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Biomedical subjects

G E McClearn

Publications and source records attributed to G E McClearn.

At least 55 records · Page 3Linked to original sources
PubMed1994

DNA markers associated with high versus low IQ: the IQ Quantitative Trait Loci (QTL) Project.

General cognitive ability (intelligence, often indexed by IQ scores) is one of the most highly heritable behavioral dimensions. In an attempt to identify some of the many genes (quantitative trait loci; QTL) responsible for the substantial heritability of this quantitative trait, the IQ QTL Project uses an allelic association strategy. Allelic frequencies are compared for the high and low extremes of the IQ dimension using DNA markers in or near genes that are likely to be relevant to neural functioning. Permanent cell lines have been established for low-IQ (mean IQ = 82; N = 18), middle-IQ (mean IQ = 105; N = 21), and high-IQ (mean IQ = 130; N = 24) groups and for a replication sample consisting of even more extreme low-IQ (mean IQ = 59; N = 17) and high-IQ (mean IQ = 142; N = 27) groups. Subjects are Caucasian children tested from 6 to 12 years of age. This first report of the IQ QTL Project presents allelic association results for 46 two-allele markers and for 26 comparisons for 14 multiple-allele markers. Two markers yielded significant (p < .01) allelic frequency differences between the high- and the low-IQ groups in the combined sample-a new HLA marker for a gene unique to the human species and a new brain-expressed triplet repeat marker (CTGB33). The prospects for harnessing the power of molecular genetic techniques to identify QTL for quantitative dimensions of human behavior are discussed.

Alleles↗
PubMed1994

Genetic and environmental influences on pulmonary function in aging Swedish twins.

BACKGROUND: In addition to their value in assessing pulmonary health and disease, spirometric variables have been shown to be powerful predictors of time until death in aging populations. The sources of variability in these spirometric values are consequently of relevance to basic gerontological research, and also of potential value in clinical application. The objective of this study was to estimate genetic and environmental sources of variance in pulmonary function. METHODS: The study involved 230 Swedish twin pairs (mean age = 64.9 years), of which number 37 monozygotic (MZ) pairs and 72 dizygotic (DZ) pairs had been separated and reared apart. Comparing these groups to the 57 MZ and 64 DZ pairs reared together permits stronger interpretation than that of conventional twin studies. Measures of vital capacity (VC) and forced expiratory volume in one second (FEV1) were residualized for height, age, sex, and tobacco consumption in pack-years. RESULTS: Maximum likelihood analyses of VC and FEV1 gave heritability estimates of .48 and .67, respectively. Age effects were explored both by dividing the sample into two cohorts, respectively above and below 65 years, and by moving interval analysis. In the two-cohort analysis, heritabilities were somewhat higher for the older cohort than the younger cohort for FEV1. The opposite was true for VC: heritability was lower in the older cohort, and there was evidence for a shared rearing environmental effect for this group. Moving interval analysis suggests these differences are gradual rather than saltatory. There were no gender differences in parameter estimates. CONCLUSION: Genetic factors account for between one-half and two-thirds of the variability in pulmonary function. There is a suggestion of age differences in the relative importance of genetic and environmental influences.

Adult↗
PubMed1994

Alcohol acceptance, preference, and sensitivity in mice. I. Quantitative genetic analysis using BXD recombinant inbred strains.

Although the recombinant inbred strain method was designed for molecular genetic analysis of linkage, it also provides powerful quantitative genetic analyses of heritability and genetic correlations. Measures of alcohol acceptance, alcohol preference, and hypnotic dose sensitivity (HDS) were assessed in 21 strains of mice from the BXD RI series. Sex differences were found to be significant at a phenotypic level. However, heritability estimates for acceptance, preference, and HDS are similar in males and females. Heritability estimates for the three measures are approximately 0.20 for acceptance and preference, and 0.10 for HDS. Analyses of genetic correlations reveal that acceptance and preference share some degree of genetic influence, although they mostly operate under different genetically mediated mechanisms. HDS did not show a significant genetic relationship to either acceptance or preference. Strong correlations were obtained when acceptance, preference, and HDS strain means were correlated across male and female recombinant inbreds, suggesting substantial genetic similarity across sexes.

Alcohol Drinking↗
PubMed1994

Genetic and environmental influences on blood pressure in elderly twins.

