Biomedical subjects

J C Christian

Publications and source records attributed to J C Christian.

At least 37 records · Page 2Linked to original sources

PubMed1996

Saccadic characteristics of monozygotic and dizygotic twins before and after alcohol administration.

PURPOSE: To evaluate the degree of heritability in the latency, accuracy, and peak velocity of reflexive saccades in young adult monozygotic (MZ) and dizygotic (DZ) twins before and after the administration of a single dose of ethanol. METHODS: Saccades were recorded using a scleral search coil before and after alcohol consumption, and data were analyzed offline. Estimates of heritability based in intraclass correlations (ICCs) and using a maximum likelihood estimates of genetic variance were calculated for the saccadic measures made before and after alcohol, as well as for the changes in latency, accuracy, and velocity. RESULTS: Intraclass correlations for MZ twins (rMZ) were highly significant; those for DZ twins (rDZ) were not significantly different from zero. This disparity between rMZ and rDZ suggests either multiple gene interactions or in utero environmental differences in the MZ twins. Alcohol significantly prolonged latency, reduced accuracy, and lowered peak velocity. Although the changes after alcohol were not significant, heritability values increased in all three measures after alcohol administration. CONCLUSIONS: Latency, accuracy, and peak velocity appear to be controlled by multiple genes or to depend on prenatal environmental factors. Even a single low dose of alcohol appeared to enhance heritability measures. Differences seen between ICCs for latency, accuracy, and velocity after alcohol administration suggest that developmental control of the neural mechanisms underlying each measure may vary.

Adult↗

PubMed1995

Cognitive scores in carriers of Huntington's disease gene compared to noncarriers.

Huntington's disease (HD) is a progressive neurodegenerative disorder recently shown to be due to an excess number of CAG trinucleotide repeats in the 5' translated region of chromosome 4. One of the cardinal features of HD is cognitive decline. While mental deterioration is obvious later in the disease course, the time of its onset is difficult to determine precisely. A sample of at-risk individuals without signs or symptoms of HD by self-report was studied. The Wechsler Adult Intelligence Test--Revised and a neurological rating scale were administered. The genotypes of 394 individuals were then determined by polymerase chain reaction testing. On all portions of the WAIS-R test, the mean score of the HD gene carriers was lower than that of the noncarriers. Scores on two of the performance subtests, the digit symbol and the picture arrangement, were significantly different in the two groups, even after the scores from all gene carriers who were diagnosed as affected based on their neurological motor examination were removed. The scores for the gene carriers on the various subtests were negatively correlated with the number of CAG repeats in the expanded HD allele. Such a relationship was not seen with the normal alleles of the noncarriers. Taken together, our results suggest that a deficit in cognitive function is an early finding of HD and that in this patient population, the degree of cognitive deficit is proportional to the number of CAG repeats in the HD allele.

Adult↗

PubMed1995

Comparison of analysis of variance and maximum likelihood based path analysis of twin data: partitioning genetic and environmental sources of covariance.

In order to investigate currently used model fitting strategies for twin data, analysis of variance (ANOVA) and path-maximum-likelihood (PATH-ML) methods of analyzing twin data were compared using simulation studies of 50 monozygotic (MZ) and 50 dizygotic (DZ) twin pairs. Phenotypic covariance was partitioned into additive genetic effects (A), environmental effects common to cotwins (C), and environmental variance unique to individuals (E). ANOVA and PATH-ML had identical power to detect total covariance. The PATH-ML AE model was much more powerful than ANOVA comparisons of rMZ and rDZ to detect A. However, to be unbiased, the AE model requires the assumption that C = 0.0. To allow use of the AE model to estimate A, the null hypothesis C = 0.0 is tested by comparing the goodness of fit of the ACE and AE models. Simulation of 50 MZ and 50 DZ pairs revealed that C must be greater than 55% of total variance before the null hypothesis would be rejected (P < 0.05) 80% of the time. Several recent publications were reviewed in which the null hypothesis C = 0.0 was accepted and apparently upwardly biased estimates of A, containing C, were presented with unrealistic P values. It was concluded that use of the AE model to estimate A gives an inflated view of the power of relatively small twin studies. It was recommended that ANOVA or comparison of the ACE and CE PATH-ML models be used to estimate and test the significance of A as neither requires that C = 0.0.

