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Biomedical subjects

Chandra A Reynolds

Publications and source records attributed to Chandra A Reynolds.

At least 19 recordsLinked to original sources

Prediction of alcohol consumption: The role of genetics, impulsivity, and sensation seeking from adolescence to adulthood.

BACKGROUND: There are well-known phenotypic and genetic associations among impulsivity, sensation seeking (SS), and alcohol consumption, but whether they vary between adolescence and early adulthood remains unclear. PURPOSE/HYPOTHESES: We hypothesized that adolescent alcohol consumption would be better predicted by polygenic indices (PGIs) of impulsivity and SS than PGIs of adult alcohol consumption (drinks per week; DPW), but that the reverse would be observed in young adulthood (i.e., stronger associations for DPW PGIs). METHODS: N = 733-754 twins of European genetic ancestry from the Colorado Longitudinal Twin Study were assessed at age 17 and/or 23 years using structural equation modeling. RESULTS: The SS PGIs were associated with alcohol consumption in adolescence (β=0.16), whereas DPW PGIs were associated with alcohol consumption in early adulthood (β=0.15). Additionally, phenotypic measures of impulsivity and SS are associated with alcohol consumption at both ages (β=.13-.21) and mediated some PGI-alcohol associations. DISCUSSION: These findings suggest that genetic influences on alcohol consumption change from adolescence to early adulthood, with genetic influences on sensation seeking most relevant to alcohol consumption in adolescence.

Humans↗

Evaluating a Genome-Wide Polygenic Score for Handgrip Strength and Its Interplay with Leisure-Time Physical Activity Across the IGEMS Twin Cohorts.

PURPOSE: Polygenic scores (PGSs) may help assess genetic predisposition to multifactorial traits. We examined whether age, sex, and leisure-time physical activity (LTPA) modify the association between a PGS for handgrip strength (HGS) and measured HGS in older adults. METHODS: PGS for HGS (PGS hgs) , based on Pan-UK Biobank genome-wide association study data, was calculated for 5103 participants (aged 40-96; 44% women) from eight twin cohorts in Denmark, Sweden, Australia, the United States, and Finland within the IGEMS consortium. Sex-standardized HGS and self-reported LTPA were assessed cross-sectionally. Linear mixed models estimated associations between PGS hgs and HGS, including interactions with age, country, and LTPA, as well as an association between PGS hgs and LTPA. Fixed-effect within-pair models were conducted to assess environmental contributions. RESULTS: Higher PGS hgs was associated with greater HGS (&#x3b2; = 2.14, SE = 0.15, P < 0.001), explaining 4.6% of HGS variance overall, with modest variation across countries. In sex-stratified models, PGS hgs explained 5.2% of the variance in females and 4.3% in males. No statistically significant interaction with age was found. A significant PGS hgs &#xd7; LTPA interaction (&#x3b2; = -0.034, P = 0.013) indicated that the association between LTPA and HGS was more pronounced among individuals with lower PGS hgs . The within-pair models offered limited support for the independent environmental impact of LTPA. CONCLUSIONS: The PGS hgs was associated with measured HGS in the meta-analysis, highlighting the potential of PGSs to capture individual differences in strength-related traits across populations. The association of PGS hgs with HGS was moderated by LTPA, such that the beneficial impact of LTPA on HGS was greater among individuals with a lower genetic propensity for HGS.

Humans↗

Differential methylation clock ages across buffy coat (BC), peripheral blood mononuclear cells (PBMC), and saliva in individuals approaching midlife.

Understanding epigenetic aging prior to midlife is gaining interest as a potentially intervenable period to address factors that influence health and cognitive aging. Epigenetic changes associated with aging may point to differential biological aging rates; however, methylation profiles may not be substitutable across tissues. We compared DNA methylation in three tissues collected in 91 siblings and twins from the Colorado Adoption/Twin Study of Lifespan behavioral development and cognitive aging (CATSLife1): saliva, buffy coat (BC), and peripheral blood mononuclear cells (PBMC). Overall, across five methylation clocks and two blood-derived and one saliva-derived tissues, moderate to strong associations between chronological age and methylation ages were observed. Moreover, PBMC methylation age values correlate more strongly with BC values (Spearman r = 0.66 - 0.87), whereas saliva showed weaker correlations with either form of blood-derived measures (Spearman r = 0.25 - 0.69) although still moderate to strong magnitudes. Saliva demonstrated significantly older methylation ages across four of five clocks, whereas PBMC and BC did not differ. Twins were more strongly correlated for BC and PBMC derived clocks with weaker and inconsistent patterns among Saliva clocks. DunedinPACE age acceleration showed no significant tissue differences and on average demonstrated the largest divergence of similarity between monozygotic (MZ) versus dizygotic (DZ) twins (rMZ= .56, rDZ= .21). In summary, saliva-derived methylation is not a direct substitute for blood-derived methylation whereas blood-derived methylation values were comparable across buffy coat and peripheral blood mononuclear cell tissues.

age acceleration↗

Alcohol, tobacco and caffeine use: spouse similarity processes.

