cigarette smoking, cardiovascular disease, and family history of diabetes) in Cox proportional-hazards regression analyses. Persons with any nuclear opacities also had increased mortality (death rate ratio, 1.5). The death rate ratios increased with age, but peaked at age 60 to 69 years. Coexisting diabetes further increased mortality: people with mixed opacities and diabetes had a 2.7-fold increased risk of death. A trend toward increased mortality from neoplasms was observed for individuals with mixed opacities or with any nuclear opacities. CONCLUSIONS: Participants with mixed opacities or any nuclear opacities had increased 4-year mortality rates, with diabetes acting as an effect modifier. This study is the first to identify a relationship between type of cataract and mortality in an African-descent population.

Incidence of open-angle glaucoma: the Barbados Eye Studies. The Barbados Eye Studies Group.

OBJECTIVE: To measure the 4-year risk of open-angle glaucoma (OAG) in a black population. DESIGN: Population-based cohort study with 4 years of follow-up. SETTING: Simple random sample of residents of Barbados, West Indies, aged 40 years or older. PARTICIPANTS: A total of 3427 members of the cohort (85% of those eligible). MAIN OUTCOME MEASURE: Development of glaucoma visual field defects and optic disc damage, confirmed by automated perimetry, independent fundus photographic gradings, and standardized ophthalmologic examinations. RESULTS: The 4-year risk of OAG in black participants was 2.2% (95% confidence interval, 1.7%-2.8%), based on 67 newly developed cases of OAG. Incidence rates increased from 1.2% at ages 40 to 49 years to 4.2% at ages of 70 years or more, tending to be higher in men than women (2.7% vs 1.9%). About half of the incident cases were undiagnosed previously, and the rest were receiving OAG treatment. Of the 67 new cases of OAG, 32 had intraocular pressure of 21 mm Hg or less at baseline (1.2% incidence) and 35 had higher pressures (9% incidence). Risk was highest among persons classified as having suspect OAG at baseline (26.1%), followed by those with ocular hypertension (4.9%) and lowest in the remaining population (0.8%). CONCLUSIONS: This longitudinal study provides new information on OAG risk, as well as the first incidence measurement in a black population. Although intraocular pressure increased risk, about half of the new cases had baseline pressures of 21 mm Hg or less. Results substantiate the high OAG risk in the population of African origin, especially in older adults; the relative role of intraocular pressure; and the considerable underdetection of new disease after 4 years of follow-up.

Observed versus indirect estimates of incidence of open-angle glaucoma.

Incidence data on open-angle glaucoma (OAG) are limited and difficult to obtain. To date, few studies have reported incidence directly measured from population-based cohorts. Other reported estimates have been derived indirectly from age-specific prevalence by using several assumptions, and their validity is unknown. To the authors' knowledge, this report presents the first comparison of observed versus indirect estimates of OAG incidence based on data from the population-based Barbados Incidence Study of Eye Diseases (1992-1997) (n = 3,427; 85% participation). The observed 4-year incidence of OAG was 1.2% (95% confidence interval (CI): 0.6, 2.1%) at ages 40-49 years, 1.5% (95% CI: 0.8, 2.5%) at ages 50-59 years, 3.2% (95% CI: 2.0, 4.8%) at ages 60-69 years, and 4.2% (95% CI: 2.6, 6.3%) in persons at ages 70 or more years. When incidence was calculated from the prevalence data, power function fitting achieved a closer approximation to observed incidence than did logistic curve fitting. Calculated incidence rates for each group were similar when assuming mortality that was equal (incidence rate = 0.7, 1.3, 2.3, and 4.8%) or differential (incidence rate = 0.7, 1.2, 2.4, and 4.8%). Other nonlogistic approaches also increased the resemblance of observed and calculated estimates. In the absence of longitudinal data, reasonably valid incidence estimates of OAG were obtained from available prevalence data. These estimation techniques can be useful when OAG incidence estimates are required for research or public health purposes.

Incidence and progression of lens opacities in the Barbados Eye Studies.