Analysis of Variance↗

PubMed1995

Intrapair differences in personality and cognitive ability among young monozygotic twins distinguished by chorion type.

We evaluated placentation effects on behavioral resemblance of 44 pairs of monozygotic (MZ) twin children. Tested at ages 4-6, the twins' zygosity and placental type had been determined at their delivery. The sample included 23 monochorionic (MC) and 21 dichorionic (DC) MZ twin pairs: DC-MZ twins result from separation of blastomeres within 72 h of ovulation; MC-MZ twins arise from later duplication of the inner cell mass. Twins were individually administered the McCarthy Scales of Cognitive Ability, while their mothers separately rated each cotwin on an individualized 280-item form of the Personality Inventory for Children (PIC). Absolute differences between MC-MZ cotwins were smaller than those between DC-MZ cotwins for all 20 PIC scales, significantly so for 3 of 4 factor scales, 8 of 12 clinical scales, and 2 of 4 validity/screening scales from the PIC; in contrast, no consistent differences in intrapair resemblance of mono- and dichorionic MZ twins were found for the McCarthy Scales. The chorion differences found in the PIC data cannot be due to genetic differences, because all pairs are monozygotes; nor are they associated with differences in parity, gestational age, birth weight, maternal education, palmar dermatoglyphic asymmetry, or maternal knowledge of chorion type. We interpret our findings as suggestive evidence that variation in timing of embryological division, with effects on MZ twins' placental vasculature, has significant consequences for some dimensions of their behavioral development, as well.

Child↗

PubMed1995

Self-reported alcohol intake and cognition in aging twins.

OBJECTIVE: To determine the relationship between long-term alcohol intake and cognitive functioning in aging Caucasian men. METHOD: A retrospective cohort and co-twin-control study of self-reported alcohol intake and cognitive testing using the National Academy of Sciences-National Research Council (NAS-NRC) Twin Panel of U.S. veterans (born between 1917 and 1927). The study included 4,739 twins with two self-reported drinking histories (1970s and 1980s) and a telephone mental status interview (1990 and 1991) that also included 145 individuals with a diagnosis of alcoholism. RESULTS: Age and education adjusted cognitive scores were lower (p < .05) in diagnosed alcoholics than in the remainder of the subjects. To compare age and education adjusted cognitive scores in alcohol intake, the 4,739 twins were divided, based upon questionnaire data, into nondrinkers and 5 quintiles of drinkers by average reported drinks of alcohol weekly (< 1.0, 1-3.3, 3.4-8.1, 8.2-16.0, > 16.0). Past drinkers had scores lower (p < .05) than nondrinkers and all but quintiles 1 and 5 of the drinkers. The light drinkers in quintile 1 and the heavy drinkers in quintile 5 scored lower (p < .05) than the moderate drinkers in quintile 4. Monozygotic twins in quintile 4 scored higher (p < .05) than their co-twins in quintiles 1-3. CONCLUSIONS: No evidence was found to indicate an association between moderate long-term alcohol intake and lower cognitive scores in aging individuals. There was a suggestion of a small protective effect of past moderate alcohol intake on cognitive function with aging.

Aged↗

PubMed1995

World War II-veteran male twins who are discordant for alcohol consumption: 24-year mortality.

