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Biomedical subjects

L A Corey

Publications and source records attributed to L A Corey.

At least 19 recordsLinked to original sources
PubMed2001

Irritable bowel syndrome in twins: heredity and social learning both contribute to etiology.

BACKGROUND & AIMS: Heredity has been suggested to explain the finding that irritable bowel syndrome (IBS) tends to run in families. Research in this area has been limited. The aim of the present study was to assess the relative contribution of genetic and environmental (social learning) influences on the development of IBS by comparing concordance rates in monozygotic and dizygotic twins to concordance between mothers and their children. METHODS: Questionnaires soliciting information on the occurrence of more than 80 health problems, including IBS, in self and other family members were sent to both members of 11,986 twin pairs. RESULTS: Analysis is based on 10,699 respondents representing 6060 twin pairs. Concordance for IBS was significantly greater (P = 0.030) in monozygotic (17.2%) than in dizygotic (8.4%) twins, supporting a genetic contribution to IBS. However, the proportion of dizygotic twins with IBS who have mothers with IBS (15.2%) was greater than the proportion of dizygotic twins with IBS who have co-twins with IBS (6.7%, P < 0.001), and logistic regression analysis showed that having a mother with IBS and having a father with IBS are independent predictors of irritable bowel status (P < 0.001); both are stronger predictors than having a twin with IBS. Addition of information about the other twin accounted for little additional predictive power. CONCLUSIONS: Heredity contributes to development of IBS, but social learning (what an individual learns from those in his or her environment) has an equal or greater influence.

Adult↗
PubMed1999

A multivariate genetic analysis of the use of tobacco, alcohol, and caffeine in a population based sample of male and female twins.

Numerous epidemiologic studies in the past few decades have consistently demonstrated positive associations between the use of various psychoactive substances, both licit and illicit. This association could be due to shared genetic and/or shared environmental risk factors. This study uses multivariate structural equation modeling to determine the sources of covariation between the use of tobacco, alcohol, and caffeine, the three most commonly consumed psychoactive substances. In particular, we wish to clarify the extent to which genetic and environmental risk factors are shared across these three substances versus are substance specific in their effect. The sample, consisting of data collected from members of the population-based Virginia Twin Registry, consists of 774 monozygotic and 809 dizygotic male and female twin pairs. Our results demonstrate that genetic and individual specific environmental factors that are shared between these three substances account for a modest proportion of the total variance. For example, shared genetic risk factors across the three substances in males and females account for between 7 and 28% of the total variance in liability and 12-56% of the genetic variance. Common familial environment appears to play little or no role. Underlying genetic and individual environmental risk factors produce liability to (poly)substance use in general; substance specific factors also play an important etiologic role.

Adult↗
PubMed1999

Epilepsy and seizure occurrence in a population-based sample of Virginian twins and their families.

Epilepsy and seizure occurrence was assessed in a large, population-based sample of Virginian twins and their families. Medical history information on twins and their relatives was collected by questionnaire and used to estimate prevalence of seizures and epilepsy for this sample. Health history information was available on 16,634 twins and their families. Lifetime prevalence of a history of seizures ranged from < 1 to 5%. Concordance rates were larger in monozygotic (MZ) than dizygotic (DZ) pairs overall, however, significant differences between the zygosities were only noted for Caucasian twins. To facilitate interpretation of results, the sample was partitioned into two age groups: 16-35 years and > 35 years of age. In the first age category of twins, significant differences were observed for the following seizure types; epilepsy (0.30 and 0.13, p <0.03), febrile seizures (0.39 and 0.12, p <0.001), and other convulsions/seizures (0.28 and 0.01, p < 0.001). While for twins in the second age category, only the comparison for febrile seizures (0.42 and 0.14, p < 0.001) resulted in a significant difference between zygosities. A family history of seizures was reported in 215 (35.1%) of the 613 seizure positive probands. Increased risk of seizures (1.88-4.64) among relatives of affected versus unaffected individuals was also observed.

Adolescent↗
PubMed1999

A population-based twin study in women of smoking initiation and nicotine dependence.

BACKGROUND: The development of drug dependence requires prior initiation. What is the relationship between the risk factors for initiation and dependence? METHODS: Using smoking as a model addiction, we assessed smoking initiation (SI) and nicotine dependence (ND) by personal interview in 1898 female twins from the population-based Virginia Twin Registry. We developed a twin structural equation model that estimates the correlation between the liability to SI and the liability to ND, given SI. RESULTS: The liabilities to SI and ND were substantially correlated but not identical. Heritable factors played an important aetiological role in SI and in ND. While the majority of genetic risk factors for ND were shared with SI, a distinct set of familial factors, which were probably partly genetic, solely influenced the risk for ND. SI was associated with low levels of education and religiosity, high levels of neuroticism and extroversion and a history of a wide range of psychiatric disorders. ND was associated with low levels of education, extroversion, mastery, and self-esteem, high levels of neuroticism and dependency and a history of mood and alcohol use disorders. CONCLUSIONS: The aetiological factors that influence SI and ND, while overlapping, are not perfectly correlated. One set of genetic factors plays a significant aetiological role in both SI and ND, while another set of familial factors, probably in part genetic, solely influences ND. Some risk factors for SI and ND impact similarly on both stages, some act at only one stage and others impact differently and even in opposite directions at the two stages. The pathway to substance dependence is complex and involves multiple genetic and environmental risk factors.

