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Biomedical subjects

J P Rice

Publications and source records attributed to J P Rice.

At least 19 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

Familial aspects of prostate cancer: a case control study.

PURPOSE: We evaluated the importance of positive family history, age at diagnosis and history of vasectomy in predicting the risk for prostate cancer in the brothers of prostate cancer patients. MATERIALS AND METHODS: A total of 1,084 men with newly diagnosed prostate cancer responded by interview to a family history survey, which included detailed information on the diagnosis of any cancer in the parents of the proband, diagnosis of prostate cancer in male relatives and age at onset of prostate cancer in the proband. A history of vasectomy was also obtained from the proband. The control cases consisted of 935 spouses of the probands who were administered the same questionnaire in an identical fashion. RESULTS: Prostate cancer was not significantly associated with other types of cancer in proband parents. The presence of prostate cancer in the father, grandfather or uncle of the proband significantly increased the risk of prostate cancer in proband brothers. Early age at onset in the proband was also associated with an increased risk to the proband brothers. CONCLUSIONS: Men with a family history of prostate cancer are at a significantly increased risk for prostate cancer, especially if the affected relative had early onset of cancer. Prostate cancer does not seem to be associated with a higher incidence of other cancers in family members.

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↗
PubMed1994

Latent structure of DSM-III-R Axis II psychopathology in a normal sample.

The Personality Disorder Examination was administered to 302 normal controls in the New York High-Risk Project in order to elicit Axis II diagnoses (revised 3rd edition of the Diagnostic and Statistical Manual of Mental Disorders; American Psychiatric Association, 1987) and quantitative dimensions of psychopathology. LISREL confirmatory factor analysis was used to evaluate the Axis II hypothesis of 3 orthogonal factors. There was considerable overlap among personality disorders. The best fitting LISREL model was of 3 oblique factors that were different for male and female subjects. Given that our choice of variables to constrain in order to mathematically identify our models was partially based on analysis of intercorrelations in our data set, our methods were not purely confirmatory. We present our results not to confirm specific hypotheses but to generate explicit hypotheses that can be tested in independent samples.

Adolescent↗
PubMed1994

Stability of diagnosis: application to phenotype definition.

Using diagnostic stability data from independent diagnostic interviews conducted 6 years apart, we determine which diagnoses are predictive of diagnoses 6 years later. Logistic analysis using categorical predictors is used to establish ordinal relationships and to suggest diagnostic hierarchies. The multiple-threshold multifactorial model is used to estimate the within-person correlation over time. Rather than use a simple dichotomy of "affected" or "unaffected," we provide odds ratios for mania, hypomania, and major depressive disorder in terms of diagnostic hierarchies, allowing a ranking of these diagnoses. This division increases the information for genetic studies or studies of a phenotype with correlated biological or environmental continuous covariates. The diagnosis of schizophrenia shows remarkable specificity across occasions. We find significant error in a cross-sectional assessment in this nonclinical sample. Assuming a multifactorial model, the proportion of variance in liability due to assessment error is approximately 30 percent under all schemes considered. The use of repeated measures in family studies is thus strongly recommended.

Bipolar Disorder↗
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↗
PubMed1993

Phenotype definition for genetic studies.

A difficulty in the interpretation of the reliability/stability of a lifetime diagnosis of mental disorders is the lack of a theoretical perspective. A model expressed in terms of the three unknowns-sensitivity, specificity and true base rate--is problematic due to the lack of a "gold standard", so that only two of these unknowns can be estimated. We extend this model to allow for clinical covariates that increase the likelihood that a positive case at Time 1 will be positive at Time 2. Under the assumption that all observed cases are true cases at the highest covariate values, we obtain a direct estimate of the sensitivity, so that all unknowns can be estimated. Moreover, we then calculate the likelihood that an observed case with given covariate levels is in fact a true case. The implications of diagnostic error for the fitting of genetic models are given. These methods are applied to stability data collected as part of the NIMH Psychobiology of Depression Program. A total of 1,629 relatives have been assessed with interviews separated by a 6-year interval. A logistic function was used to model the stability in relatives with an initial lifetime diagnosis of affective disorders. We discuss the use of these techniques in genetic models to increase information by defining an ordinal phenotype, use multiple assessments to minimize the impact of diagnostic error and increase the heritability, and utilize clinical covariates to model the certainty of diagnosis.

Humans↗
PubMed1993

Association between major depressive disorder and physical illness.