The role of genetic and shared environmental influences in the association of alcohol with mortality was studied by using the National Academy of Sciences-National Research Council World War II-veteran male twin registry. An epidemiologic questionnaire administered from 1967 through 1969 permitted identification of twin pairs discordant for alcohol consumption. The subsequent 24 years of mortality follow-up yielded data on time and cause of death. Analyzing the first or only death in drinking-discordant pairs, we observed 27 deaths in abstainer twins and 14 deaths in their light- to moderate-drinker cotwins (relative risk [RR] = 1.93). Excess mortality in twin abstainers was also indicated for deaths from cardiovascular diseases (RR = 2.0) and other causes of death excluding cancers (RR = 3.2). The protective effect, however, of light to moderate drinking did not persist in twins who were smokers at baseline.

Alcohol Drinking↗

PubMed1994

Concordance of smooth pursuit and saccadic measures in normal monozygotic twin pairs.

Although the range of normal ocular motor performance is broad, little is known about the sources of variability. Genetic transmission of eye movement deficits has been described but such possible control of normal function has been little investigated. Characteristics of smooth pursuit and saccades can be examined for the degree of concordance in related individuals. In this pilot study, we studied saccades and pursuit in eight monozygotic (MZ) twin pairs. The statistical analysis of the data used the intraclass correlation of MZ twins (rMZ) to estimate what fraction the covariance of the twin pairs was of the population variance. All saccadic measures showed significant MZ correlations (p < 0.05). Smooth pursuit gains were even more highly correlated (p < 0.001). These results indicate considerable similarity within pairs of twins, particularly for horizontal smooth pursuit, and suggest that larger studies on monozygotic and dizygotic twins would be desirable, to help separate out the relative contributions of environmental and genetic factors.

Adult↗

PubMed1994

Genetic influences on age-related change in total cholesterol, low density lipoprotein-cholesterol, and triglyceride levels: longitudinal apolipoprotein E genotype effects.

This study addressed the possible influence of apolipoprotein E (apo E) genotype on age-related changes in total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), and triglyceride (TG) levels in older males. Apo E is a component of LDL, is a ligand for the LDL receptor, and apo E genotype has been consistently associated with variation in mean levels of TC and LDL-C, and also appears to influence TG levels. Using male twins followed longitudinally between mean ages of 48 and 63 years, the change in TC, LDL-C, and TG over time for individuals with the epsilon 3 epsilon 3 and the epsilon 3 epsilon 4 genotypes was contrasted. At exam 1 mean TC and LDL-C levels were lower in the epsilon 3 epsilon 3 group than in the epsilon 3 epsilon 4 group, but at exam 3 mean TC and LDL-C levels were significantly higher in the epsilon 3 epsilon 3 group than in the epsilon 3 epsilon 4 group. The rate of change in TC and LDL-C with age differed significantly between epsilon 3 epsilon 3 and epsilon 3 epsilon 4 groups. Results for TG were not statistically significantly. These findings suggest that the apo E genotype effects on risk of coronary artery disease may be age-dependent. This study demonstrates the value of longitudinal studies in refining models for genetic risk factors for disease.

Adult↗

PubMed1994

Heritable features of the auditory oddball event-related potential: peaks, latencies, morphology and topography.

Baseline auditory ERP data from a larger study of the genetic determinants of the response to alcohol were collected from 59 monozygotic (MZ) twin pairs and from 39 same-sex dizygotic (DZ) twin pairs who drank socially. Three methods for measuring genetic influence on the ERPs were applied. First, based on maximum-likelihood estimates, the heritability of conventional peak amplitude and latency of N1 and P3 components was computed for each of 16 lead locations using tests of the significance of heritability based on intraclass correlations. P3 amplitude provided the strongest results, distributed symmetrically over caudal leads, and implied gene dominance as the mode of genetic transmission for the P3 component. A substantial genetic influence on N1 latency suggested a mixture of additive and dominance effects in the left fronto-temporal regions. N1 amplitude measures trended towards significant heritability, but none was observed for P3 latency. The second method used the maximum of the cross-correlation function to compare wave form shape in a lead-by-lead analysis of data from cotwins. Genetic influence was apparent in both target and non-target ERP responses, with a fronto-central topography of significant results. The third method reduced all spatial and temporal ERP differences from a pair of twins to a single scalar number for each response. Distributions of this global measure revealed significant genetic influence on both non-target and target ERPs. A post hoc analysis of the effect of gender on the heritability of N1 or P3 peaks and latencies revealed no statistically significant observations in this sample of young adult twins.