Adult↗
PubMed1999

Genetic and environmental risk factors in the aetiology of illicit drug initiation and subsequent misuse in women.

BACKGROUND: Subsequent to initial exposure to the use of a psychoactive substance, psychoactive substance use disorder (PSUD) may or may not develop. AIMS: To investigate the relationship between the risk factors for initiation and the subsequent misuse of psychoactive substances. METHOD: The lifetime history of illicit substance use and misuse was obtained by telephone interview with 1934 members of female-female twin pairs. We apply a novel model, which estimates the role of genetic and environmental risk factors that influence initiation and those specific to misuse, to three classes of illicit psychoactive substances. RESULTS: The individual-specific environment and family environment influenced the probability of initiation, but only individual-specific environment had an impact on the probability of subsequent misuse. Genetic factors which influence the risk of initiation and of misuse were identified. CONCLUSIONS: Aetiological factors that influence drug initiation and subsequent misuse are correlated but not identical. Family environment is an important determinant of risk for drug experimentation. Two classes of genetic risk factors act on the liability to PSUD: those that influence the probability of initiation and those that influence the risk of misuse.

Adult↗
PubMed1998

Univariate genetic analyses of epilepsy and seizures in a population-based twin study: the Virginia Twin Registry.

The purpose of this study was to examine the roles of genetic and environmental factors in the etiology of epilepsy and seizures in twins ascertained from the Virginia Twin Registry. Health history information on twins was collected by questionnaire. Concordance rates were calculated and used to estimate degree of concordance for seizure types in monozygotic (MZ) and dizygotic (DZ) twin pairs. Univariate twin analyses were performed for each epilepsy and seizure type to determine models which best explained observed variation. Health history information concerning epilepsy and febrile seizure occurrences was provided by members of 8,655 twin pairs; 6,684 of these supplied additional information reporting absence, complex partial, tonic-clonic, and unspecified seizures. Models including additive genetic and unique environmental factors best explained febrile seizures, epilepsy, complex partial seizures, and unspecified seizures. For complex partial seizures, however, the contributions of genetic and environmental effects did not vary across gender. These results show that, under univariate analysis methods, genetic factors played an important role in the expression of seizures in epilepsy, febrile seizures, unspecified seizures, and complex partial seizures. Additional support for these findings was provided by the concordance results for all categories except male twins reporting complex partial seizure occurrence. However, environmental influences still remained an important factor in seizure expression in these specific categories.

Adolescent↗
PubMed1998

Longitudinal population-based twin study of retrospectively reported premenstrual symptoms and lifetime major depression.

OBJECTIVE: While family and twin studies suggest that retrospectively reported premenstrual symptoms are heritable, these studies have not accounted for the unreliability of such measures. In addition, we know little about the relationship of the familial risk factors for premenstrual symptoms and major depression. METHOD: Lifetime major depression and premenstrual-related tiredness, sadness, and irritability were assessed twice over 6 years in 1,312 menstruating female twins ascertained from a population-based twin register. A twin-measurement model--which permits estimation of the etiologic roles of genetic and environmental factors with correction for errors of measurement or short-term temporal fluctuations--was applied to these data. RESULTS: A single premenstrual symptom factor was found that was moderately stable over time. The best-fitting twin-measurement model estimated the heritability of the stable component of premenstrual symptoms at 56% and showed no impact of family-environmental factors. A bivariate twin-measurement model estimated that the genetic and environmental risk factors for lifetime major depression contributed only modestly to the etiology of premenstrual syndrome. No evidence was found for significant biases in the twin method. CONCLUSIONS: Retrospectively reported premenstrual-related symptoms of depression and anxiety are moderately stable over time and, when correction is made for this level of stability, substantially heritable. The genetic and environmental risk factors for these premenstrual symptoms and lifetime major depression are not closely related.

Adult↗
PubMed1998

Evidence for a genetic predisposition for status epilepticus.