We used 289 pairs of Swedish twins reared apart or together to evaluate the importance of genetic and environmental influences on blood pressure. Unlike other twin and family studies, the adoption/twin design allows a distinction between estimates of the importance of shared rearing environments and genetic effects. Genetic factors were observed to play an important role for individual differences in blood pressure. Model-fitting analyses suggested upper limits of heritability for systolic and diastolic blood pressures in the entire sample of 0.44 and 0.34, respectively. More interestingly, substantial influences of shared family effects accounting for up to 27% of the variation were also revealed. Effects of correlated environment, which might reflect, for example, the intrauterine environment, existed to some extent later in life. The influence of genetic factors tended to decrease across age groups for systolic blood pressure (0.62 in individuals less than 65 years old; 0.12 in those 65 years and older) but not for diastolic blood pressure (0.22 for the middle-aged group; 0.26 for the older group). However, this declining trend for systolic blood pressure did not reach significance (chi 2 = 8.07, df = 4, P = .09).

Aged↗
PubMed1994

Genetic and environmental correlations among serum lipids and apolipoproteins in elderly twins reared together and apart.

Genetic and environmental correlations among five serum-lipid measures were examined in the Swedish Adoption/Twin Study of Aging. The sample included 302 twin pairs; 146 of these twin pairs were separated at an early age and were reared apart. The lipid measures examined include total cholesterol, HDL-cholesterol, triglycerides, and apolipoproteins A-I and B. Genetic and environmental correlations were evaluated for two different age groups, formed by dividing the sample at the median. The younger group included individuals 41.8-65.4 years of age at the midpoint of testing, although only 24 individuals were < 50 years of age. The older group included all those > 65.4 years of age, up to age 87 years of age. Substantial genetic correlations were found within each age group, although there is no evidence for a single genetic factor common to all five lipids. The comparison of twins reared together with twins reared apart allowed estimation of the effects of shared rearing environment; however, shared rearing environment only appears to be a significant mediator of the phenotypic correlation between apolipoprotein B and cholesterol in the older group. Examination of the genetic and environmental covariances suggests that the relative contributions of genetic factors are lower in the older group. Nonshared environmental factors are relatively more important mediators of phenotypic correlations among the serum lipids in individuals > 65.4 years of age than they are for the younger group. Sex differences in the mediation of these serum lipids were not as clear.

Adult↗
PubMed1993

Genetic and environmental influences on serum lipid levels in twins.

BACKGROUND: The extent to which serum lipid levels are affected by genetic and environmental factors remains a point of controversy. We examined both genetic and environmental influences on serum lipid levels in twins reared either together or apart who participated in the Swedish Adoption/Twin Study of Aging. METHODS: We studied 302 pairs of twins (mean age, 65.6 years; range, 52 to 86); 146 pairs had been reared apart. We simultaneously compared the twins on the basis of both zygosity and rearing status, which allowed joint estimation of genetic and environmental influences on serum lipid levels. Genetic influence was expressed in terms of heritability, the proportion of the population variation attributable to genetic variation (a value of 1.0 indicates that all of the population variation is attributable to genetic variation). The serum lipids and apolipoproteins measured included total cholesterol, high-density lipoprotein cholesterol, apolipoproteins A-I and B, and triglycerides. RESULTS: Structural-equation analyses revealed substantial heritability for the serum levels of each lipid measured, ranging from 0.28 to 0.78. Comparisons of the twins reared together with those reared apart suggested that the environment of rearing had a substantial impact on the level of total cholesterol (accounting for 0.15 to 0.36 of the total variance). Sharing the same environment appeared to affect the other lipid measures much less, however, than did genetic factors and unique environmental factors not shared by twins. Comparisons of younger with older twins suggested that heritability for apolipoprotein B and triglyceride levels decreased with age. CONCLUSIONS: The effect of genetic factors on the serum levels of some but not all lipids appears to decrease with age. Early rearing environment appears to remain an important factor in relation to levels of total cholesterol later in life, but it has less effect on other serum lipids and apolipoproteins in the elderly.

Age Factors↗
PubMed1993

Quantitative trait loci (QTL) analyses and alcohol-related behaviors.

