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Background Parkinson’s disease (PD) is a disease of the central nervous system that progressively affects the motor system. Epidemiological studies have provided evidence that exposure to agriculture-related occupations or agrichemicals elevate a person’s risk for PD. Here, we sought to examine the possible epigenetic changes associated with working on a plantation on Oahu, HI and/or exposure to organochlorines (OGC) in PD cases. Results We measured genome-wide DNA methylation using the Illumina Infinium HumanMethylation450K BeadChip array in matched peripheral blood and postmortem brain biospecimens in PD cases (n = 20) assessed for years of plantation work and presence of organochlorines in brain tissue. The comparison of 10+ to 0 years of plantation work exposure detected 7 and 123 differentially methylated loci (DML) in brain and blood DNA, respectively ( p  < 0.0001). The comparison of cases with 4+ to 0–2 detectable levels of OGCs, identified 8 and 18 DML in brain and blood DNA, respectively ( p  < 0.0001). Pathway analyses revealed links to key neurotoxic and neuropathologic pathways related to impaired immune and proinflammatory responses as well as impaired clearance of damaged proteins, as found in the predominantly glial cell population in these environmental exposure-related PD cases. Conclusions These results suggest that distinct DNA methylation biomarker profiles related to environmental exposures in PD cases with previous exposure can be found in both brain and blood.

Background Admixture mapping is a powerful gene mapping approach for an admixed population formed from ancestral populations with different allele frequencies. The power of this method relies on the ability of ancestry informative markers (AIMs) to infer ancestry along the chromosomes of admixed individuals. In this study, more than one million SNPs from HapMap databases and simulated data have been interrogated in admixed populations using various measures of ancestry informativeness: Fisher Information Content (FIC), Shannon Information Content (SIC), F statistics (F ST ), Informativeness for Assignment Measure (I n ), and the Absolute Allele Frequency Differences (delta, δ). The objectives are to compare these measures of informativeness to select SNP markers for ancestry inference, and to determine the accuracy of AIM panels selected by each measure in estimating the contributions of the ancestors to the admixed population. Results F ST and I n had the highest Spearman correlation and the best agreement as measured by Kappa statistics based on deciles. Although the different measures of marker informativeness performed comparably well, analyses based on the top 1 to 10% ranked informative markers of simulated data showed that I n was better in estimating ancestry for an admixed population. Conclusions Although millions of SNPs have been identified, only a small subset needs to be genotyped in order to accurately predict ancestry with a minimal error rate in a cost-effective manner. In this article, we compared various methods for selecting ancestry informative SNPs using simulations as well as SNP genotype data from samples of admixed populations and showed that the I n measure estimates ancestry proportion (in an admixed population) with lower bias and mean square error.

The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study is a national, population-based, longitudinal study of 30,000 African-American and white adults aged ≧45 years. The objective is to determine the causes for the excess stroke mortality in the Southeastern US and among African-Americans. Participants are randomly sampled with recruitment by mail then telephone, where data on stroke risk factors, sociodemographic, lifestyle, and psychosocial characteristics are collected. Written informed consent, physical and physiological measures, and fasting samples are collected during a subsequent in-home visit. Participants are followed via telephone at 6-month intervals for identification of stroke events. The novel aspects of the REGARDS study allow for the creation of a national cohort to address geographic and ethnic differences in stroke.

Recent studies suggest that insulin-degrading enzyme (IDE) in neurons and microglia degrades Aβ, the principal component of β-amyloid and one of the neuropathological hallmarks of Alzheimer's disease (AD). We performed parametric and nonparametric linkage analyses of seven genetic markers on chromosome 10q, six of which map near the IDE gene, in 435 multiplex AD families. These analyses revealed significant evidence of linkage for adjacent markers (D10S1671, D10S583, D10S1710, and D10S566), which was most pronounced in late-onset families. Furthermore, we found evidence for allele-specific association between the putative disease locus and marker D10S583, which has recently been located within 195 kilobases of the IDE gene.