The role of genetic factors in determining risk for status epilepticus (SE) was examined in twins identified using the population-based Virginia Twin Registry. Concordance rates for SE were 0.38 for monozygotic (MZ) and 0.00 for dizygotic (DZ) twins, with the rate in MZs being significantly increased over DZs. The prevalence of SE in MZ co-twins of affected individuals was as high as 0.55. Clinical presentation of SE was evaluated, and no association was found between occurrence of SE and age at onset or seizure etiology. Genetic factors contribute to risk for SE.

Disease Susceptibility↗
PubMed1997

Predictors of problem drinking and alcohol dependence in a population-based sample of female twins.

OBJECTIVE: To identify characteristics associated with problem drinking (PD) and alcohol dependence (AD) in women. METHOD: Subjects were 2,163 white women aged 17-55 from the population-based Virginia Twin Registry. Measures were selected from a clinical interview and questionnaires to reflect five domains associated with alcoholism in prior studies; demographic characteristics, personality, health, and personal and family history of psychopathology. Logistic and linear regression analyses were used to predict PD and DSM-III-R defined AD. RESULTS: Multiple regression models accounted for 19% of the variance in PD (significant predictors included: higher parental education-particularly among younger women, being the primary breadwinner, less frequent church attendance, higher scores on measures of neuroticism, extraversion and interpersonal dependency, history of major depression and social phobia, paternal PD and maternal treatment for emotional problems); 9% of the variance in diagnosis of AD (predicted by generalized anxiety, paternal depression and maternal PD); and 20% of the variance in number of symptoms of AD (predicted by the interaction of younger age and less-educated parents, higher neuroticism and mastery, lower optimism, generalized anxiety and agoraphobia, and maternal PD). CONCLUSIONS: Personality characteristics and parental psychopathology are important predictors of PD and AD independent of their effect on risk for affective and anxiety disorders. Many characteristics found to be associated with PD and AD in bivariate analyses were not significant when considered in the context of other predictors. Future studies of the etiology of alcoholism among women should simultaneously study measures from a variety of domains.

Adolescent↗
PubMed1996

Childhood parental loss and alcoholism in women: a causal analysis using a twin-family design.

Childhood parental loss may be an important risk factor for psychiatric illness in adulthood. While this association has been carefully examined for depression, little is known about the role of parental loss in predisposing to alcoholism. We examined an epidemiological sample of female twin pairs with the same history of continuity or disruption in parent-child relationships (N=1018 pairs; mean age 30 years), using a range of definitions of alcoholism. Childhood parental loss through separation, but not death, substantially increased the risk in adulthood for all definitions of alcoholism. Furthermore, both paternal and maternal alcoholism substantially increased the probability of parental separation from their children. Proposing a structural equation twin-family model that incorporates childhood parental loss as a specified environmental risk factor, we examined how much of the association between childhood parental loss and alcoholism was causal (i.e. mediated by environmental factors) v. non-causal (mediated by genetic factors, with parental loss serving as an index of parental genetic susceptibility to alcoholism). Both the causal and non-causal paths were significant for all definitions of alcoholism. However, the causal-environmental pathway consistently accounted for most of the association. While a significant proportion of the association is due to non-causal genetic mechanisms, childhood parental loss (or the familial discord that precedes or follows it) is probably a direct and significant environmental risk factor for the development of alcoholism in women.

Adult↗
PubMed1993

Common fragile site expression in lymphocytes from an individual mosaic for trisomy 8.

During the course of a survey of fragile site expression in lymphocytes from twins one member of a dizygotic pair was found to be mosaic for trisomy 8. One hundred fifty metaphases from this individual were analyzed (100 treated with aphidicolin and 50 untreated); 43% were 46,XY and 57% 46,XY,+8. No differences were observed between the treated and control cultures in either the proportions of normal and trisomic metaphases or the overall or specific fragile site expression in the normal and trisomic cells.

Adolescent↗
PubMed1993

Self-reported periodontal disease in a Virginia twin population.

To investigate the contribution of genetic factors in the etiology of periodontal disease, questionnaire data were collected on 4,908 twin pairs included in the population-based Virginia Twin Registry. A history of periodontal disease was reported in 420 individuals who were members of 116 monozygotic (MZ) and 233 dizygotic (DZ) twin pairs. The mean age at diagnosis in this sample was 31.4 +/- 0.7 years and was significantly earlier in females than males (30.1 vs. 33.0 years, P < 0.025). Proband-wise concordance rates were 0.38 for MZ and 0.16 for DZ twins. There were no differences in concordance rate between same and opposite-sexed dizygotic twins. These findings provide evidence that genetic factors make an important contribution to risk for adult-onset periodontal disease.

Adult↗
PubMed1992

The epidemiology of pregnancy complications and outcome in a Norwegian twin population.

