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Gary A Chase

Publications and source records attributed to Gary A Chase.

28 records · Page 2Linked to original sources
PubMed2003

The major histocompatibility complex gene region and sarcoidosis susceptibility in African Americans.

Investigators have intensively evaluated the major histocompatibility (MHC) complex for sarcoidosis susceptibility genes with the majority of reports implicating the human leukocyte antigen (HLA)-DRB1 gene. Because most studies have been performed in white and Asian populations, we sought to determine which MHC genes might be risk factors for sarcoidosis in African Americans. We genotyped six microsatellite markers spanning 11.6 megabases that overlapped the MHC region on chromosome 6p21-22 in 225 nuclear families ascertained by African American probands with a history of sarcoidosis. Using a family-based association methods approach, we performed multiallelic tests of association between each marker and sarcoidosis. A statistically significant association was detected between sarcoidosis and the DQCAR marker (p = 0.002) less than two kilobases telomeric from the HLA-DQB1 gene. Typing two additional markers in this region revealed that DQCAR-G51152 haplotypes, spanning a 38-kilobase region across the HLA-DQB1 gene, were associated with sarcoidosis on a global level (p = 0.022). Analysis of individual DQCAR and G51152 alleles showed that the DQCAR 178 (expected = 21.0; observed = 10; p = 0.0005) and G51152 217 (expected = 25.6; observed = 14; p = 0.0009) alleles were transmitted to affected offspring less often than expected; whereas the DQCAR 182 allele was transmitted more often than expected (expected = 52.6; observed = 66; p = 0.002). Our results indicate that HLA-DQB1 and not HLA-DRB1 plays an important role in sarcoidosis susceptibility in African Americans. Identification of the specific HLA-DQB1 alleles that influence sarcoidosis susceptibility in African Americans and the study of their antigenic-binding properties may reveal why African Americans suffer disproportionately from this disease.

Black People↗
PubMed2003

Results of a high-resolution genome screen of 437 Alzheimer's disease families.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder of late life with complex inheritance. Mutations in three known genes lead to the rare early-onset autosomal dominant form of AD, while a common polymorphism (epsilon 4) in the gene encoding apolipoprotein E (APOE ) is a risk factor for more typical late-onset (>60 years) AD. A recent study concluded that there are up to four additional genes with an equal or greater contribution to the disease. We performed a 9 cM genome screen of 437 families with AD, the full National Institute of Mental Health (NIMH) sample, which has been carefully ascertained, evaluated and followed by our group over the last decade. Performing standard parametric and non-parametric linkage analyses, we observed a 'highly significant' linkage peak by Lander and Kruglyak criteria on chromosome 19q13, which probably represents APOE. Twelve additional locations-on 1q23, 3p26, 4q32, 5p14, 6p21, 6q27, 9q22, 10q24, 11q25, 14q22, 15q26 and 21q22-met criteria for 'suggestive' linkage [i.e. two-point lod score (TLS) >/=1.9 and/or multipoint lod score (MLS) >/=2.2] in at least one of our analyses. Although some of these will surely prove to be false positives, these linkage signals should provide a valuable framework for future studies aimed at identifying additional susceptibility genes for late-onset AD.

Aged↗
PubMed2003

Effects of covariates: a summary of Group 5 contributions.

This report summarizes the contributions of Genetic Analysis Workshop 13 (GAW13) related to the use of covariates in genetic analysis. Seven papers are summarized, five of which analyzed the Framingham Heart Study Data, and two the simulated data. Five papers examined the role of covariates in linkage analysis, using a variety of statistical approaches including affected sibling pair analysis, conditional logistic regression, and variance components methods. One paper examined the impact of covariates on family-based association analysis. In each of these papers, the detection of genetic effects could be influenced by the incorporation of covariates. The final paper examined the role of transmission ratio distortion in the analysis of complex traits and the role of covariates in the variability in transmission ratio distortion. While each paper takes a different approach to the genetic analysis of complex traits, a common thread running through each is that the inclusion of covariates can have a substantial impact on the results of the analysis. Care must be taken to understand how the covariates are being used in each analysis, what assumptions are being made, and how these assumptions might affect the results and their interpretation. Finally, the results of Group 5 studies show that inclusion of covariates can increase the power to detect genes for complex traits, and has the potential to advance an understanding of the role of genes in these complex traits.