Recombinant inbred (RI) strains can make an important contribution toward the merger of molecular genetics and quantitative genetics in the quest for quantitative trait loci (QTL). We present preliminary analyses of alcohol-related processes from our ongoing research using the BXD RI series. Issues concerning reliability, genetic correlations, and RI QTL analysis are discussed. Several strategies for replication and extension of QTL candidate regions are considered: F1 crosses between RI strains, F2 crosses, heterogeneous stock, interspecific backcrosses, QTL selection, and the use of murine QTL in chromosomal regions syntenic to human chromosomes as candidate chromosomal regions for human QTL.

Alcohol Drinking↗
PubMed1993

Genetics, systems, and alcohol.

Under a variety of rubrics (e.g., complexity, self-constructing systems, dissipative structures), interest has recently burgeoned in applying principles of complex systems to a wide variety of scientific issues. A major concern is with emergent properties of systems not derivable from the properties of components of the systems. In this paper, some elementary aspects of "systems" considerations are applied to phenomena of alcohol pharmacogenetics. It is likely that whole new families of informative phenotypes can be generated by this approach.

Alcoholism↗
PubMed1993

Heritability of irritable impulsiveness: a study of twins reared together and apart.

The heritability of self-reported personality traits related to impulsiveness, irritability, and the inhibition of assertive or aggressive behavior was examined in up to 500 healthy monozygotic and dizygotic twin pairs raised together or apart. Two factors related to "(lack of) assertiveness/aggression" (Factor I) and "impulsive irritability" (Factor II) were examined using traditional and model-fitting procedures. Results of model-fitting procedures were consistent with a genetic, but not a shared environmental, influence for both factors. Further analysis suggested a nonadditive genetic influence for Factor II and an additive influence for Factor I. Bivariate model-fitting analyses suggest that self-reported "irritable impulsiveness" and "(lack of) assertiveness/aggressiveness" show substantial, though different, genetic influences.

Adult↗
PubMed1993

Importance of genetic effects for monoamine oxidase activity in thrombocytes in twins reared apart and twins reared together.

The relative importance of shared genes, shared environments, and individual specific environmental effects for monoamine oxidase (MAO) activity in thrombocytes was assessed in the Swedish Adoption/Twin Study of Aging. The sample consists of identical twins separated at an early age and reared apart (30 pairs), identical twins reared together (60 pairs), fraternal twins reared apart (66 pairs), and fraternal twins reared together (68 pairs), whose average age was 63.5 years; 49% were female. Consistent with the literature, the heritability of MAO activity was 0.77 and did not differ across cohort (under or over 63 years of age) or gender. Sharing rearing environments or similar experiences later in life does not result in familial similarity for MAO activity.

Adoption↗
PubMed1993

Socioeconomic status and physical health, how are they related? An empirical study based on twins reared apart and twins reared together.

This investigation used the powerful combined twin and adoption design to assess the validity of three different hypotheses--social causation, childhood experiences, and health selection--on the origin of the association between socioeconomic status (SES) and health. The sample contains 99 pairs of monozygotic twins reared apart, 166 pairs of monozygotic twins reared together, 238 pairs of dizygotic twins reared apart, and 221 pairs of dizygotic twins reared together, who completed questionnaire items concerning their SES and health status. Genetic effects, environmental effects unique to the individual, as well as environmental effects shared by twins were involved in mediating the associations between SES and health. However, the relative importance of these effects varied for the different associations depending on the measures of health and SES respectively. The results indicate that social causation, childhood experiences, and health selection may all be important for the association between SES and health. It is argued that these hypotheses are not contradictory, rather the relationship between the complex dimensions SES and health may be explained by several different causes.

Adult↗
PubMed1993

Genetic and environmental effects on openness to experience, agreeableness, and conscientiousness: an adoption/twin study.

Previous research has indicated that extraversion and neuroticism are substantially affected both by genotype and environment. This study assesses genetic and environmental influences on the other three components of the five-factor model of personality: Openness to Experience, Agreeableness, and Conscientiousness. An abbreviated version of the NEO Personality Inventory (NEO-PI) was administered to 82 pairs of identical twins and 171 pairs of fraternal twins reared apart and 132 pairs of identical twins and 167 pairs of fraternal twins reared together. Estimates of genetic and environmental effects for Openness and Conscientiousness were similar to those found in other studies of personality: Genetic influence was substantial and there was little evidence of shared rearing environment. Results for Agreeableness were different: Genetic influence accounted for only 12% of the variance and shared rearing environment accounted for 21% of the variance. Few significant gender or age differences for genetic and environmental parameters were found in model-fitting analyses.

