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Biomedical subjects

M McGue

Publications and source records attributed to M McGue.

At least 19 recordsLinked to original sources
PubMed1992

Genetic and environmental influences on baseline SCE.

Previous population-based studies have identified subject characteristics that, when combined, can account for approximately 20% of the observed interindividual variation in baseline SCE rates. In the present investigation, a classic twin study design was used to address the issue of the relevance of genetic factors to baseline SCE rates and to identify other demographic, hematologic, and exposure variables predictive of SCE rate. Questionnaire data and peripheral blood samples from 136 monozygotic and 88 dizygotic twins (age range: 25-81 years) were obtained. Among the large number of variables examined, univariate analyses (including ANOVA tests for the categorical variables and Pearson-product moment correlations for the quantitative variables) revealed smoking status, coffee drinking status, sex, white blood cell count, and absolute numbers of lymphocytes and neutrophils to have significant effects on SCE rates. A stepwise multiple regression analysis showed that together, smoking and coffee drinking status entered at the first step accounted for 21% of the observed variance in SCE, with a further 6% being contributed by the demographic and hematologic variables added in subsequent steps. Finally, the twin analyses showed that after adjustment of the data set for smoking and other significant predictors, genetic factors accounted for approximately 30% of the variation in SCE rates. Thus these data support the hypothesis of a significant genetic influence on baseline SCE.

Environment↗
PubMed1992

Emergenesis. Genetic traits that may not run in families.

Traits that are influenced by a configuration--rather than by a simple sum--of polymorphic genes may not be seen to be genetic unless one studies monozygotic twins (who share all their genes and thus all gene configurations) because such "emergenic" traits will tend not to run in families. Personal idiosyncrasies that have been found to be surprisingly concordant among MZ twins separated in infancy and reared apart may be emergenic traits. More speculatively, important human traits like leadership, genius in its many manifestations, being an effective therapist or parent, as well as certain psychopathological syndromes may also be emergenic. These ideas reemphasize the importance of the role played in human affairs by genetic variation.

Adult↗
PubMed1992

Sex and age effects on the inheritance of alcohol problems: a twin study.

Male monozygotic cotwins of probands with Alcohol Abuse-Dependence (n = 85) were more likely than male same-sex dizygotic cotwins (n = 96) to report alcohol, drug, and conduct disorder problems. For women, rates of problem behavior did not differ between monozygotic (n = 44) and same-sex dizygotic (n = 43) cotwins. Opposite-sex dizygotic twin data (n = 88) revealed significant cross-sex transmission; alcohol problems were greatest among male cotwins of female probands. For men, proportion of liability variance associated with additive genetic factors was significantly greater when proband had an early (h2 = .73 +/- .18) rather than late (h2 = .30 +/- .26) age of onset. For women, heritability did not vary as a function of proband's age of onset, and the pooled estimate suggested little genetic influence (h2 = .00, SE not computable). Findings suggest that genetic influences may be substantial only in the etiology of early-onset male alcoholism.

Adult↗
PubMed1992

A 28-year follow-up of adults with a history of moderate phonological disorder: linguistic and personality results.

The present investigation is a follow-up to a longitudinal speech and academic study involving approximately 400 normally developing children begun in 1960 by Mildred Templin. From this large data base, the present project invited the participation of two groups of subjects (now aged 32 to 34): (a) 24 adults with a documented history of moderately severe phonological disorder that persisted at least through the end of first grade (probands) and (b) 28 adults from the same birth cohort and schools who were known to have had at least average articulation skills over the same period (controls). Results of follow-up testing revealed that the proband adults performed significantly more poorly than the control adults on all of the administered measures of articulation, expressive language, and receptive language. Results obtained from a screening of nonverbal reasoning ability were equivocal. On a questionnaire measure of personality, both groups scored well within the normal range for the dimensions of extroversion and neuroticism when compared to the test's normative sample. These results have been interpreted as suggesting that although many adults with a childhood history of delayed phonological development will continue to experience linguistic outcomes that are less favorable than those of controls, their performance in selected nonlanguage domains (e.g., nonverbal reasoning, personality) will be far more typical of the general population.

Adult↗
PubMed1992

When assessing twin concordance, use the probandwise not the pairwise rate.