Cardiovascular Diseases↗
PubMed2002

Gastric and duodenal safety of daily alendronate.

BACKGROUND: Isolated case reports of gastric ulcers after alendronate sodium use raised concern about the gastroduodenal safety of daily alendronate. This study was conducted to estimate the excess risk of hospitalizations for gastric or duodenal perforations, ulcers, and bleeding associated with alendronate use. PARTICIPANTS AND METHODS: Study subjects were 6432 men and women, 35 years or older. The subjects were members of 8 health maintenance organizations who were dispensed alendronate from October 1995 through September 1997. There was also a group of 33 176 age-, sex-, and health maintenance organization-matched unexposed persons. Because of concerns that osteoporosis might confound the association between alendronate use and perforation, ulcer, or bleeding, a second comparison group of 9776 women, 60 years or older, who had osteoporotic fractures was assembled. Hospitalizations for gastroduodenal events were identified by discharge diagnosis codes in automated claims records, and confirmed by manual record review. RESULTS: Based on the 14 confirmed events in the alendronate group and 35 in the unexposed group, the crude incidence rate ratio of gastroduodenal perforation, ulcer, or bleeding for the alendronate cohort was 3.0. The incidence rate ratio was 1.8 (95% confidence interval, 0.8-3.9) after control for prior hospitalizations, comorbidity, and recent exposure to prescription nonsteroidal anti-inflammatory drugs and oral corticosteroids. The crude incidence ratio rate for the age, sex, and health maintenance organizations-restricted cohort of alendronate users relative to the fracture cohort was 1.1 and the adjusted incidence rate ratio was 1.1 (95% confidence interval, 0.6-2.2). CONCLUSIONS: Osteoporosis and related factors appear to play an important role in the relationship between alendronate use and confirmed gastroduodenal perforation, ulcer, or bleeding; a substantial fraction of the increased risk we observed for alendronate users in the unadjusted analysis was the result of confounding.

Adult↗
PubMed2002

Persistence of cigarette smoking: familial liability and the role of nicotine dependence.

AIMS: It has been suggested that high genetic vulnerability may explain why smoking persists in spite of general acceptance of the health risks of cigarette smoking. Indeed, heritability estimates for smoking persistence range from 27% to 70%. It has also been suggested that genetic influences on smoking persistence may operate through nicotine dependence, which epidemiological studies have found to be an important risk factor for smoking persistence. We examined alternative ways that familial liability to persistence, nicotine dependence and smoking persistence may be related. DESIGN: Cohort study. SETTING: South-east Michigan, United States. PARTICIPANTS: A subset of 389 daily smokers informative for familial smoking characteristics from an epidemiological sample of young adults 26-35 years old (n = 979). MEASUREMENTS: Nicotine dependence criteria were assessed using the NIMH-DIS revised interview and diagnosed according to the DSM-III-R. Familial smoking characteristics were assessed by subject report. FINDINGS: Absent nicotine dependence, daily smokers with medium and high familial density of persistence were at increased risk of smoking persistence (OR = 4.2 and 7.0, respectively). However, familial density of persistence was not associated with smoking persistence among nicotine dependent daily smokers. Level of education also appeared to limit the influence of familial liability, although nicotine dependence also modified this effect. CONCLUSIONS: Nicotine dependence does not appear to be in the causal pathway from familial liability to smoking persistence, but rather modifies the association between them.

Adult↗
PubMed2002

Chronic disease score as a predictor of hospitalization.

BACKGROUND: The Chronic Disease Score is a risk-adjustment metric based on age, gender, and history of dispensed drugs. We compared four versions of the score for their ability to predict hospitalization among members of eight health maintenance organizations nationwide. METHODS: The study included 29,247 women age 45 years and older. Logistic regression models were constructed using rank quintile and rank decile indicators for each of four scores as predictors of hospitalization during the year after 1 October 1995. Discrimination and model fit were compared using several model properties including the C statistic and the odds ratio comparing highest with lowest quantiles. RESULTS: All Chronic Disease Score versions performed similarly, with the version that predicts total healthcare cost, proposed by Clark et al. (Med Care 1995;33:783-795), performing somewhat better than the other three. The overall risk of hospitalization was 12%. Individuals with higher quantile ranks had a higher risk of hospitalization. Among the Chronic Disease Score versions, the risk of hospitalization ranged from 4% for the lowest decile to 27-29% for the highest decile. Odds ratios comparing the highest with the lowest deciles ranged from 8.9 to 10.2. CONCLUSIONS: The Chronic Disease Score predicts hospitalization and therefore may be a useful indicator of baseline comorbidity for control of confounding.

