Biomedical subjects

Chandra Reynolds

Publications and source records attributed to Chandra Reynolds.

4 recordsLinked to original sources

PubMed2005

Towards compendia of negative genetic association studies: an example for Alzheimer disease.

Most genetic sequence variants that contribute to variability in complex human traits will have small effects that are not readily detectable with population samples typically used in genetic association studies. A potentially valuable tool in the gene discovery process is meta-analysis of the accumulated published data, but in order to be valid these require a sample of studies representative of the true genetic effect and thus hypothetically should include some positive and an abundance of negative reports. A survey of the literature on association studies for Alzheimer disease (AD) from January 2004-April 2005, identified 138 studies, 86 of which reported positive findings other than for apolipoprotein E (APOE), strongly indicative of publication bias. We report here an analysis of 62 genetic markers, tested for association with AD risk as well as for possible effects upon quantitative indices of AD severity (mini-mental state examination scores, age-at-onset, and cerebrospinal fluid (CSF) beta-amyloid (Abeta) and CSF tau proteins). Within this set, only modest signals were present that, with the exception of APOE are easily lost when corrections for multiple hypotheses are applied. In isolation, results are thus broadly negative. Genes studied encompass both novel candidates as well as several recently claimed to be associated with AD (e.g. urokinase plasminogen activator (PLAU) and acetyl-coenzyme A acetyltransferase 1 (ACAT1)). By reporting these data we hope to encourage the publication of gene compendia to guide further studies and aid future meta-analyses aimed at resolving the involvement of genes in complex human traits.

Aged↗

PubMed2003

The influence of mortality on twin models of change: addressing missingness through multiple imputation.

Twin analyses of phenotypes that are associated with mortality may provide biased heritability estimates if the models require that data from both members of a pair are available. This is particularly true when longitudinal analyses are applied to measures of cognition or biomarkers of aging. The effect of applying imputational techniques that include information on age at death was tested on longitudinal data from two twin studies of aging, each with up to four occasions of measurement. Measures of twin similarity for intercepts and slopes from three latent growth curve models were compared: without imputed data, including imputed data but without information on age at death, and including imputed data with information on age at death. Results indicated that twin similarity for slopes decreases when mortality is accounted for, but that considerable age-related covariation remains.

Humans↗

PubMed2002

Spatial but not verbal cognitive deficits at age 3 years in persistently antisocial individuals.

Previous studies have repeatedly shown verbal intelligence deficits in adolescent antisocial individuals, but it is not known whether these deficits are in place prior to kindergarten or, alternatively, whether they are acquired throughout childhood. This study assesses whether cognitive deficits occur as early as age 3 years and whether they are specific to persistently antisocial individuals. Verbal and spatial abilities were assessed at ages 3 and 11 years in 330 male and female children, while antisocial behavior was assessed at ages 8 and 17 years. Persistently antisocial individuals (N = 47) had spatial deficits in the absence of verbal deficits at age 3 years compared to comparisons (N = 133), and also spatial and verbal deficits at age 11 years. Age 3 spatial deficits were independent of social adversity, early hyperactivity, poor test motivation, poor test comprehension, and social discomfort during testing, and they were found in females as well as males. Findings suggest that early spatial deficits contribute to persistent antisocial behavior whereas verbal deficits are developmentally acquired. An early-starter model is proposed whereby early spatial impairments interfere with early bonding and attachment, reflect disrupted right hemisphere affect regulation and expression, and predispose to later persistent antisocial behavior.

Adolescent↗

PubMed2002

Stimulation seeking and intelligence: a prospective longitudinal study.

The prediction that high stimulation seeking 3-year-olds would have higher IQs by 11 years old was tested in 1,795 children on whom behavioral measures of stimulation seeking were taken at 3 years, together with cognitive ability at 11 years. High 3-year-old stimulation seekers scored 12 points higher on total IQ at age 11 compared with low stimulation seekers and also had superior scholastic and reading ability. Results replicated across independent samples and were found for all gender and ethnic groups. Effect sizes for the relationship between age 3 stimulation seeking and age 11 IQ ranged from 0.52 to 0.87. Findings appear to be the first to show a prospective link between stimulation seeking and intelligence. It is hypothesized that young stimulation seekers create for themselves an enriched environment that stimulates cognitive development.

Achievement↗