Geneticists and twin researchers have long debated the relative merits of two alternative measures of twin concordance: the pairwise and probandwise concordance rates. The results of this debate are now quite clear, for almost every application the probandwise rate is preferred over the pairwise rate. In a recent review of schizophrenia twin studies, however, Torrey (1992) chose to analyze pairwise rather than probandwise rates. Torrey's use of pairwise rates led him to conclude that the monozygotic twin concordance for schizophrenia is weaker than what is widely accepted, and that, by implication, the magnitude of the genetic contribution to schizophrenia has been overestimated. In this brief commentary, we review the relative strengths and weaknesses of the pairwise and probandwise rates and show that Torrey's conclusion is based upon his incorrect use of pairwise rates. Twin studies of schizophrenia continue to support the existence of a strong genetic influence on the development of schizophrenia.

Female↗
PubMed1991

Heterogeneity in the inheritance of alcoholism. A study of male and female twins.

Genetic influence on risk for alcoholism was examined in a US treatment sample of 50 monozygotic (MZ) and 64 dizygotic (DZ) male and 31 MZ and 24 DZ female same-sex twin pairs. For the DSM-III composite diagnosis of Alcohol Abuse and/or Dependence, statistically significant MZ/DZ differences in concordance were found with male, but not female, twins. For specific diagnoses, MZ/DZ differences were found in male subjects for both Alcohol Abuse and Alcohol Dependence, while MZ/DZ differences in female subjects were found only for Alcohol Dependence. The male MZ/DZ concordance difference for composite diagnosis but not for Alcohol Dependence could be accounted for statistically by differences in age of onset between MZ and DZ probands. As with alcohol, differences in MZ/DZ concordance were found for DSM-III composite diagnoses of Other Substance Abuse and/or Dependence with male, but not female, twins. Using Epidemiological Catchment Area data to estimate the population base rates of both alcohol and other substance use disorders allowed for heritability analyses that showed genetic factors to have only a modest influence on overall risk in both sexes (heritability estimates of approximately 0.35 for male subjects and 0.24 for female subjects). However, evidence for heterogeneity in the pattern of inheritance was also found, suggesting forms of alcoholism that may be moderately to highly heritable.

Age Factors↗
PubMed1991

The genetic epidemiology of schizophrenia and the design of linkage studies.

There are three aspects of schizophrenia that are challenges to the design of linkage studies. First, analysis of twin and family data have consistently failed to identify a single major gene effect. Second, ascertainment of multiplex families does not guarantee the sampling of families in whom a major gene is segregating even if such a gene exists. Third, environmental influences appear to play an essential role in the etiology of at least some schizophrenia. The implications of these features for linkage strategies in schizophrenia are discussed.

Cross-Sectional Studies↗
PubMed1991

Atopic disease and immunoglobulin E in twins reared apart and together.

Both genetic and environmental influences have been implicated in the etiology of atopic disease and in the determination of serum IgE levels. To quantify the relative contribution of these influences, we studied the prevalence of asthma and seasonal rhinitis, skin-test response, total serum IgE levels, and specific IgE, as measured by RAST, in a sample of MZ and DZ twins reared apart or together. Concordance rates for asthma, rhinitis, positive skin tests, and RAST were calculated. MZ twins, whether reared apart or together, showed a greater concordance than dizygotic twins reared apart or together. Maximum-likelihood tests of genetic and environmental components of the variation of total IgE levels revealed a substantial genetic component and a negligible contribution from common familial environmental effects.

Asthma↗
PubMed1990

Sources of human psychological differences: the Minnesota Study of Twins Reared Apart.

Since 1979, a continuing study of monozygotic and dizygotic twins, separated in infancy and reared apart, has subjected more than 100 sets of reared-apart twins or triplets to a week of intensive psychological and physiological assessment. Like the prior, smaller studies of monozygotic twins reared apart, about 70% of the variance in IQ was found to be associated with genetic variation. On multiple measures of personality and temperament, occupational and leisure-time interests, and social attitudes, monozygotic twins reared apart are about as similar as are monozygotic twins reared together. These findings extend and support those from numerous other twin, family, and adoption studies. It is a plausible hypothesis that genetic differences affect psychological differences largely indirectly, by influencing the effective environment of the developing child. This evidence for the strong heritability of most psychological traits, sensibly construed, does not detract from the value or importance of parenting, education, and other propaedeutic interventions.

Adult↗
PubMed1990

Does contact lead to similarity or similarity to contact?

Evidence from the Finnish Twin Registry (e.g., Rose et al., 1988) shows that adult monozygotic (MZ) twins are more similar, within pairs, in personality if the cotwins are presently cohabiting or in frequent contact than if they are seldom in contact. Results of a follow-up study led Kaprio et al. (1990) to conclude that "changes in social contact between monozygotic cotwins precede (and causally contribute to) changes in their intrapair similarity" (p. 9). If true, this conclusion has important theoretical implications, e.g., many heritability estimates would have to be revised downward. We adduce evidence suggesting that similarity leads to contact, rather than the other way around. Low correlations between twins' frequency of contact and their absolute within-pair difference on all traits thus far studied indicates that, whichever the direction of causality, the relationship between MZ within-pair similarity and their frequency of contact is very weak.