Spouse similarity research has been largely descriptive yet is of theoretical and empirical importance to understanding individual differences in substance use. The present study considers phenotypic assortment versus social homogamy processes for alcohol, tobacco, and caffeine consumption traits using an extended twin-spouse design. Whereas both assortment processes were supported for quantity of alcohol consumed, phenotypic assortment was supported for quantity of tobacco and caffeine consumed, and social homogamy for tobacco use status. Moderate heritable influences were found for all traits though no shared environmental influences were found beyond those due to social background influences, i.e. those pertaining to social homogamy. Swedish government policies in effect at the time of marriage selection may explain the presence of social homogamy for quantity of alcohol versus quantity of tobacco and caffeine consumed. Social homogamy may be more important for some substance use traits such as alcohol consumption and tobacco use status but not others.

Adult↗

Longitudinal memory performance during normal aging: twin association models of APOE and other Alzheimer candidate genes.

The APOE gene (apolipoprotein E) is a major risk factor for Alzheimer's Disease (AD) but has been inconsistently associated with memory in nondemented adults. Two other genes with mixed support as genetic risk factors for AD, A2M (alpha-2-macroglobulin) and LRP (low-density lipoprotein receptor-related protein), have not been studied in relation to memory among nondemented adults. The present study examined these three genes and latent growth parameters estimated from memory performance spanning 13 years in 478 twins from the Swedish Adoption/Twin Study of Aging (SATSA). APOE was associated with working and recall memory ability levels and working memory rate of change, with e4 homozygotes exhibiting the worst performance at all ages. Homozygotes for the rare A2M insertion/deletion variant exhibited accelerating decline on delayed figural recognition. There were no significant findings for LRP. Dominance, often untested in previous studies, was important in the current study's findings.

Age Factors↗

Role of genes and environments for explaining Alzheimer disease.

CONTEXT: Twin studies using selected samples have shown high heritability for Alzheimer disease (AD). OBJECTIVE: To evaluate genetic and environmental influences on AD in a fully ascertained population of older twins, including like- and unlike-sex pairs. DESIGN: Five-group quantitative genetic model: male monozygotic twins, female monozygotic twins, male dizygotic twins, female dizygotic twins, and unlike-sex twins. SETTING AND PARTICIPANTS: All twins in the Swedish Twin Registry aged 65 years and older. The study included 11,884 twin pairs, among whom were 392 pairs in which 1 or both members had AD. MAIN OUTCOME MEASURES: All individuals were screened for cognitive dysfunction. Suspected cases of dementia and their co-twins received complete clinical diagnostic evaluations for AD. Estimates of heritability, shared environmental influences, and nonshared environmental influences, adjusting for age, were derived from the twin data. RESULTS: Heritability for AD was estimated to be 58% in the full model and 79% in the best-fitting model, with the balance of variation explained by nonshared environmental influences. There were no significant differences between men and women in prevalence or heritability after controlling for age. Within pairs concordant for AD, intrapair difference in age at onset was significantly greater in dizygotic than in monozygotic pairs, suggesting genetic influences on timing of the disease. CONCLUSIONS: In the largest twin study to date, we confirmed that heritability for AD is high and that the same genetic factors are influential for both men and women. However, nongenetic risk factors also play an important role and might be the focus for interventions to reduce disease risk or delay disease onset.

Age of Onset↗

Longitudinal change in memory performance associated with HTR2A polymorphism.

We present a fresh approach to evaluating association with candidate genes and cognitive change by testing association for parameters describing individual growth curves from twins. Moderate genetic influences on memory in aging adults has been shown in quantitative genetic studies. A recently reported, association of a HTR2A polymorphism with episodic memory in young unrelated adults led us to investigate the association between a nearby polymorphism and longitudinal memory performance in the Swedish Adoption/Twin Study of Aging (SATSA). Analysis of growth curve parameters suggests that both how well individuals perform on figural memory at age 65 years and nonlinear change in figural memory performance across age are associated with HTR2A. Individuals with two copies of the common G allele demonstrated higher figural memory performance longitudinally than those with the less frequent A allele, with performance trajectories differing by 2-6% per year. These findings imply a role for the 5-HT2A serotonin receptor on the formation of episodic memories in older adults.