The association between major depressive disorder (MDD) and self-reported histories of specific physical illnesses was investigated in 320 controls and 1968 first-degree relatives and 254 spouses of probands in the NIMH Collaborative Depression study. The Schedule for Affective Disorders and Schizophrenia-Lifetime Version was used to assign Research Diagnostic Criteria (RDC) diagnoses and a structured self-report instrument was used to assess lifetime medical history. Lifetime MDD was diagnosed in 914 subjects, 402 of whom had been hospitalized or received somatic treatment ('treated' MDD). Strong associations were observed between MDD (either treated or untreated) and both frequent/severe headaches and migraine headaches. There was a marked gender effect such that the relative odds for a woman with treated MDD to report migraine were over 5:1. Other associations were found between MDD and skin infections, respiratory illness, ulcer, hypotension, and diabetes. This is the largest non-patient sample using standardized assessment of mental disorders by direct interview in which associations between specific physical illnesses and MDD have been demonstrated. Implications for clinical practice and neurobiological research in depression are discussed.

Adolescent↗
PubMed1992

Stability of psychiatric diagnoses. An application to the affective disorders.

In the National Institute of Mental Health Collaborative Program on the Psychobiology of Depression study, data were collected on 2226 first-degree relatives of 612 probands. A second, "blind" reassessment of all relatives was attempted 6 years after the initial evaluation. We report on a final sample of 1629 relatives assessed twice using the Schedule for Affective Disorders and Schizophrenia-Lifetime version. We summarize methods for using stability of diagnosis to model the relationship between clinical covariates and the probability of being a true case. Moreover, we define an index of caseness that can be used to narrow the criteria for who is a case. Of those positive for major depressive disorder at initial evaluation, 74% were positive (on a lifetime basis) at follow-up (ie, were stable). There is a gradient: 48% of those who had three symptoms and no treatment were stable, compared with 96% of those with eight symptoms and treatment. For major depressive disorder, we found the caseness index for those with lifetime mania more severe than that of nonbipolar patients, with those who had hypomania being intermediate. A hierarchical analysis indicated that bipolar I tends to be diagnosed as schizoaffective-manic across occasions, and vice versa. This is consistent with the prior familial analyses that suggest these two diagnoses be combined into a single bipolar phenotype. The analysis for major depressive disorder indicates that caseness appears to represent quantitative, rather than qualitative, differences, with no natural cutoff to identify distinct subgroups. Finally, we discuss implications including utility in genetic analyses, estimation of incidence or prevalence allowing for diagnostic error, and examination of cohort effects.

Adolescent↗
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↗
PubMed1992

Risk of suicide by psychiatric diagnosis in Stockholm County. A longitudinal study of 80,970 psychiatric inpatients.

The risk of suicide associated with different psychiatric diagnoses was estimated in 80,970 inpatients in Stockholm County (population 1.6 million). All patients discharged with at least one psychiatric diagnosis between 1973 and 1986 were followed by linkage with the cause-of-death registry through 1987. There were 1,115 definite suicides and 467 undetermined suicides among these during the 15-year follow-up. When 12 diagnostic categories were entered in a proportional hazards model, the highest relative risk (RR) of definite suicide, controlling for sex and age, was noted for affective disorders (RR 2.82), followed by unspecified psychoses (RR 2.69), paranoid psychoses (RR 2.60), addiction to prescription drugs (RR 2.38), neuroses and reactive psychoses (RR 1.96), and schizophrenia (RR 1.64). Alcoholism, personality disorders, organic psychoses, and street drug addiction did not have significantly increased risks of suicide. Male sex increased the risk for definite suicide by 1.56, while the risk was somewhat higher among the young. Having more than one diagnosis increased the relative risk by 1.42. When undetermined suicides were included in the analysis, to alcoholism and street drug abuse were attributed significantly increased risks of suicide, probably owing to the greater difficulty of verifying such cases. We conclude that several psychiatric disorders were conductive to suicide, but that the risk did not vary much with the type of diagnosis. Further studies of confounders are needed, such as the reasons for being admitted to inpatient care, and the impact of somatic and psychiatric comorbidity.

Adolescent↗
PubMed1991

Current perspectives on the genetics of unipolar depression.

Evidence regarding the heritability of unipolar depression is evaluated. The data reviewed here support the involvement of genetic factors in the etiology of unipolar depression and its suitability for independent genetic inquiry, despite our inability to identify the mode(s) of transmission or identify a candidate locus. Continued progress in testing etiologic hypotheses requires (a) clarification of the mode of transmission; (b) resolution of phenotypic and potential genotypic heterogeneity; (c) general agreement on a "gold standard" for assessment of the unipolar phenotype; (d) the continued application of available quantitative methods to take into account the effects of ascertainment bias, sex effects, cohort effects, and variable/late age at onset; and (e) incorporation of quantitative indicators correlated with liability in multivariate analysis to improve the stability/validity of phenotypic determinations in segregation and linkage analysis. We present several recommendations regarding the extension of current methodologies in human population and quantitative genetics to help resolve these issues.