Adult↗
PubMed1990

The Minnesota Twin Family Registry: some initial findings.

A birth-record based Registry is nearing completion of some 8,000 pairs of twins born in Minnesota from 1936 to 1955, plus some 1,200 pairs of male twins born 1971-81. The middle-aged twins were recruited with graded incentives so that ease of recruitment could be measured; it was found that pairs concordant for ease of recruitment were no more similar than discordant pairs in education, socioeconomic status (SES), or a variety of personality and interest factors, ie, that selection bias may not be a problem in research with adult twins when contacts are only by mail. A 50% decrease in neonatal mortality from 1936-55 to 1971-81 was associated with an increase from 3.5 to 4.0 per thousand in the frequency of viable MZ twin births. The broad heritability of SES, educational attainment, fecundity, and risk for divorce ranges from 0.30 to 0.50, although all 4 variables are plainly multifactorial and the latter 2 both involve variance contributed by a second person. Investigators interested in making use of this research resource are invited to submit proposals.

Anthropometry↗
PubMed1990

Sex-linked determinants for IgM?

Evidence for a sex-linked determinant of immunoglobulin M levels was sought using correlational and commingling analyses in a sample of 174 randomly selected nuclear families. While mean IgM levels in females were approximately 25% higher than that in males, the pattern of familial correlations did not follow the expectations under a sex-linked model, and there was no commingling in the distribution of IgM levels as expected when a trait is under the influence of a major gene.

Canada↗
PubMed1989

Path analysis under generalized marital resemblance: evaluation of the assumptions underlying the mixed homogamy model by the Monte Carlo method.

Path analysis of nuclear family data has been widely applied to resolve genetic and environmental sources of familial resemblance. Here we report the results of a systematic evaluation of the effects of departures from five modeling assumptions often made when analyzing nuclear family data; i) the observed environmental index is unaffected by the genotype, ii) the basis of marital resemblance is correctly specified in the model, iii) there are no intergenerational differences in either the genetic or cultural heritability, iv) there is no genetic dominance, and v) there is no genotype by family environment interaction. "Deterministic simulations" identified various situations where model misspecification could lead to substantial bias in the estimation of the heritabilities. For these situations, "stochastic simulations" were performed to determine whether the "goodness-of-fit" test used in path analysis would correctly reject the misspecified model. In samples of 500 nuclear families, each comprising two parents and two children, the goodness-of-fit test was found to be sensitive to misspecifications of the source of marital resemblance and the existence of intergenerational differences in heritabilities, although reduced power would make the test less sensitive in smaller samples. The test was largely insensitive to misspecifications of possible genetic effects on the environmental index, and to the existence of multiplicative interaction between the genotype and familial environment. When genetic effects on the index are ignored, the genetic heritability (h2) is underestimated, the cultural heritability (c2) is overestimated, but h2+c2 remains unchanged. Neglecting the interaction was found to result in an overestimate of h2.

Consanguinity↗
PubMed1989

Genetic linkage in schizophrenia: perspectives from genetic epidemiology.

Research on the genetic epidemiology of schizophrenia is briefly and selectively reviewed. The following three salient features of schizophrenia that represent challenges to the design of linkage studies are identified: (1) The analysis of twin and family data has consistently failed to identify a single major gene effect upon schizophrenia risk; (2) the ascertainment of multiplex families does not guarantee the sampling of families who are segregating for the major gene even if a major gene effect exists; and (3) environmental influences appear to play an essential role in the etiology of at least some forms of schizophrenia. The implications of these features for the design of linkage studies in schizophrenia are discussed.

Diseases in Twins↗
PubMed1989

Commingling in the distributions of immunoglobulin levels.

Commingling in the distributions of five immunoglobulins from a Canadian sample of 810 Caucasians and IgE from a US sample of 935 Caucasians was investigated. For both the Canadian and US samples significant commingling was found in the child's but not the adult's IgE distribution. Contrary to expectations based upon the major gene hypothesis for IgM, we found no evidence for commingling in the IgM distribution. Finally, the distributions of IgA, IgD and IgG all evidenced significant commingling that may be the result of a single gene effect or the operation of a discrete environmental effect.

Adult↗