Age Distribution↗

Heritability of an age-dependent categorical phenotype: cognitive dysfunction.

We investigated the extent to which cognitive dysfunction is shaped by genetic or environmental influences, and whether these factors differ in women and men. All members of the Swedish Twin Registry aged 65 and older were screened by telephone using the TELE, a brief cognitive assessment instrument (Gatz et al., 2002), and the Blessed Dementia Rating Scale (Blessed et al., 1968) from relatives of those who scored poorly on the TELE. Data were available for 4308 pairs where both members responded and 5070 pairs where only one member was alive and participated. To analyze all available data, we used a raw data method extended to ordinal data. As the prevalence of cognitive dysfunction increases with age, we incorporated age-adjusted thresholds. The best fitting model from biometric analyses indicated 35% of the variation in liability to cognitive dysfunction could be explained by heritable influences and the remaining 65% by nonfamilial environmental influences. Differences by gender were not significant. As this is a normative population including cognitively intact individuals, preclinical dementia cases and demented individuals, the relative magnitude of genetic and environmental effects is of particular interest in light of high heritabilities found for dementias such as Alzheimer's disease. The findings emphasize the extent to which research is needed to uncover nonfamilial environmental influences on cognitive dysfunction in later life.

Age of Onset↗

Surprising lack of sex differences in normal cognitive aging in twins.

Sex differences in the etiology of normal cognitive functioning in aging remain largely unexplored. We conducted an investigation of genetic and environmental contributions to sex differences in level of cognitive performance and rate of decline in the Swedish Adoption/Twin Study of Aging (SATSA) (Finkel & Pedersen, 2004) data set. Behavioral genetic parameterizations of a latent growth curve model were fit to longitudinal data on 11 cognitive measures. Seven hundred and ninety-eight non-demented individuals had cognitive data across four waves of measurement covering 13 years. Participants ranged in age from 44 to 88 at first testing wave; 60% were female. Results indicated sex differences in mean performance for five cognitive measures and in rates of decline for Information and Card Rotations. Only Synonyms demonstrated sex differences in genetic and environmental contributions to mean performance: heritability was higher in men than women. Despite differential longevity and susceptibility to disease, there are no consistent indications that men and women show different patterns of cognitive aging.

Adult↗

The longitudinal relationship between processing speed and cognitive ability: genetic and environmental influences.

Goals of the present study were to investigate the relationship between age changes in speed and cognition and the genetic and environmental influences on that relationship. Latent growth models and quantitative genetic methods were applied to data from the Swedish Adoption/Twin Study of Aging. The sample included 778 individuals from both complete and incomplete twin pairs who participated in at least 1 of 4 testing occasions over a 13-year-period. Four factors were constructed from 11 cognitive measures: verbal, spatial, memory, and processing speed. Results indicate that for measures of fluid abilities, the explanatory value of processing speed is paramount for both mean cognitive performance and acceleration with age. A significant proportion of the genetic influences on cognitive ability arose from genetic factors affecting processing speed. For measures of fluid abilities, it is not the linear age changes but the accelerating age changes in cognition that share genetic variance with processing speed.

Aged↗

Complete ascertainment of dementia in the Swedish Twin Registry: the HARMONY study.

The purpose of this report is to describe the Study of Dementia in Swedish Twins (known as HARMONY), including procedures for complete ascertainment of all cases of Alzheimer's disease (AD) and other dementias in 14,435 individuals aged 65 and older from the national Swedish twin registry. Telephone cognitive screening identified 11.5% as positive for cognitive dysfunction. Clinical diagnoses were completed for 1557 individuals, including individuals who screened positive, their twin partners, and a sample of normal controls. Estimated prevalence of dementia ranged from 1.4% for age 65-69 to 29.2% for age 90 and older. Concordance rates for Alzheimer's disease were 59% for monozygotic twins, 32% for like-sexed, and 24% for unlike-sexed dizygotic twins. Among monozygotic twins where both twins had Alzheimer's disease, the within pair difference in age of onset ranged from both becoming demented in the same year to 7 years difference in onset.

Age Factors↗

Quantitative genetic analysis of latent growth curve models of cognitive abilities in adulthood.