Adoption↗
PubMed1993

Use of twin cohorts for research in Alzheimer's disease.

The causes of Alzheimer's disease (AD) remain a mystery despite the recent identification of several putative environmental risk factors and the discovery of several linked genetic loci and point mutations associated with the disease. Particularly uncertain is the generalizability of the genetic findings to the common forms of disease encountered in clinical practice or population research. Twin studies of AD can illuminate causal mechanisms, both genetic and environmental. This consensus document explores the rationale for such twin studies, as well as a number of methodologic problems that render them difficult to implement or interpret. We review existing twin studies of AD and note several ambitious new studies. Finally, we delineate several practical strategies for the near future of twin research in AD.

Aged↗
PubMed1993

The utilization of quantitative trait loci in toxicogenetics.

With the increasing number of marker loci available in mouse, the traditional method of recombinant inbred strains can be extended to searches for quantitative trait loci (QTL) influencing continuously distributed phenotypes. These loci have effect sizes too small to be easily detectable by conventional single-locus techniques. Collective, several QTL may account for a substantial proportion of the phenotypic variability. Prospective advantages of location of QTL in toxicology-relevant phenotypes include opportunities for the study of mechanism, prospects of generating animal models by genotypic selection, study of the dynamics of gene interaction, and guiding the search for homologous genes in human beings.

Alleles↗
PubMed1992

The reliability and stability of biomarkers of aging.

Different types of stability of a biomarker are important properties, influencing the degree of predictability across age (ordinal stability) and the interpretation of quantitative and qualitative change with age (structural stability). These properties may be expected to differ from biomarker to biomarker and may change with age. Any age-related process with individual differences in time of onset of change or in rate of change will necessarily display reduced ordinal stability. Another source of reduced correlation across occasions is the short-term fluctuance of individuals due to cyclic processes and to responsiveness to environmental displacements of biomarker values and recovery therefrom. Structural stability of composite variates may be quite high across relatively short intervals but sufficiently low across longer intervals as to suggest the inappropriateness of simple description of mean changes or differences across these longer time spans. The outcome with multivariate composites raises the issue that single biomarkers may have quite different meanings at different parts of the life span.

Aging↗
PubMed1992

Single-locus control of saccharin intake in BXD/Ty recombinant inbred (RI) mice: some methodological implications for RI strain analysis.

The sac locus, with a major effect on saccharin preference, was discovered by Fuller (1974) in C57BL/6J (B6), DBA/2J (D2), and derived crosses, and is now supported in the BXD/Ty recombinant inbred (RI) series by a marked bimodal distribution in saccharin preference among 20 strains. The B6 allele led to increased saccharin preference compared to the D2 allele. Since the search for bimodal distributions reflecting major gene loci is an essential part of RI strain analysis, a new statistical method is proposed to test for bimodality, and comparisons are made to previously proposed methods. Another new RI method, quantitative trait loci (QTL) analysis, allows provisional detection and mapping of minor as well as major gene loci. Using this method as a screen, significant associations with saccharin preference were suggested with marker loci on portions of six chromosomes. One of these, the D12nyu1 locus on chromosome 12, was independently supported in a panel of standard (non-RI) inbred strains also tested for saccharin preference. It is unclear whether this reflects the sac locus.

Animals↗
PubMed1992

The use of CXB recombinant inbred mice to detect quantitative trait loci in behavior.

Although recombinant inbred (RI) series of mice have been developed to identify and map single-gene characteristics, they can also be used to identify quantitative trait loci (QTL) that account for small amounts of variance in quantitative traits such as behavior. We applied an RI QTL approach to the analysis of published behavioral data from seven studies that used the CXB RI series of mice. Nearly all of the behaviors showed strain distribution patterns indicative of multiple-gene rather than single-gene influence. Although the CXB series is limited to seven RI strains, RI QTL association analysis suggests QTL candidate markers for several behaviors, including avoidance and exploration.

Animals↗