Biomedical subjects

Simon Easteal

Publications and source records attributed to Simon Easteal.

12 recordsLinked to original sources

PubMed2007

APOE genotype and cognitive functioning in a large age-stratified population sample.

There is evidence that the cognitive effects of Alzheimer's disease can be seen decades before disease diagnosis. If this is the case, then the apolipoprotein E (APOE) *E4 allele might be expected to have effects on cognitive functioning earlier in the life span. To assess such effects, the authors examined data on the *E4 allele and cognitive functioning from a population sample of 6,560 Caucasians covering the age groups of 20-24, 40-44, and 60-64 years. Participants were assessed on tests of episodic memory, working memory, mental speed, reaction time, and reading vocabulary. Although performance on all tests except reading vocabulary declined across age groups, there was no effect of the APOE *E4 allele at any age. These results indicate that APOE *E4 does not have preclinical effects early in the life span on these cognitive functions. Cognitive aging effects between the ages of 20 and 64 years must not be due to preclinical Alzheimer's disease.

Adult↗

PubMed2006

SeqVis: visualization of compositional heterogeneity in large alignments of nucleotides.

UNLABELLED: Most phylogenetic methods assume that the sequences evolved under homogeneous, stationary and reversible conditions. Compositional heterogeneity in data intended for studies of phylogeny suggests that the data did not evolve under these conditions. SeqVis, a Java application for analysis of nucleotide content, reads sequence alignments in several formats and plots the nucleotide content in a tetrahedron. Once plotted, outliers can be identified, thus allowing for decisions on the applicability of the data for phylogenetic analysis. AVAILABILITY: http://www.bio.usyd.edu.au/jermiin/programs.htm.

Algorithms↗

PubMed2006

Serotonin transporter polymorphisms and clinical response to sertraline across ethnicities.

The aim of this pilot study was to examine the relationship between clinical response, adverse effects, sertraline (SERT) plasma concentrations and the genetic polymorphism of the serotonin transporter gene-linked polymorphic region (5HTTLPR) in 2 ethnic patient groups. The study involved 45 patients in a clinical trial who received a fixed dose regimen of 50 mg SERT for one week, then a variable-dose regimen for a further 6 weeks for major depressive disorder. At weeks 1 and 6, the following assessments were completed: Hamilton Depression Rating Scale (HDRS), Clinical Global Impression (CGI), drug adverse reaction scale and measurement of plasma SERT levels. Genomic analysis for the long and short allele variants of the 5HTTLPR polymorphism was also carried out. Caucasian subjects had a higher rate of l/l genotype while Chinese subjects had higher frequencies of l/s and s/s genotypes. Comparison of the subjects with the 5HTTLPR s/s genotype and those with the l/l and l/s genotypes found no significant differences in the HDRS scores, CGI scores, response rates, adverse effects and SERT plasma concentrations at week 6.

Adult↗

PubMed2006

Characterization of simple sequence repeat variants linked to candidate genes for behavioral phenotypes.

Simple sequence repeats (SSRs) have traditionally been used as markers in gene mapping studies and typing for forensic purposes. Recently there has been some speculation that this type of genetic variation also plays a more direct role in influencing gene expression and hence complex phenotypic outcomes such as human behavior. For this reason it is interesting to investigate SSRs linked to candidate genes for various complex phenotypes. An economical multiplex PCR-based assay was designed to simultaneously genotype individuals at 15 loci across 10 candidate genes for human behavioural phenotypes, including seven loci previously unreported in Caucasians (five unreported in any population). All loci were tested for Hardy-Weinberg equilibrium and for two-locus Linkage Disequilibrium. Ewens-Watterson neutrality testing indicated possible selection at a previously unreported DRD2 locus.

Adult↗

PubMed2004

Association of adverse childhood experiences, age of menarche, and adult reproductive behavior: does the androgen receptor gene play a role?