Chromosome Mapping↗
PubMed1991

Psychopathology and treatment of 30,344 twins in Sweden. II. Heritability estimates of psychiatric diagnosis and treatment in 12,884 twin pairs.

We estimated the heritability for inpatient psychiatric treatment, treatment with psychoactive medication, and for psychiatric diagnoses in a randomized sample of 12,884 Swedish twin pairs drawn from the general population for a health survey. We found a genetic contribution to treatment and diagnosis, independent of sex and shared environment. The heritability estimate for inpatient treatment was 0.47, for reported treatment with psychoactive medication 0.49, and for an inpatient diagnosis of neurotic or personality disorder 0.60. No statistically significant heritability was found for the diagnoses of alcohol abuse nor for the heterogeneous group of diagnoses of psychoses. This was probably because of the heterogeneity of cases necessary to form large enough groups for analysis, or ascertainment requiring treatment in a psychiatric unit.

Adolescent↗
PubMed1991

Replicated psychometric correlates of schizophrenia.

OBJECTIVE: The authors' goals are to use scales from the MMPI hypothesized in their previous research to be correlates of liability to schizophrenia to differentiate DSM-III schizophrenia from bipolar and unipolar affective illness and to cross-validate these correlates in an independently ascertained sample of patients with Research Diagnostic Criteria (RDC) schizophrenia or affective disorder. METHOD: The criterion sample consisted of 83 patients consecutively admitted to a state-operated community mental health center. Diagnosis of schizophrenia; bipolar disorder, manic; and major depression were assigned by using DSM-III. The replication sample consisted of 60 adults with RDC diagnoses of schizophrenia, schizoaffective disorder, bipolar disorder, and unipolar disorder who were parents of children in two samples collected for a study of offspring at high risk for schizophrenia and other psychopathology. After the patients in the criterion sample were classified by logistic regression analysis, the results were used to classify patients in the replication sample. RESULTS: The MMPI indicators had adequate sensitivity, specificity, and predictive power for classifying schizophrenia, and there was a moderately high rate of diagnostic agreement between the MMPI and DSM-III. Cross-validation in the replication sample was successful. Overall, the MMPI index was an adequate inclusion and exclusion criterion not only for DSM-III-defined but also for RDC-defined schizophrenia. CONCLUSIONS: A psychometric index composed of the paranoid schizophrenia, psychoticism, and manifest hostility scales from the MMPI would be a cost-effective measure to increase diagnostic efficacy in future schizophrenia research and clinical practice.

Adult↗
PubMed1990

Transmission of a psychometric indicator for liability to schizophrenia in normal families.

The genetic analysis of schizophrenia would be facilitated by identification of a heritable correlate of liability. Deviance on an index of Minnesota Multiphasic Personality Inventory (MMPI) signs is associated with the disease phenotype; the familial aggregation and mode of transmission of this continuous psychometric indicator have yet to be established. In this paper, we examine the indicator through commingling analysis and segregation analysis with both the mixed and unified models on 65 nuclear families containing 211 normal individuals. Evidence for a high degree of familiality is found. Analysis of untransformed data under a conditional likelihood provides evidence for Mendelian transmission of a major gene with commingling of two distributions. The frequency of the "high index score" allele is 0.15, with the gene accounting for 31% of the total population variance; such a locus would be relevant to the study of psychopathology as 28% of the population would carry at least one deviant allele. When power-transformed scores are used to eliminate skewness, there is evidence for one distribution and it is not possible to distinguish single gene from multifactorial (polygenic or cultural) inheritance. While our findings regarding mode of transmission must be interpreted cautiously and confirmation of a single locus requires further study, demonstration of familiality warrants continued investigation of the index as an indicator of liability for schizophrenia.

Adolescent↗
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↗
PubMed1990

Estimation of disease risk under bivariate models of multifactorial inheritance.

Adjunct consideration of both qualitative (affection status) and quantitative (correlated liability indicator) information to define a bivariate phenotype can increase considerably the accuracy and efficiency of disease risk estimation. A general approach for calculating morbid risks to offspring on the basis of parental affection status and an offspring quantitative trait is presented. We also describe two different bivariate models of multifactorial inheritance, as implemented in the computer programs POINTER and YPOINT, and make explicit their assumptions/constraints when estimating the within-person and parent-offspring correlations necessary for calculation of morbid risks. We use psychometric family data on schizophrenia from the New York High-Risk Project to estimate these correlations and illustrate our methods. Our results show that even when a trait is only moderately correlated with liability, incorporation of quantitative trait information can lead to resolution of a range of risk to offspring that is not possible through reliance on parental affection status alone. Bivariate models provide a useful methodology for incorporating quantitative indicators of liability in the investigation of genetically complex diseases.

Mathematics↗