Acoustic Stimulation↗

PubMed1994

16-year incidence of ischemic heart disease in the NHLBI twin study. A classification of subjects into high- and low-risk groups.

Prospective data from the National Heart, Lung, and Blood Institute (NHLBI) Twin Study were used to investigate the relationship of risk factors measured in 1970 to 1971 to 16-year incidence of ischemic heart disease (IHD) in 905 males born between 1917 and 1927. A newly developed methodology, tree-structured survival analysis (TSSA), was used to classify subjects into discrete subgroups that differed significantly in profiles of risk factors and incidence of IHD. On the basis of five characteristics--systolic blood pressure (SBP), high-density-lipoprotein cholesterol (HDL-C), 1-hour postload glucose levels, forced expiratory volume in 1 second (FEV1), and a family history score for heart disease--the TSSA algorithm partitioned the cohort into six discrete subgroups that formed three clusters of individuals with distinct IHD experience. Highest IHD incidence rates were experienced by a subgroup of 56 men with baseline SBP above 134 mm Hg and HDL-C levels lower than 33 mg/dL. No IHD events were observed in a subgroup of 117 men who had low SBP, high FEV1, and a negative family history of heart disease. Relationships to the twinning condition showed that for both zygosities, cotwin-pair members were in the same risk subgroup more often than expected; however, the overall difference between the frequency of monozygotic (MZ) and dizygotic (DZ) cotwins was relatively small. The highest MZ/DZ ratios of observed to expected cotwin-pair membership occurred in subgroups with the highest and lowest incidences of IHD, suggesting that these extremes of incidence are most likely to be genetically determined.

Aged↗

PubMed1994

Influences on skeletal mineralization in children and adolescents: evidence for varying effects of sexual maturation and physical activity.

OBJECTIVE: To establish rates of skeletal mineralization in children and adolescents, and to identify factors that influence these rates. DESIGN: Three-year observational study. SETTING: University hospital. SUBJECTS: Ninety white children, aged 6 to 14 years. MEASUREMENTS: Bone mineral density of the radius, spine, and hip was measured at baseline and 3 years later. Physical activity was assessed by questionnaires at 6-month intervals and dietary calcium intake by diet diary 1 day per month for 36 months. Sexual maturation (Tanner stage) was determined by an endocrinologist at 6-month intervals, as necessary to classify children as prepubertal, peripubertal, or postpubertal. RESULTS: Skeletal mineralization accelerated markedly at puberty in the spine (0.077 vs 0.027 gm/cm2 per year, peripubertal vs prepubertal) and greater trochanter (0.050 vs 0.027 gm/cm2 per year), less markedly in the femoral neck (0.047 vs 0.030 gm/cm2 per year), and only slightly in the radius. Nearly one third (15 gm) of the total skeletal mineral in the lumbar spine of adult women (approximately 52 gm) was accumulated in the 3 years around the onset of puberty. Increases in height and weight were the strongest correlates of skeletal mineralization: weight changes were more strongly correlated with trabecular bone sites and changes in height with cortical bone sites. Increases in calf muscle area were strongly associated with mineralization, particularly in peripubertal children, and physical activity was associated with more rapid mineralization in prepubertal children. CONCLUSIONS: Puberty has varying effects on skeletal mineralization depending on skeletal site; trabecular bone is apparently more sensitive to changing hormone concentrations. Physical activity and normal growth are also positively associated with skeletal mineralization, also depending on skeletal site and sexual maturation.