Though many cognitive abilities exhibit marked decline over the adult years, individual differences in rates of change have been observed. In the current study, biometrical latent growth models were used to examine sources of variability for ability level (intercept) and change (linear and quadratic effects) for verbal, fluid, memory, and perceptual speed abilities in the Swedish Adoption/Twin Study of Aging. Genetic influences were more important for ability level at age 65 and quadratic change than for linear slope at age 65. Expected variance components indicated decreasing genetic and increasing nonshared environmental variation over age. Exceptions included one verbal and two memory measures that showed increasing genetic and nonshared environmental variance. The present findings provide support for theories of the increasing influence of the environment with age on cognitive abilities.

Adoption↗

Performance on neurocognitive tests by co-twins to dementia cases compared to normal control twins.

Nondemented co-twins of twins who were diagnosed as demented were compared to randomly selected members of normal control twin pairs in which both members of the pair were nondemented. Nondemented co-twins included 23 monozygotic and 62 dizygotic twins; there were 27 normal control twins. Both monozygotic and dizygotic nondemented co-twins of dementia cases scored significantly lower than normal control twins on 5 of 10 cognitive tests. Moreover, monozygotic co-twins of dementia cases had a generally lower score profile than dizygotic co-twins of dementia cases did. These findings show that being at greater genetic risk for dementia is reflected in cognitive performance even in the absence of a diagnosis of dementia.

Aged↗

Comparative rating measures of health and environmental exposures: how well do twins agree?

Twins are sometimes used as proxy informants but little is known about reliability and validity of the information thus obtained. The present study asks: (1) to what extent do twin pairs agree with each other on comparative ratings of health, psychosocial traits, and environmental exposures?; and (2) how well do comparative ratings agree with usual self-reported information about the exposures? Using 55 monozygotic (MZ) and 71 dizygotic (DZ) same-sex pairs reared together, percentage agreement was calculated for 44 comparative ratings. Pairs agreed on average about half of the time. Agreement was higher for more discrete exposures, such as smoking, but lower for more subjective variables, such as the degree to which life is experienced as stressful. Signed rank tests were used to contrast comparative ratings to differences in self-reports. Differences between twin partners in their self-report indices, where available, were in the direction suggested by the comparative rating. Comparative ratings appear most accurate for smoking and alcohol use, and less consistent for mental health symptoms and self-rated health.

Adult↗

Genetic and environmental influences on decline in biobehavioral markers of aging.

Latent growth models were applied to longitudinal twin data on markers of aging to investigate genetic and environmental influences on the processes of change with age. The sample included 1957 participants aged 50 to 96 years. Five markers were assessed: forced expiratory volume, mean arterial pressure, grip strength, motor functioning, and well-being. Data were gathered at up to three follow-up occasions at intervals of 3 years. Results indicated monotonic changes with age for all but two variables. Performance on motor functioning and well-being was stable until age 65 or 70, followed by significant decline. Genetic influences on the level of performance were indicated for all five markers of aging. Genetic influences on the slope were found for only three of the variables: motor functioning, mean arterial pressure, and forced expiratory volume. Investigations of the aging process will differ depending on whether the focus is on static performance or change.

Aged↗

Sex differences in genetic risk for dementia.

We used two Swedish twin samples to test whether women are at greater risk than men of developing dementia and whether there are sex differences in mechanisms underlying dementia and cognitive dysfunction. Dementia analyses found no sex differences in incidence of dementia or Alzheimer's disease among initially intact participants followed longitudinally. Twin analyses indicated a substantial genetic influence on liability to incident dementia. Although sex differences in model parameters were not statistically significant, for women but not men an equally attractive model included genetic influence due to both additive effects and dominance or epistasis. In the cognitive dysfunction analyses, results from a sex limitation model raise the possibility that either different genes or different environments have a role for men and women. We conclude that women are not at higher risk of developing dementia, but there is a hint that different genetic processes may be involved for women than for men.

Alzheimer Disease↗

Latent growth curve analyses of accelerating decline in cognitive abilities in late adulthood.

Latent growth models were applied to data from the Swedish Adoption/Twin Study of Aging to discover if the rate of change in cognitive performance increased from middle age to later adulthood. The sample included 590 participants aged 44 to 88 years at first measurement. Data were gathered at 2 follow-up occasions at intervals of 3 years. Cognitive ability was assessed through 11 tests that tapped crystallized, fluid, memory, and spatial abilities and perceptual speed. Results indicated stability for measures of crystallized ability, linear age changes for many cognitive abilities, and a significant acceleration in linear decline after age 65 for measures with a large speed component. Gender differences were found only in mean level, not in rate of decline.

Adoption↗