Biomedical subjects

R J Neuman

Publications and source records attributed to R J Neuman.

6 recordsLinked to original sources

PubMed1995

Comparison of direct interview and family history diagnoses of alcohol dependence.

Using data from The Collaborative Study on the Genetics of Alcoholism, we compare direct interview diagnoses of alcohol dependence to those obtained by history from family members. Using a requirement of three or more positive implications by history, the specificity, sensitivity, and positive predictive values are 98%, 39%, and 45%, respectively. A logistic analysis found the gender of the relative and alcoholism in the informant to be significant, but not the gender of the informant. The partial odds ratio of a diagnosis at interview associated with a positive family history diagnosis was 13.6. The relationship between the informant and relative was significant, with negative reports from an offspring or mate more influential than a negative report from a parent or second-degree relative. We derived a recursive equation to combine a variable number of family history reports, wherein the probabilities associated with a single report are computed from the logistic analysis. This permits the use of family history information both as a proxy for an uninterviewed relative, as well as a second source of information to be used in the analysis of genetic family data.

Adult↗

PubMed1995

Genetic analysis of kifafa, a complex familial seizure disorder.

Kifafa is the Swahili name for an epileptic seizure disorder, first reported in the early 1960s, that is prevalent in the Wapogoro tribe of the Mahenge region of Tanzania in eastern Africa. A 1990 epidemiological survey of seizure disorders in this region reported a prevalence in the range of 19/1,000-36/1,000, with a mean age at onset of 11.6 years; 80% of those affected had onset prior to 20 years of age. A team of investigators returned to Tanzania in 1992 and collected data on > 1,600 relatives of 26 probands in 20 kifafa families. We have undertaken a genetic analysis of these data in order to detect the presence of familial clustering and whether such aggregation could be attributed to genetic factors. Of the 127 affected individuals in these pedigrees, 23 are first-degree relatives (parent, full sibling, or offspring) of the 26 probands; 20 are second-degree relatives (half-sibling, grandparent, uncle, or aunt). When corrected for age, the risk to first-degree relatives is .15; the risk to second-degree relatives is .063. These risks are significantly higher than would be expected if there were no familial clustering. Segregation analysis, using PAP (rev.4.0), was undertaken to clarify the mode of inheritance. Among the Mendelian single-locus models, an additive model was favored over either a dominant, recessive, or codominant model. The single-locus model could be rejected when compared with the mixed Mendelian model (inclusion of a polygenic background), although the major-gene component tends to be recessive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

Linkage analysis of a complex disease: application to familial Alzheimer's disease.

Evidence for linkage of the Alzheimer's gene to markers on chromosomes 19 and 21 was assessed using single-locus and two-locus models of inheritance. Families were divided into groups determined by their average age at onset. The youngest group produced higher lod scores for markers on chromosome 21 while an older group showed evidence for linkage to markers on chromosome 19. Two-locus models of disease were used to analyze the youngest group for linkage to pairs of markers on chromosome 21 and an older group with markers on chromosome 19.

Adult↗

PubMed1992

Two-locus models of disease.

Most complex diseases have not been amenable to genetic analysis under the assumption of single locus or multifactorial models. Consequently, interest has turned to the consideration of the properties of oligogenic models. i.e., genetic models involving a small number of genes. Nine two-locus models of disease, representing both epistatic and heterogeneous genetic models, are investigated: three models of heterogeneity and six models of epistatis. For each model we derive formulas for the recurrence risk to various classes of relatives in terms of penetrances and gene frequencies. We also develop formulas for the components of variance for the epistatic models in terms of the same genetic parameters. The range of penetrances and the associated gene frequencies that predict a predetermined value for the population prevalence and recurrence risk to the sibling of proband are calculated for various rates of the prevalence and risk to sibs. It is found that for many of these genetic models, there is a very limited range of penetrances that fit a particular set of assumed risks. Estimated population prevalence and risks to sibs and monozygotic twins for bipolar and schizophrenia illness are used to test for compatibility with expected values for recurrence risks under these models.

Bipolar Disorder↗

PubMed1990

Note on linkage analysis when the mode of transmission is unknown.

A major difficulty in a linkage analysis arises from the necessity of specifying the mode of inheritance prior to analysis. For a complex disease, such as those encountered in psychiatric illnesses, the mode of inheritance is generally not known in advance. Consequently, some estimation procedure is often combined with linkage analysis to circumvent this. We discuss several precautions that should be taken when using traditional statistical testing methods: correction of the likelihood for the method of sampling families and the computation of the lod score. We analyze simulated data with pedigrees selected under a sampling scheme approximating single ascertainment. In this situation, the severity of the above problems is attenuated.

Computer Simulation↗

PubMedDate not supplied

A bit about haplotypes: using binary digits to code tightly linked loci.

The advent of recombinant DNA techniques has resulted in the detection of a large number of polymorphic marker loci many of which are not useful for linkage studies because of their low degree of polymorphism. However, when no apparent recombination exists between several closely linked markers, the amount of 'information' available can be significantly increased by establishing haplotypes from those loci; that is, haplotyping increases the number of heterozygotes at marker loci. Haplotyping can be problematic when more than one of the loci involved in the haplotyping are heterozygous and the phase of the haplotypes cannot be inferred from the data. We present a method for recoding the phenotypic marker data for pedigree members that will circumvent this difficulty.

Alleles↗