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Biomedical subjects

R C Elston

Publications and source records attributed to R C Elston.

At least 163 records · Page 9Linked to original sources

Linkage analysis of pure depressive disease.

In a study of the subgroups of unipolar affective disease, 13 families were ascertained as pure depressive disease (PDD) families. Here we investigate linkage relationships between PDD and 30 genetic markers in these families. Using the robust sib-pair method of linkage analysis, evidence for possible linkage or association was found with five loci: the ABO and MNS blood groups, immunoglobulin kappa (IGK), proline rich parotid salivary protein (PR) and glyoxylase-1 (GLO1). Weak evidence of linkage with ABO was supported using the lod score method of analysis. The maximum lod score between PDD and ABO was 1.42 at a male recombination fraction of 0.09 and a female recombination fraction of 0.03. When these results from the sib-pair analysis were combined with the results from two previous sib-pair studies on PDD, the ABO, MNS and IGK loci were found to be significant (P = 0.05, P = 0.005, P = 0.05, respectively, not allowing for multiple tests).

Adolescent↗

Relationship of hassles, uplifts, and life events to psychological well-being of freshman medical students.

Hassles, uplifts, and life events were related to psychological well-being with a representative sample of 55 (of 179) freshman medical students. Students were sent measures of hassles, uplifts, and affect-moods measures for 9 consecutive months and a measure of life stress at the beginning and middle of the school year. The hassles measure was found to be a better predictor of concurrent and subsequent negative mood than was the life stress measure, whereas life stress was found to be a better predictor of subsequent positive mood than hassles. On the whole, uplifts were unrelated to mood. The relationship between life stress and hassles was also investigated. The implications of the findings for future stress and health outcome research are discussed.

Adaptation, Psychological↗

Oral zinc in macular degeneration.

Macular degeneration associated with age and drusen, an important cause of severe visual loss in older persons, is of unknown cause. The sensory retina and retinal pigment epithelium, which are cell layers in zinc, appear to be prominently involved in the disease process. Because zinc plays a role in the metabolic function of several important enzymes in the chorioretinal complex, we undertook a prospective, randomized, double-masked, placebo-controlled investigation of the effects of oral zinc administration on the visual acuity outcome in 151 subjects with drusen or macular degeneration. Although some eyes in the zinc-treated group lost vision, this group had significantly less visual loss than the placebo group after a follow-up of 12 to 24 months. This is the first controlled oral intervention study to show a positive, if limited, treatment effect in macular degeneration, a major public health problem. Because of the pilot nature of the study and the possible toxic effects and complications of oral zinc administration, widespread use of zinc in macular degeneration is not now warranted.

Administration, Oral↗

Familial risk of cancer among randomly selected cancer probands.

Several investigators have reported that relatives of lung cancer probands have a greater-than-normal likelihood for developing some form of cancer. To evaluate whether this familial risk is general for probands with cancer at any site or limited to lung cancer probands, we did a case-control study in which probands having cancer affecting any body site were identified and their pedigree data were tabulated. Telephone interviews and a mailed questionnaire were used to obtain cancer histories and environmental exposures on the families of 41 lung cancer probands, 105 probands with cancer other than lung, and 127 spouse families. Cumulative tobacco exposure (P less than .05), occupational hazards (P less than .005), and age of the family relatives (P less than .0001) were found to be statistically significant predictors of cancer risk. With consideration given for these variables, we determined that siblings of lung cancer probands were at slightly greater risk of cancer of any kind (odds ratio [OR] = 1.43, P = .06) than siblings in the control group. Much of the elevated risk was attributable to an excess of lung cancer (OR = 2.49, P = .06). Siblings of non-lung/non-breast cancer probands were also determined to be at increased risk of lung cancer as well (OR = 1.61, P = .06). For parents, the risk was lower, although parental information may have been underreported.

Family↗

Evidence for possible linkage between genetic markers and affective disorders.

Studies of the underlying components of affective disorders are particularly difficult because of the confounding effects of both genetic and environmental factors. Linkage analysis is a useful tool in delineating the etiology of affective disorders, as it is unlikely that linkage between behavioral traits and blood group polymorphisms could result from environmental effects. The present study used the robust Haseman and Elston sibpair method to analyze linkage between 24 genetic markers and affective disorder in 34 nuclear families from 25 pedigrees (195 people). The probands were ascertained as part of the ongoing NIMH Collaborative Depression Study. Indications of linkage between familial pure depressive disease and MNS and depression spectrum disease and ORM were found, as had been previously suggested. There was also suggestive evidence for linkage between the latter and GC. Results are discussed in terms of methodological differences with previous studies.

Bipolar Disorder↗

Possible linkage between alcoholism and esterase-D.

