Genes, age, and alcoholism: analysis of GAW14 data

A genetic analysis of age of onset of alcoholism was performed on the Collaborative Study on the Genetics of Alcoholism data released for Genetic Analysis Workshop 14. Our study illustrates an application of the log-normal age of onset model in our software Genetic Epidemiology Models (GEMs). The phenotype ALDX1 of alcoholism was studied. The analysis strategy was to first find the markers of the Affymetrix SNP dataset with significant association with age of onset, and then to perform linkage analysis on them. ALDX1 revealed strong evidence of linkage for marker tsc0041591 on chromosome 2 and suggestive linkage for marker tsc0894042 on chromosome 3. The largest separation in mean ages of onset of ALDX1 was 19.76 and 24.41 between male smokers who are carriers of the risk allele of tsc0041591 and the non-carriers, respectively. Hence, male smokers who are carriers of marker tsc0041591 on chromosome 2 have an average onset of ALDX1 almost 5 years earlier than non-carriers

A study of genetic association with electrophysiological measures related to alcoholism: GAW14 data

Recently, alcohol-related traits have been shown to have a genetic component. Here, we study the association of specific genetic measures in one of the three sets of electrophysiological measures in families with alcoholism distributed as part of the Genetic Analysis Workshop 14 data, the NTTH (non-target case of Visual Oddball experiment for 4 electrode placements) phenotypes: ntth1, ntth2, ntth3, and ntth4. We focused on the analysis of the 786 Affymetrix markers on chromosome 4. Our desire was to find at least a partial answer to the question of whether ntth1, ntth2, ntth3, and ntth4 are separately or jointly genetically controlled, so we studied the principal components that explain most of the covariation of the four quantitative traits. The first principal component, which explains 70% of the covariation, showed association but not genetic linkage to two markers: tsc0272102 and tsc0560854. On the other hand, ntth1 appeared to be the trait driving the variation in the second principal component, which showed association and genetic linkage at markers in four regions: tsc0045058, tsc1213381, tsc0055068, and tsc0051777 at map distances 53.26, 85.42, 89.31, and 172.86, respectively. These results show that the partial answer to our starting question for this brief analysis is that the NTTH phenotypes are not jointly genetically controlled. The component ntth1 displays marked genetic linkage

Cardiovascular reactivity in Zimbabwe

Objective. In this study, we examined the effects of residency and gender on cardiovascular reactivity to a speech stressor in 50 rural Zimbabweans (24 males, 26 females) and 47 urban Zimbabweans (25 males and 22 females). Methods. Participants were engaged in 4 periods: pre-task rest period, speech preparatory period, speaking task period, and the final recovery period. During each period, systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were assessed. Results. There was a significant interaction between area of residence and period for SBP and HR. Urban residents exhibited greater SBP and HR during the speaking phase of the speech task than did rural residents. However, rural residents displayed more exaggerated HR reactivity during the speech preparatory phase as compared to the urban residents. No gender differences were observed on blood pressure or heart rate reactivity. Conclusion. In conclusion, the more exaggerated SBP and HR reactivity to the speaking phase among urban residents as compared to rural residents may be influenced by factors associated with urbanization

Racial discrimination and breast cancer incidence in US Black women

Perceived discrimination may contribute to somatic disease. The association between perceived discrimination and breast cancer incidence was assessed in the Black Women\u27s Health Study. In 1997, participants completed questions on perceived discrimination in two domains: everyday discrimination (e.g., being treated as dishonest) and major experiences of unfair treatment due to race (job, housing, and police). Cox proportional hazards models were used to estimate incidence rate ratios, controlling for breast cancer risk factors. From 1997 to 2003, 593 incident cases of breast cancer were ascertained. In the total sample, there were weak positive associations between cancer incidence and everyday and major discrimination. These associations were stronger among the younger women. Among women aged less than 50 years, those who reported frequent everyday discrimination were at higher risk than were women who reported infrequent experiences. In addition, the incidence rate ratio was 1.32 (95% confidence interval: 1.03, 1.70) for those who reported discrimination on the job and 1.48 (95% confidence interval: 1.01, 2.16) for those who reported discrimination in all three situations - housing, job, and police - relative to those who reported none. These findings suggest that perceived experiences of racism are associated with increased incidence of breast cancer among US Black women, particularly younger women. Copyright © 2007 by the Johns Hopkins Bloomberg School of Public Health All rights reserved

Stickler syndrome caused by COL2A1 mutations: genotype–phenotype correlation in a series of 100 patients

Stickler syndrome is an autosomal dominant connective tissue disorder caused by mutations in different collagen genes. The aim of our study was to define more precisely the phenotype and genotype of Stickler syndrome type 1 by investigating a large series of patients with a heterozygous mutation in COL2A1. In 188 probands with the clinical diagnosis of Stickler syndrome, the COL2A1 gene was analyzed by either a mutation scanning technique or bidirectional fluorescent DNA sequencing. The effect of splice site alterations was investigated by analyzing mRNA. Multiplex ligation-dependent amplification analysis was used for the detection of intragenic deletions. We identified 77 different COL2A1 mutations in 100 affected individuals. Analysis of the splice site mutations showed unusual RNA isoforms, most of which contained a premature stop codon. Vitreous anomalies and retinal detachments were found more frequently in patients with a COL2A1 mutation compared with the mutation-negative group (P<0.01). Overall, 20 of 23 sporadic patients with a COL2A1 mutation had either a cleft palate or retinal detachment with vitreous anomalies. The presence of vitreous anomalies, retinal tears or detachments, cleft palate and a positive family history were shown to be good indicators for a COL2A1 defect. In conclusion, we confirm that Stickler syndrome type 1 is predominantly caused by loss-of-function mutations in the COL2A1 gene as >90% of the mutations were predicted to result in nonsense-mediated decay. On the basis of binary regression analysis, we developed a scoring system that may be useful when evaluating patients with Stickler syndrome