Background New technologies make it possible for the first time to genotype hundreds of thousands of SNPs simultaneously. A wealth of genomic information in the form of publicly available databases is underutilized as a potential resource for uncovering functionally relevant markers underlying complex human traits. Given the huge amount of SNP data available from the annotation of human genetic variation, data mining is a reasonable approach to investigating the number of SNPs that are informative for ancestry information. Methods The distribution and density of SNPs across the genome of African and European populations were extensively investigated by using the HapMap, Affymetrix, and Illumina SNP databases. We exploited these resources by mining the data available from each of these databases to prioritize potential candidate SNPs useful for admixture mapping in complex human diseases and traits. Over 4 million SNPs were compared between Africans and Europeans on the basis of a pre-specified recommended allele frequency difference (delta) value of ≥ 0.3. Results The method identified 15% of HapMap, 11% of Affymetrix, and 14% of Illumina SNP sets as candidate SNPs, termed ancestry informative markers (AIMs). These AIM panels with assigned rs numbers, allele frequencies in each ethnic group, delta value, and map positions are all posted on our website http://www.ssg.uab.edu/downloads/admixture_mapping/SNPAIMs.txt . All marker information in this data set is freely and publicly available without restriction. Conclusion The selected SNP sets represent valuable resources for admixture mapping studies. The overlap between selected AIMs by this single measure of marker informativeness in the different platforms is discussed.

Ensuring adequate representation of all demographic groups in medical research is necessary in order to ensure that the benefits associated with participation are equitably shared. Mental health research is unique in that the stigma associated with mental illness, such as schizophrenia, further hinders participation. Using focus groups, we set out to explore the attitudes and views of African Americans with regard to schizophrenia and medical research. Four focus group discussions were conducted, with 23 participants divided into two groups of working and retired adults, and two groups of full- and part-time students selected from inner-city residents of Birmingham, AL, and surrounding counties. Data obtained were analyzed using the content analysis method. Diverse views were expressed about the cause of mental illness, and much of this was influenced by cultural beliefs. There was considerable misunderstanding of schizophrenia, and the majority of participants described the disease in terms of positive symptoms only. Whereas for older participants the Tuskegee syphilis study experience was an important factor in their reluctance to participate in medical research, younger participants expressed no knowledge of the study. Among younger participants an assumed level of social distrust was evident, with prominent fear of participating in research that employs physically intrusive methods. The provision of accurate information through trusted community sources and open dialogue will help to dispel myths, correct faulty assumptions and increase African-American participation in schizophrenia research.