Association and linkage relationships between alcoholism and 30 polymorphic marker loci were studied in a total of 42 families: 27 families originally collected as part of a study on depression spectrum disease, 14 previously reported families with depression spectrum disease, and 1 family with familial alcoholism. Since heterogeneity within a sample can confound genetic linkage analysis, obscuring linkage relationships, alcoholism was studied in these families as a disorder unrelated to depression or antisocial personality. No allelic associations were found to be significant after allowing for the multiple tests. In a sib-pair linkage analysis, significant differences between the mean proportion of genes identical by descent in concordant and discordant sib pairs were found for the esterase-D (ESD) marker locus (p less than or equal to .01). This suggested that a linkage may exist between a gene for alcoholism and the ESD locus on chromosome 13q. Lod score linkage analysis yielded odds in favor of linkage to ESD of 44 to 1, most of the information relevant to linkage residing in a single family in which three offspring were classified as alcoholic and five were not.

Adult↗

Linkage of a gene regulating dopamine-beta-hydroxylase activity and the ABO blood group locus.

Previous studies have presented evidence suggesting that levels of dopamine-beta-hydroxylase (DBH) activity are controlled by a gene linked to the ABO blood group locus. In this study, linkage analyses in four large families of whites and one family of blacks were performed on the untransformed and on the square root--and natural log--transformed DBH activity. In the families of white individuals, the results of both the sib-pair and lod-score linkage analyses strongly indicate that a gene regulating DBH activity is linked to the ABO blood group locus on chromosome 9q (i.e., lod score 5.88 at a recombination fraction of .0). However, the transformation used has a large effect on the maximum lod score and estimated recombination fraction. This putative gene does not appear to be polymorphic in the family of blacks.

ABO Blood-Group System↗

A linkage study of panic disorder.

We tested for linkage between panic disorder and a battery of 29 genetic markers in 26 families. Linkage between panic disorder and 18 of the marker loci could be excluded at a recombination fraction of 0.00, nine at a recombination fraction of 0.05, and four at a recombination fraction of 0.10. The 18 loci are distributed over ten chromosomes. One locus was suggestive of linkage. The maximum lod score for alpha-haptoglobin was 2.27 at a recombination fraction of 0.0, representing odds in favor of linkage of 186.1. alpha-Haptoglobin has been mapped to chromosome 16q22. The results demonstrate that linkage studies of psychiatric disorders can yield informative results by identifying tentative linkages that merit further investigation and by excluding regions of the genome from future linkage searches.

Adult↗

Genetic analysis of serum lipid levels and blood pressure in a large kindred.

A 267-member Caucasian kindred with a high incidence of cardiovascular disease, originally from Evans County, Georgia, was chosen for genetic analysis of serum lipid levels and blood pressure. Total serum cholesterol, triglycerides, high density lipoprotein cholesterol (HDL), and systolic and diastolic blood pressures were natural logarithm transformed and then adjusted for significant age, sex, and behavioral trait effects. Major gene pedigree analysis was used to estimate genetic parameters and to test hypotheses about the mode of transmission of each trait. Multivariate methods were also used to estimate linear combinations of the variables that best fit genetic models. The data were consistent with a major gene segregating for high levels of triglycerides in this kindred. However, dominant and recessive hypotheses could not be distinguished. Although diastolic blood pressure fit a mixture of two distributions significantly better than a single normal, major gene hypotheses could be rejected while the no-transmission hypothesis could not. There was no evidence of a major gene effect on cholesterol, HDL, systolic blood pressure, or any of the hypothetical traits represented by linear functions of the physical-lipid traits.

Adult↗

Segregation and linkage analyses of dopamine-beta-hydroxylase activity in a six-generation pedigree.

Serum dopamine-beta-hydroxylase (DBH) levels and 30 polymorphic markers were determined on 178 individuals of the HGAR 29 family, ascertained through six probands who had clinical and electrocardiographic evidence of myocardial infarction. Individuals in this pedigree with a history of heart attack had significantly lower levels of DBH, but this difference was partly confounded with age differences. Pedigree segregation analysis showed evidence of a codominant gene for DBH segregating in the family. Linkage analysis between the putative DBH locus and 30 polymorphic marker loci, assuming a codominant model, yielded a largest lod score of 0.53, with ABO at 20% recombination. Adding this to the lod scores obtained by Elston et al [1979] and Goldin et al [1982], we obtain combined lod scores of 2.49 and 2.50 at 0.0 and 10% recombination respectively.

ABO Blood-Group System↗

A major gene model for the familial aggregation of plasma IgA concentration.

Plasma IgA concentration was determined on 94 individuals of an eastern Kentucky family (IGANI) with some members having clinical and biopsy-proven IgA nephropathy, and on 197 individuals of a large Louisiana family (HGAR29) with no clinical history of IgA nephropathy but on whom 30 polymorphic markers had previously been typed. Pedigree segregation analysis was used to fit a major gene model, and a moderately large lod score for linkage to the ABO locus (1.50 at 0% recombination) suggested the existence of a recessive allele for high plasma IgA concentration. This allele is only slightly more prevalent in pedigree IGANI than in pedigree HGAR29, indicating that it is a minor, rather than a major, etiologic factor in IgA nephropathy.

Adult↗