OBJECTIVE: To provide 4-year cumulative incidence and progression rates of age-related lens opacities in a population > or =40 years of age, which is mainly of African origin. DESIGN: Cohort study that reexamined surviving members of the population-based Barbados Eye Study 4 years after baseline. PARTICIPANTS: Three thousand four hundred twenty-seven members of the Barbados Eye Study cohort (85% of those eligible). MAIN OUTCOME MEASURES: The Lens Opacities Classification System II (LOCS II) was used at the slit lamp. Cumulative incidence was defined as the development of any nuclear, cortical or posterior subcapsular (PSC) opacities (LOCS II scores > or =2) among persons without that opacity type at baseline. Cumulative progression was defined by at least two-step increases in scores among persons with preexisting lens opacities. RESULTS: The incidence of cortical opacities was about five times greater in black than white participants (age-gender adjusted relative risk = 4.7; 95% confidence interval: 1.9-11.4). In the black population, the 4-year incidence rates were 22.2% (20.4%-24.0%) for any cortical, 9.2% (8.2%-10.4%) for any nuclear, and 3.3% (2.7%-4.0%) for any PSC opacities; rates increased greatly with age. Four-year progression rates were 12.5% for cortical, 3.6% for nuclear, and 23.0% for PSC opacities, without consistent pattern by age. Women had a greater risk of cortical and nuclear opacities (P<0.05) than men and greater progression of nuclear opacities. The presence of PSC opacities at baseline seemed to at least double the incidence and progression rates of other opacities. In persons initially opacity free, single cortical opacities were the predominant type to develop at followup. Visual acuity loss frequently accompanied incident opacities. CONCLUSIONS: This longitudinal study provides new population-based data on the natural history of lens opacities. Incidence and progression of opacities, especially of cortical opacities, were high. After 4 years of followup, 1 in 4 to 5 participants developed cortical opacities, 1 in 11 developed nuclear opacities, and 1 in 30 developed PSC opacities. The information obtained attests to the public health impact of age-related cataract, as well as its extent, in this and similar black populations.

Performance of the nonparametric linkage analysis using GENEHUNTER for a complicated genetic disease.

The nonparametric linkage (NPL) analysis of the GENEHUNTER program was applied to one set of the simulated data of Problem 2, GAW11. We conducted a straightforward screening of the genome to evaluate the performance of the NPL test, with respect to its ability to detect linkage on specific disease loci. Our findings indicate that disease genes were detected with relatively good power, despite the presence of a complex inheritance pattern. We found that the NPL test varies depending on penetrance rates and gene frequencies, however, we conclude that it is a useful tool for linkage analysis.

A normalized identity-by-state statistic for linkage analysis of sib pairs.

A sib-pair analysis was performed on a simulated data set for a fictitious disease, with a prevalence of approximately 3% to 6%. The disease could manifest itself in a severe or mild form and the analyses focused primarily on families with the mild form, barring any misdiagnoses. The numbers of shared genes identical by descent (IBD) and identical by state (IBS) were used to detect linkage between the marker loci and the disease. The results of the two methods were compared. We considered the distribution of the number of shared alleles IBS (for different parental allele combinations) and suggest a normalized IBS method. A large proportion of pedigrees in this data set had at least one homozygous parent or both parents sharing a common gene, thus generating the need for an adjustment of the IBS method. Our results indicate that the normalized IBS method gives results similar to those obtained by the traditional IBD approach. The adjusted score requires no assumptions be made with regard to the allele frequencies.

Refractive errors in a black adult population: the Barbados Eye Study.

PURPOSE: To describe the prevalence of refractive errors in a black adult population. METHODS: The Barbados Eye Study, a population-based study, included 4709 Barbados-born citizens, or 84% of a random sample, 40 to 84 years of age. Myopia and hyperopia were defined as a spherical equivalent <-0.5 diopters and >+0.5 diopters, respectively, based on automated refraction. Analyses included 4036 black participants without history of cataract surgery. Associations with myopia and hyperopia were evaluated in logistic regression analyses. RESULTS: The prevalence of myopia was 21.9% and was higher in men (25.0%) than in women (19.5%). The prevalence of hyperopia was 46.9% and was higher in women (51.8%) than in men (40.5%). The prevalence of myopia decreased from 17% in persons 40 to 49 years of age to 11% in those 50 to 59 years of age, but increased after 60 years of age. The prevalence of hyperopia increased from 29% at 40 to 49 years of age to 65% at 50 to 59 years of age, and tended to decline thereafter. A higher prevalence of myopia was positively associated (P < 0.05) with lifetime occupations requiring nearwork, nuclear opacities, posterior subcapsular opacities, glaucoma, and ocular hypertension. Factors associated with hyperopia were the same as for myopia, except for occupation, and in the opposite direction. CONCLUSIONS: High prevalences of myopia and hyperopia were found in this large black adult population. The prevalence of myopia (hyperopia) increased (decreased) after 60 years of age, which is inconsistent with data from other studies. The high prevalence of age-related cataract, glaucoma, and other eye conditions in the Barbados Eye Study population may contribute to the findings.

