Biomedical subjects

R J Neuman

Publications and source records attributed to R J Neuman.

29 records · Page 2Linked to original sources

PubMed1998

Latent class and factor analysis of DSM-IV ADHD: a twin study of female adolescents.

OBJECTIVE: In an attempt to validate the current DSM-IV criteria for attention-deficit/hyperactivity disorder (ADHD) in females and to determine whether symptoms are continuously distributed or categorically discrete, the authors performed factor and latent class analysis on ADHD symptom data from a large general population of adolescent female twins (1,629 pairs). METHOD: A structured diagnostic assessment of DSM-IV ADHD was completed with at least one parent of 1,629 pairs by telephone. ADHD symptoms from 1,549 pairs were subjected to latent class and factor analysis. RESULTS: Latent class and factor analyses were consistent with the presence of separate continuous domains of inattention (ATT), hyperactivity-impulsivity (H-I), and combined ATT with H-I problems. Severe latent classes corresponding to the predominantly inattentive, predominantly hyperactive-impulsive, and combined types were identified with lifetime prevalence estimates of 4.0%, 2.2%, and 3.7%, respectively. Membership in the severe ATT class predicted academic problems, family problems, and referral to health care providers. Membership in the H-I and combined classes also predicted impaired social relationships. CONCLUSIONS: These results suggest that DSM-IV ADHD subtypes can be thought of as existing on separate continua of inattention, hyperactivity-impulsivity, and combined type problems. Membership in any of there severe ADHD latent classes did not preclude academic excellence, but it was associated with different types of impairment and health care-seeking behavior. These data have implications in the areas of diagnosis, classification, treatment, and research.

Adolescent↗

PubMed1998

Linkage of an alcoholism-related severity phenotype to chromosome 16.

There is substantial evidence for a significant genetic component to the risk for alcoholism. In searching for genes that contribute to this risk, the diagnostic criteria for alcohol dependence may not be the optimal phenotype; rather, creation of a more homogeneous phenotype will lead to a more homogeneous genetic etiology. Items from the Semi-Structured Assessment for the Genetics of Alcoholism collected from 830 individuals in 105 alcoholic families were used in a latent class analysis to identify a more homogeneous alcoholism-related phenotype. A four-class solution was chosen: class 1, unaffected group; class 2, mildly problematic group; class 3, moderately affected group; and class 4, severely affected group. Classes 3 and 4 had higher symptom endorsement probabilities than classes 1 and 2 for items reflecting severe alcohol dependence, and were combined to provide enough sibling pairs for genetic linkage analysis. A total of 291 markers distributed throughout the genome, with an average intermarker distance of 14 cM, were genotyped. Linkage analysis was performed to detect loci underlying classes 3 and 4, the moderately and severely affected alcoholics, of whom 88% met the Collaborative Study of the Genetics of Alcoholism, and >99% met ICD-10 criteria for alcohol dependence. Evidence for a locus on chromosome 16, near the marker D16S675, was found with a maximum multipoint lod score of 4.0. Analysis of additional markers on chromosome 16 yielded a lod score of 3.2, narrowed the critical region, and placed the gene between D16S475 and D16S675 in a 15 cM interval.

Adult↗

PubMed1997

Testing the utility of mod scores and sib-pair analysis to detect presence of disease susceptibility loci.

Linkage analyses and association studies were employed to detect disease susceptibility loci leading to elevated Q1 levels in Problem 2B. Phenotypes were defined to be the dichotomous affection status, the quantitative value for Q1, and Q1 adjusted for covariates. The method of mod-scores (for the dichotomous phenotype) and the Haseman-Elston sib-pair test on the dichotomous and quantitative phenotypes were used to screen for linkage of disease susceptibility genes to 367 markers. These analyses were performed on a sample ascertained from the first 60 replicates. The mod-score method detected linkage to MG1, MG2, and MG3 with scores of 1.5, 5.0, and 1.6 respectively. Sib-pair analysis using quantitative phenotypes signaled linkage only to the area surrounding MG1; the dichotomous phenotype detected linkage only to MG2. Association studies used ANOVA on all founders in the first 60 replicates and ASSOC on the ascertained families and on a subset of families from the 60 replicates but only confirmed an association to MG1. In conclusion, the mod-score method may be a useful tool for genomic screens.

Analysis of Variance↗

PubMed1997

Increased prevalence and earlier onset of mood disorders among relatives of prepubertal versus adult probands.

OBJECTIVE: To compare the familial clustering of affective disorders among first-degree relatives of prepubertal versus adult probands with mood disorders. METHOD: The Family History-Research Diagnostic Criteria (FH-RDC) assessment instrument was used to obtain data on first-degree relatives of all probands. Logistic regression was used to assess the strength of the age of the proband to predict FH-RDC diagnoses in relatives. Survival analysis was used to examine the age-at-onset distribution of first FH-RDC diagnosis while controlling for year of birth. RESULTS: The prevalence of major affective disorders was more than two times higher among first-degree relatives of child probands versus those of adult probands even when controlling for birth cohort. Cumulative risk for lifetime major mood disorders in first-degree relatives of child probands was significantly higher than for those of adult probands. CONCLUSION: These analyses further support that ascertainment of families through affected children identifies pedigrees with a higher proportion of affected relatives than ascertainment through affected adults.

Adult↗

PubMed1995

TDT with covariates and genomic screens with mod scores: their behavior on simulated data.

We describe an extension to the TDT (transmission/disequilibrium test) which allows for more than two marker alleles and for covariates measured on the parent or offspring. We also describe a systematic genomic search where the mod score (maximized lod score) is computed for each marker under constraints on the population prevalence or penetrances of a single locus.

Computer Simulation↗

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↗