Prevalence and Risk Factors of Microalbuminuria in a Cohort of African-American Women With Gestational Diabetes Rodney C.P. Go , PHD 1 , Renee Desmond , PHD 2 , Jeffrey M. Roseman , MD, PHD, MPH 1 , David S.H. Bell , MD 3 , Chotip Vanichanan , MD 4 and Ronald T. Acton , PHD 4 1 Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama 2 Biostatistics Unit, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama 3 Division of Endocrinology and Metabolism, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 4 Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama Abstract OBJECTIVE —To study the prevalence of microalbuminuria (MA) in African-American women with a history of gestational diabetes (GDM) who are at high risk for insulin resistance and renal dysfunction and to study MA’s relation to insulin resistance, type 2 diabetes, and hypertension. RESEARCH DESIGN AND METHODS —MA was assessed using 24-h, timed, and/or random urine samples in a cross-sectional sample ( n = 289) from a cohort of African-American women with a history of GDM and followed for a median of 11 years (range 3.0–18.4) since their diabetic pregnancy. Subjects with a urine albumin excretion rate of 30–300 g/24 h or 30–300 μg/mg creatinine in a random sample were classified as having MA if two of three samples over a 3- to 6-month period were positive. These women were evaluated for family history of diabetes, smoking and alcohol use, BMI, diabetes, hypertension, and lipid abnormalities. Insulin sensitivity was determined using the homeostasis model assessment (HOMA) estimates, which used fasting insulin and glucose measurements obtained at the same time as the MA urine sample. RESULTS —At MA assessment, the women ranged in age from 22 to 57 years, with a median of 39 years. The overall prevalence of MA was 20%; 36% in those with diabetes. Those women with MA had higher rates of diabetes (63.8 vs. 28.6%, odds ratio [OR] = 4.4, P < 0.05), hypertension (82.8 vs. 42.9%, OR = 6.4, P < 0.05), and family history of diabetes (85.7 vs. 61.7%, OR = 3.7, P < 0.05). The proportion of subjects with MA with a family history of hypertension was nonsignificantly increased (92.9 vs. 82.4%). Subjects with MA were more obese (BMI 37.2 ± 8.9 vs. 34.4 ± 8.6 kg/m 2 ) and had higher levels of HbA 1c (8.8 ± 3.3 vs. 6.6 ± 1.8%, P < 0.001) and systolic (144.3 ± 25.9 vs. 122.8 ± 17.2 mmHg, P < 0.0001) and diastolic (95.1 ± 15.4 vs. 82.5 ± 11.9 mmHg, P < 0.0001) blood pressures. Lipid fractions were similar in those with and without MA. Although fasting glucose was much higher in subjects with MA (10.3 ± 5.8 vs. 7.1 ± 4.2 mmol/l, P = 0.0002), insulin levels were not significantly higher in subjects with MA (17.4 ± 21.2 vs. 15.2 ± 12.4 pmol/l). Insulin sensitivity, as measured using log HOMA, was similar (1.5 ± 0.6 vs. 1.6 ± 0.6) in women with and without MA, respectively. Multivariable logistic regression analyses indicated that HbA 1c , OR = 1.16 (1.07, 1.27), and systolic blood pressure, OR = 1.27 (1.14, 1.41), were independent risk factors for MA. In those with diabetes, the subjects with MA had higher rates of hypertension—83.8 vs. 56.1%, OR = 4.1 (1.5, 11.10)—which was reflected by their higher systolic and diastolic blood pressures, 146.1 mmHg ( P = 0.001) and 94.8 mmHg ( P = 0.002), respectively, and lower levels of VLDL (0.45 ± 0.22 vs. 0.61 ± 0.33 mmol/l, P = 0.021). In the multivariable analyses of those with diabetes, the two independent risk factors for MA were similar: HbA 1c , OR = 1.13 (1.01, 1.28), and systolic blood pressure, OR = 1.21 (1.04, 1.41). CONCLUSIONS —African-American women with a history of GDM have one of the highest rates for MA. Presence of MA was not associated with insulin resistance but was significantly independently associated with HbA 1c levels and hypertension. These results, taken in context of the literature, suggest that hypertension and glucose intolerance, in part, influence MA through different mechanisms. Because of the high prevalence of MA in this population and MA’s relation to all-cause and cardiovascular mortality, screening for MA should be considered. CVD, cardiovascular disease ESRD, end-stage renal disease GDM, gestational diabetes HOMA, homeostasis model assessment MA, microalbuminuria OR, odds ratio POR, prevalence odds ratio Footnotes Address correspondence and reprint requests to Rodney C.P. Go, PhD, Department of Epidemiology and International Health, School of Public Health, 1665 University Blvd., Ryals Public Health Bldg, Room 230N, Birmingham, AL 35294-0022. E-mail: rgo{at}uab.edu . Received for publication 22 February 2001 and accepted in revised form 6 July 2001. A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

Cardiovascular disease (CVD) is a designation for multiple clinical phenotypes that result from the interaction of genetic variants, lifestyle choices, and environmental exposures. This article points to the utility of assessing a person's family history of CVD, which is the sum of genetic factors, environment and common lifestyle influences, which may be shared among family members and provides information useful for estimating risk for CVD. It also presents several approaches utilized in attempts to identify variants in genes that are involved in the etiology of CVD. Specifically, examples of the candidate gene approach to identify genetic risk factors for coronary heart disease from our own research are presented. The utilization of genetic profiling to predict an individual's long-term prognosis, to target preventive strategies, and to select the most efficacious drug for treatment are discussed, as well as, the need to consider newer approaches to understanding complex diseases.

The patterns of the occurrence of breast cancer in 11 high-risk families were evaluated by segregation and linkage analysis. These patterns were consistent with the hypothesis that increased susceptibility to breast cancer was inherited as an autosomal dominant allele with high penetrance in women. The postulated susceptibility allele in these families may be chromosomally linked to the glutamate-pyruvate transaminase (E.C. 2.6.1.2, alanine aminotransferase) locus. Confirmation of this linkage in other families would establish the existence of a gene increasing susceptibility to breast cancer. Since there is no association in the general population between a woman's glutamate-pyruvate transaminase genotype and her cancer risk, the glutamate-pyruvate transaminase linkage cannot be used as a screening test for breast cancer.