The power of iterated generalized least squares (GLS) method to detect direct relationships in the analysis of correlated quantitative traits.

We examined the power of the stepwise iterated generalized least squares (GLS) method by modeling the relationship between quantitative traits and other variables using the simulated data for Problem 2A. The comparison between the generating model provided by the workshop and the results of the stepwise iterated GLS model showed that this method could be used as a first step in identifying the underlying model for genetic data. The estimated covariance matrices also provide useful information about the genetic properties of the traits.

Analyses of reported family history of glaucoma: a preliminary investigation. The Barbados Eye Study Group.

This study investigated the self-reported family history of open-angle glaucoma (OAG) among 4,314 black participants in the Barbados Eye Study (BES), which was based on a random sample of Barbados-born citizens between 40 and 84 years of age. Data collection included Humphrey perimetry, fundus photography, various ophthalmic and other measurements and a comprehensive interview, including family history. Results showed that participants with OAG and previous OAG treatment reported more family history; maternal history was reported twice as often as paternal history. In persons without previous OAG treatment, those with newly diagnosed OAG reported more sibling history (Odds Ratio = 4.5). The Statistical Analysis for Genetic Epidemiology (S.A.G.E.) system was used to test the transmission models for OAG in a subset of 1,048 families (5,806 individuals) with the most complete self-reported family information. The S.A.G.E. results are consistent with the existence of a major dominant allele for OAG. These results should be viewed as promising, but preliminary, since they are based on self-reported data. More definitive information is currently being collected by the Barbados Family Study of Open-angle Glaucoma.

Open-angle glaucoma and blood groups. The Barbados Eye Study.

OBJECTIVE: To evaluate the association of open-angle glaucoma (OAG) with ABO, Rh and Duffy blood groups in the population-based Barbados Eye Study. DESIGN: Case-control study. SETTING AND PARTICIPANTS: A subset of black Barbados Eye Study participants, which included 199 OAG cases and 1063 controls. DATA COLLECTION: ABO, Rh and Duffy blood groups were determined as part of a comprehensive study visit, which included assessment for OAG through perimetry, fundus photography, and ophthalmologic examination. OUTCOME MEASURES: Comparison of blood groups between OAG cases and nonOAG controls, expressed as odds ratio and 95% confidence intervals. RESULTS: Associations were found with the Duffy Fya+ group, which is more frequent in white than black populations. In Mantel-Haenszel analyses, OAG was positively associated with Duffy Fya+ in men (odds ratio, 2.67; confidence interval, 1.52 to 4.69) and in persons with intraocular pressure more than 21 mm Hg (odds ratio, 3.32; confidence interval, 1.49 to 7.38). Logistic regression analyses confirmed these findings (interaction of Duffy Fya+ and male gender, P = .01; interaction of Duffy Fya+ and intraocular pressure, P = .04). No associations between OAG and the ABO or Rh blood groups were seen. CONCLUSIONS: The associations with Duffy Fya+, which had not been reported previously in a black population, support the involvement of genetic factors in OAG. However, the lack of association between OAG and blood group markers of African ancestry is inconsistent with a genetic explanation for the differences in OAG prevalence between blacks and whites. Our findings suggest gene-environment interactions in OAG, to be explored by further studies of OAG and Fy markers by racial group and gender.

Simulation study comparing interval estimates for the recombination fraction.

Three interval estimation procedures were evaluated to determine the method which provides the most accurate estimates for the recombination fraction, 0. The lod-0.83 support interval, the jackknife confidence interval, and the confidence interval based on estimated asymptotic standard error were compared by calculating the coverage probabilities of each. Family data that were simulated under the model of a single fully penetrant, dominant disease locus at some distance, 0, from fully informative matings were used. Comparisons were based on 1,000 random samples of size 20,60, and 100 families. In addition, a methodology for obtaining prediction intervals for 0 was developed. This procedure is of practical use and does not require asymptotic assumptions based on large sample theory. The results provide an a priori idea about precision of the estimates, as well as empirical interval estimates of 0. Graphs of the authors' Monte Carlo intervals are presented for these simulations. Investigators studying different traits, however, could condition specifically on the family structure and distribution of the disease they are investigating and obtain similar graphs.