Adolescent↗

PubMed1994

Correlations of alcohol consumption with related covariates and heritability estimates in older adult males over a 14- to 18-year period: the NHLBI Twin Study.

Consistent maximum-likelihood heritability estimates of consumption of alcoholic beverages were observed at three separate times during a 14- to 18-year period in adult twin males initially aged 42-56 years in 1969-1973. Log transformation of the average number of drinks/week of the returnees to all three examinations was examined relative to potential covariates representing both antecedents of drinking alcohol and consequences of alcohol consumption. Significant relationships were noted for 38 of the covariates at one or more of the separate examinations, including positive correlations with smoking, coffee consumption, high-density lipoprotein cholesterol, mean corpuscular volume, systolic blood pressure, uric acid and behavioral measures, and negative correlations with blood urea nitrogen, red blood cell count, tea consumption, and tricep skinfolds. Analysis of the average alcohol consumption adjusted for nine independent covariates selected from multiple stepwise regression resulted in a modest decline in maximum-likelihood heritability estimates compared with unadjusted data, but little difference from heritability estimates obtained when abstainers from alcohol (no alcoholic beverages consumed at all three examinations) were excluded. The most striking effect of omitting abstainers from alcohol was the decline in the intraclass correlations in dizygotic twins. Bivariate analyses of alcohol and individual covariates revealed the phenotypic correlation between alcohol consumption and a measure of hostility was primarily environmental, that for high-density lipoprotein, smoking and coffee drinking with alcohol was primarily genetic, and the phenotypic correlation between alcohol consumption and mean corpuscular volume had both significant genetic and environmental correlations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Hereditary influences on cognitive functioning in older men. A study of 4000 twin pairs.

OBJECTIVE: To determine the contribution of genetic factors to cognitive functioning in older men. DESIGN: Cognitive testing by telephone interview in an epidemiologically defined population. PARTICIPANTS: 2077 monozygotic and 2225 dizygotic male twin pairs, all between the ages of 62 and 73 years, recruited from the National Academy of Sciences twin registry. MAIN OUTCOME MEASURES: The Telephone Interview for Cognitive Status--Modified total score and factor scores were analyzed. The Falconer heritability statistic and maximum likelihood estimates of genetic and environmental components were computed. RESULTS: Heritability of the total Telephone Interview for Cognitive Status--Modified score was estimated to be 30%. Shared environmental effects accounted for an additional 18% of the variance; most of this was related to years of education. Of the four cognitive factors derived, the language/attention factor had the highest heritability estimate. CONCLUSIONS: Genetic factors and educational achievement together account for almost half of the variance in the cognitive functioning of older men. Studies of the genetics of dementing illnesses need to consider the degree to which cognitive capacities are themselves under genetic control.

Aged↗

PubMed1993

The NHLBI male veteran twin study data.

The National Heart, Lung and Blood Institute (NHLBI) twin study is a collaborative, longitudinal study of the role of genetic risk factors on subsequent cardiovascular disease processes in 514 pairs of white, male World War II and Korean veteran twins born between 1917 and 1927. This paper describes the sampling procedures and zygosity determination at the initial examination, participation by the cohort members at later examinations, and a summary of the variables provided for Genetic Analysis Workshop 8 (GAW8).

Aged↗

PubMed1993

The use of monozygotic and dizygotic twins to estimate the effects of inheritance on the levels of immunoglobulin isotypes and antibodies to phosphocholine.

In the elderly there is a pronounced increase in susceptibility to infectious disease. Evidence for particular immune deficits that result in susceptibility to specific agents is lacking, however, and there is little information on the degree to which differences in the susceptibility among the elderly are due to genetic versus environmental effects. A strong association has been observed between eventual fatal pneumonia and elevated levels of IgM antibody to phosphocholine (PC) levels at age 70. In this study we evaluated the heritability of IgM and IgG antibody levels to phosphocholine in the elderly using monozygotic and dizygotic male twins. We observed genetic regulation of serum levels of IgM antibody to PC, a finding which suggests that susceptibility of the elderly to fatal pneumonia may be heritable. Levels of total IgM were under separate genetic control and there was no genetic effect on IgG and IgA levels or levels of IgG antibody to phosphocholine.