Age Factors↗
PubMedDate not supplied

Contraceptive use by diabetic and obese women.

PURPOSE: Women with chronic medical conditions are at increased risk for adverse pregnancy outcomes, yet contraceptive use by these women has not been well described. The purpose of this study was to describe contraceptive use by diabetic and overweight/obese women compared with women without these conditions. METHODS: Using cross-sectional data from the 11 states participating in the optional Family Planning Module of the Behavioral Risk Factor Surveillance System in 2000, we analyzed contraceptive use among 7,943 sexually active women of reproductive age (18-44) who were not trying to conceive. Using logistic regression techniques, we modeled the effect of diabetes and overweight/obesity on contraceptive nonuse, controlling for age, race/ethnicity, marital status, education, income, and health insurance coverage. MAIN FINDINGS: Contraceptive nonuse was reported by 1,500 (18.9%) of the total sample, 31 (25.8%) diabetic women, 371 (20.0%) overweight women, and 385 (23.4%) obese women. In the multivariable model, obesity was significantly associated with contraceptive nonuse (adjusted odds ratio [OR] 1.34, 95% confidence interval [CI] 1.16-1.55), but there were no significant differences in contraceptive nonuse for diabetic women (adjusted OR 1.23, 95% CI 0.80-1.87) or overweight women (adjusted OR 1.14, 95% CI 0.99-1.31). Older, Black, Hispanic, married, less educated, and women without health insurance were more likely to report contraceptive nonuse. CONCLUSION: Among women with need for contraception, obese women were more likely to report contraceptive nonuse than normal weight women. Because women with chronic conditions like obesity are at higher risk of pregnancy-related complications and adverse pregnancy outcomes, proper contraceptive use and unintended pregnancy avoidance is a priority.

Adolescent↗
PubMedDate not supplied

Preconceptional health: risks of adverse pregnancy outcomes by reproductive life stage in the Central Pennsylvania Women's Health Study (CePAWHS).

This study used population-based data to examine how health status and risks vary by reproductive life stage, with particular focus on the proximal risks for preterm birth and low birthweight (LBW) infants in preconceptional and interconceptional women. Data are from the Central Pennsylvania Women's Health Study (CePAWHS), which included a telephone survey of a representative sample of 2,002 women ages 18-45 years residing in largely rural central Pennsylvania. Women were classified according to reproductive stage--preconceptional, interconceptional, and postconceptional--on the basis of pregnancy history and reproductive capacity. Multiple indicators of health status and health risks were examined by reproductive stage, stratified by age group (ages 18-34 and ages 35-45). Results show that many risk factors varied significantly by reproductive stage and by age group within reproductive stage. Preconceptional and interconceptional women exhibited several unhealthy behaviors (e.g., binge drinking, nutritional deficits, physical inactivity). Younger pre- and interconceptional women (ages 18-34) had more gynecologic infections, some less favorable health behaviors, and more psychosocial stress than older women (ages 35-45) in the same reproductive stages. Older preconceptional women were more likely to have chronic conditions (hypertension, high cholesterol) than younger preconceptional women. Results suggest how interventions could be tailored to women's reproductive stages.

Adult↗
PubMedDate not supplied

Physicians' propensity to offer genetic testing for Alzheimer's disease: results from a survey.

PURPOSE: Examine physician knowledge, preferences, and use of genetic tests for Alzheimer's disease (AD). METHODS: Survey of 426 community-based physicians treating AD patients. RESULTS: Majority gave inaccurate estimates of AD risk. Medical specialty predicted appropriate use of current tests. Recommending substances to prevent memory loss was related to acceptance of error-free tests. High patient loads and familiarity with genetic tests predicted lower tolerance for test error. CONCLUSION: Physicians do not endorse indiscriminate genetic susceptibility testing for AD. However, insufficient knowledge of disease risk, etiology, genetic susceptibility, and use of existing tests indicated a need for further physician education in this area.

Alzheimer Disease↗