Previous research has reported associations between adverse childhood experiences, early menarche, and early sexual activity. One hypothesis to account for these findings is that an X-linked androgen receptor GGC-repeat polymorphism predisposes fathers to behaviors which include family abandonment and their daughters to earlier menarche and sexual activity and less stable relationships. Retrospective data relevant to this theory were examined from a community survey involving 3,702 women in the age groups 20-24, 40-44, and 60-64 years, and another involving 908 women aged 18-79 years. Earlier age of menarche was found to be associated with adverse childhood experiences and earlier sexual activity. However, the androgen receptor gene polymorphism was unrelated to adverse fathering behavior or to marital breakdown.

Adult↗

PubMed2004

The emerging role of pharmacogenetics: implications for clinical psychiatry.

OBJECTIVE: This article aims to review the implications of pharmacogenetics for clinical psychiatry; these are discussed in the context of environmental and sociocultural factors. METHOD: A selective literature review was conducted using Medline search and other relevant references available to the authors. RESULTS: The individual differences in therapeutic and adverse effects of psychotropic drugs are largely determined by genetic factors. Recent advances in pharmacogenetics have highlighted the potential utility in predicting metabolic phenotypes, risks for side-effects and likelihood of drug response for the individual patient. CONCLUSIONS: Genotyping, especially for drug metabolizing enzymes, could enable more rational, cost-effective and optimal prescribing in future psychopharmacotherapy. Although the advances of pharmacogenetics may have many benefits in clinical practice, the importance of non-genetic factors must also be considered as cultural and environmental factors significantly impinge on response to medications. To clarify the extent pharmacogenetics can be adopted in clinical practice to predict drug response in patients from diverse backgrounds, further studies in different ethnic groups and clinical settings are required.

Cost-Benefit Analysis↗

PubMed2003

ACTN3 genotype is associated with human elite athletic performance.

There is increasing evidence for strong genetic influences on athletic performance and for an evolutionary "trade-off" between performance traits for speed and endurance activities. We have recently demonstrated that the skeletal-muscle actin-binding protein alpha-actinin-3 is absent in 18% of healthy white individuals because of homozygosity for a common stop-codon polymorphism in the ACTN3 gene, R577X. alpha-Actinin-3 is specifically expressed in fast-twitch myofibers responsible for generating force at high velocity. The absence of a disease phenotype secondary to alpha-actinin-3 deficiency is likely due to compensation by the homologous protein, alpha-actinin-2. However, the high degree of evolutionary conservation of ACTN3 suggests function(s) independent of ACTN2. Here, we demonstrate highly significant associations between ACTN3 genotype and athletic performance. Both male and female elite sprint athletes have significantly higher frequencies of the 577R allele than do controls. This suggests that the presence of alpha-actinin-3 has a beneficial effect on the function of skeletal muscle in generating forceful contractions at high velocity, and provides an evolutionary advantage because of increased sprint performance. There is also a genotype effect in female sprint and endurance athletes, with higher than expected numbers of 577RX heterozygotes among sprint athletes and lower than expected numbers among endurance athletes. The lack of a similar effect in males suggests that the ACTN3 genotype affects athletic performance differently in males and females. The differential effects in sprint and endurance athletes suggests that the R577X polymorphism may have been maintained in the human population by balancing natural selection.

Actinin↗

PubMed2003

Number of SNPS loci needed to detect population structure.

The study of the association of polymorphic genetic markers with common diseases is one of the most powerful tools in modern genetics. Interest in single nucleotide polymorphisms (SNPs) has steadily grown over the last decade. SNPs are currently the most developed markers in the human genome because they have a number of advantages over other marker types. One of the critical problems responsible for 'spurious' association findings in case-control studies is population stratification. There are many statistical approaches developed for detecting population heterogeneity. However the power to detect population structure by known methods is highly dependent on the number of loci utilised. We performed an analysis of SNPs data available in the public domain from The Single Nucleotide Consortia Ltd. (TSCL). Three populations, Afro-American, Asian and Caucasian, were compared. Estimation of the minimum number of SNPs loci necessary for detection of the population structure was performed. Two clustering approaches, distance-based and model-based, were compared. The model-based approach was superior when compared with the distance-based method. We found more than 65 random SNPs loci are required for identifying distinct geographically separated populations. Increasing the number of markers to over 100 raises the probability of correct assignment of a particular individual to an origin group to over 90%, even with conventional clustering methods.