Aged↗

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↗

PubMed1992

Long-term bone loss in men: effects of genetic and environmental factors.

OBJECTIVE: To identify environmental factors associated with bone loss in adult male twins and to determine the extent to which shared environmental characteristics affect estimates of the genetic influence on bone loss. DESIGN: A 16-year cohort study. SETTING: A midwestern university hospital. PARTICIPANTS: One hundred and eleven male veterans of World War II or the Korean conflict, born between 1916 and 1927. All were twins, with the sample comprising 48 pairs and 15 persons whose twin brothers were deceased or seriously ill. MEASUREMENTS: Bone mass and environmental characteristics (cigarette smoking, alcohol consumption, physical activity, dietary calcium intake, use of thiazide diuretics) measured at baseline and 16 years later. RESULTS: Rates of radial bone loss averaged 0.45% per year. Those who both smoked and used alcohol at levels greater than the median for the population had a rate of bone loss (10% in 16 years) twice the rate of those who were below the median level for both variables (5% bone loss, P = 0.003). Rates of bone loss were correlated within twin pairs, and these correlations were diminished 25% to 35% by adjustments for environmental influences on bone loss. However, statistically significant within-pair correlations remained (r = 0.4), which did not differ between monozygotic and dizygotic twin pairs after adjustments for smoking, alcohol use, dietary calcium intake, and exercise. CONCLUSIONS: Bone loss in men during mid-life is determined, at least in part, by environmental factors, including smoking, alcohol intake, and, possibly, physical activity. Rates of bone loss were similar within twin pairs, apparently because of a shared environment.

Alcohol Drinking↗

PubMed1992

Calcium supplementation and increases in bone mineral density in children.

BACKGROUND: Increased dietary intake of calcium during childhood, usually as calcium in milk, is associated with increased bone mass in adulthood; the increase in mass is important in modifying the later risk of fracture. Whether the increase is due to the calcium content of milk, however, is not certain. METHODS: We conducted a three-year, double-blind, placebo-controlled trial of the effect of calcium supplementation (1000 mg of calcium citrate malate per day) on bone mineral density in 70 pairs of identical twins (mean [+/- SD] age, 10 +/- 2 years; range, 6 to 14). In each pair, one twin served as a control for the other; 45 pairs completed the study. Bone mineral density was measured by photon absorptiometry at two sites in the radius (at base line, six months, and one, two, and three years) and at three sites in the hip and in the spine (at base line and three years). RESULTS: The mean daily calcium intake of the twins given placebo was 908 mg, and that of the twins given calcium supplements was 1612 mg (894 mg from the diet and 718 mg from the supplement). Among the 22 twin pairs who were prepubertal throughout the study, the twins given supplements had significantly greater increases in bone mineral density at both radial sites (mean difference in the increase in bone mineral density: midshaft radius, 5.1 percent [95 percent confidence interval, 1.5 to 8.7 percent]; distal radius, 3.8 percent [95 percent confidence interval, 1.4 to 6.2 percent]) and in the lumbar spine (increase, 2.8 percent [95 percent confidence interval, 1.1 to 4.5 percent]) after three years; the differences in the increases at two of three femoral sites approached significance (Ward's triangle in the femoral neck, 2.9 percent; greater trochanter, 3.5 percent). Among the 23 pairs who went through puberty or were postpubertal, the twins given supplements received no benefit. CONCLUSIONS: In prepubertal children whose average dietary intake of calcium approximated the recommended dietary allowance, calcium supplementation increased the rate of increase in bone mineral density. If the gain persists, peak bone density should be increased and the risk of fracture reduced.

Absorptiometry, Photon↗