OBJECTIVE: To measure the contribution of genetic factors to selected pregnancy complications, including miscarriage, twinning, hypertension-toxemia, and nausea-vomiting. METHODS: Information on 22,241 pregnancies of 8675 female twins or spouses of male twins was obtained by questionnaire from members of the population-based Norwegian Twin Panel. Comparisons of observed tetrachoric correlations were used to assess the importance of genetic influences on the variables examined. RESULTS: Pregnancy history information was provided by both members of 830 monozygotic and 902 dizygotic female twin pairs and by the spouses of both members of 459 monozygotic and 464 dizygotic male twin pairs. The incidence of twin pregnancy in general, and of opposite-sexed twins in particular, found among dizygotic twin women was nearly twice that observed for any other group. Monozygotic female twin pairs were more concordant than dizygotic female twin pairs for the occurrence of miscarriage, nausea or vomiting during pregnancy, and hypertension or overt toxemia. A similar pattern of twin similarity was observed for the use of certain medications during pregnancy including vitamins, aspirin, and nausea medication. CONCLUSIONS: Maternal genetic factors make an important contribution to a predisposition for dizygotic twinning, contribute to the risk of miscarriage, and appear to determine, in part, whether a woman experiences nausea-vomiting or hypertension-toxemia during pregnancy. In addition, health-seeking behaviors of women during pregnancy, as reflected by the use of several classes of medication, appear to be influenced somewhat by genetic factors.

Female↗
PubMed1992

Aphidicolin-inducible common fragile-site expression: results from a population survey of twins.

Common chromosomal fragile sites appear to be ubiquitous in humans and other mammals, and, although the molecular basis and function of these sites remain an enigma, it has been speculated that they may be a cytogenetic expression of gene activity. A population survey of 28 twin pairs was conducted to assess the heritability of common fragile-site expression. Our data yielded a heritability estimate of .88 for total site expression, suggesting that these sites may result from some common process that is under relatively stringent genetic control. An analysis of the expression of individual autosomal sites revealed that expression on both homologues in the same cell occurred more frequently than expected.

Adolescent↗
PubMed1991

The occurrence of epilepsy and febrile seizures in Virginian and Norwegian twins.

Twin studies provide an efficient method for examining the importance of genetic and environmental factors in the etiology of disorders such as epilepsy. Population-based twin registries are especially valuable for studies of this type since effects of reporting and self-selection biases on the resulting data are minimized. Among 14,352 twin pairs contained in the Virginia and Norwegian twin panels for whom questionnaire information was available, there was a history of epilepsy in one or both members of 286 pairs; febrile seizures were reported in 257 pairs. Analyses of questionnaire data revealed no significant differences in concordance rates between Virginian and Norwegian twins for either epilepsy or febrile seizures. Probandwise concordance rates for epilepsy were 0.19 in monozygotic twins and 0.07 in dizygotic twins. Analogous rates for febrile seizures were 0.33 (monozygotic) and 0.11 (dizygotic). These results provide further evidence that genetic factors do have a role in the expression of epilepsy and febrile seizures.

Diseases in Twins↗
PubMed1990

Histopathology of endocervical infection caused by Chlamydia trachomatis, herpes simplex virus, Trichomonas vaginalis, and Neisseria gonorrhoeae.

We determined the histologic correlates of clinically identified mucopurulent cervicitis, culture-proven cervical infection with Chlamydia trachomatis, Neisseria gonorrhoeae, herpes simplex virus (HSV), and vaginal infection with Trichomonas vaginalis by examining cervical biopsies from 83 women. Clinical mucopurulent cervicitis and culture-documented infection with one or more of these pathogens correlated histologically with intraepithelial neutrophils, reactive endocervical cells, edema, luminal neutrophils, and with several deeper tissue changes such as extensive and dense subepithelial inflammation, granulation tissue, and necrotic ulceration. Focal loss of surface columnar cells and spongiosis were also correlated with culture-confirmed infection. Well-formed germinal centers were seen in biopsies from 14 of 21 patients (67%) with C trachomatis infection alone, but in none of 17 patients with infections other than C trachomatis (P less than 0.001). A predominantly plasmacytic infiltrate was also significantly associated with chlamydial infection. Necrotic ulcers overlying a predominantly lymphocytic infiltrate were seen in six of nine patients (67%) with HSV infection alone but in only two of 40 patients (5%) with other infections (P less than 0.001). Marked inflammatory changes were not seen in the patients infected with N gonorrhoeae. The organism T vaginalis was not associated with any endocervical pathology. If these results are confirmed by prospective studies, they suggest that pathologists should alert clinicians to the possibility of recent or current infection with C trachomatis or HSV when cervical biopsies show the above changes. The loss of surface columnar epithelium with HSV, chlamydial, and gonococcal infection offers a possible explanation for the reported association of these infections with increased risk of acquiring human immunodeficiency virus infection.

Adolescent↗