Genetic Markers↗

PubMed2002

Lack of association of a single-nucleotide polymorphism of the mu-opioid receptor gene with anxiety-related traits: results from a cross-sectional study of adults and a longitudinal study of children.

There is evidence from animal experiments that the mu- and delta-opioid receptors may play a role in anxiety and depression. It might therefore be expected that functional polymorphisms of these genes in humans are associated with anxiety and depression. We investigated a single-nucleotide polymorphism (Asn40Asp) of the mu-opioid receptor gene (OPRM1). This association was investigated in two samples: 1) a cross-sectional survey of 867 community-living adults aged 18-79 years who were assessed for anxiety and depression symptoms and related personality traits; and 2) a longitudinal study of childhood temperament in which 660 children were followed from infancy to the mid-teens and assessed for anxiety-related temperament and behavior problems. The data did not support a role for the Asn40Asp polymorphism in anxiety and depression, despite adequate statistical power to detect small effects.

Adolescent↗

PubMed2002

Association of polymorphisms of the estrogen receptor gene with anxiety-related traits in children and adolescents: a longitudinal study.

Anxiety problems and associated temperamental traits are multifactorial, determined by the interaction of genetic and environmental factors. Genetic effects may involve both neurotransmitters and hormones. A good candidate gene for association with anxiety-related traits is the estrogen receptor (ESRalpha). Estrogen exerts an effect on mood and behavior in humans through gene regulation on binding to estrogen receptor protein. Association between ESRalpha polymorphism and anxiety-related traits was investigated in a cohort of 680 Australian adolescents studied from 4-8 months to 15-16 years of age. Genotype frequencies were estimated for polymorphic PvuII and XbaI restriction sites in intron 1 and a microsatellite [(TA)(n)] locus 5' of ESRalpha. There was strong linkage disequilibrium between the three loci and a significant sex difference was observed in allele (for (TA)(n), PvuII) and genotype (for XbaI) frequencies. There were no significant allelic or genotypic differences in anxiety-related traits for the three loci tested. However, some significant associations were found for PvuII/(TA)(n) and XbaI/(TA)(n) two-locus genotypes and anxiety, accounting for between 1.6% and 2.8% of the total variance for anxiety in this population. The discordance in Hardy-Weinberg proportions at the XbaI locus between the sexes is an important finding, perhaps indicating a sex-specific role for ESRalpha in fetal survival.

Adolescent↗

PubMed2002

Change in cognitive functioning associated with apoE genotype in a community sample of older adults.

The influence of a genetic risk factor, apolipoprotein E (apoE) epsilon4 variant, was assessed in older adults aged 70 to 94 on 3 occasions over 7 years. The results of latent growth curve analyses are reported for individuals genotyped for apoE at the 2nd measurement occasion (n = 601) and for a subsample of individuals without probable or definite dementia during the 1st or 2nd occasion (n = 434). ApoE-epsilon4 status was a significant predictor of level and change in memory performance and change in speed performance in the full sample, and of initial level and change in memory performance in the nondemented subsample. These results support previous findings that apoE-epsilon4 is associated with accelerated memory deterioration in individuals without clinical dementia.

Aged↗

PubMedDate not supplied

Apolipoprotein E genotype and temperament: a longitudinal study from infancy to the late teens.

OBJECTIVE: To replicate an earlier Finnish study by Keltikangas-Järvinen et al. (5) reporting that the APOE genotype is associated with temperamental traits involving increased activity. METHODS: DNA was collected from 683 Australian children who had participated in a longitudinal study of childhood temperament from 4 to 8 months up to 17 to 18 years. Associations were examined between APOE genotype and a range of measures of activity and hyperactivity. RESULTS: No associations were found. CONCLUSIONS: The earlier Finnish finding could not be replicated despite adequate statistical power.

Adolescent↗