Biomedical subjects

Karen A Mather

Publications and source records attributed to Karen A Mather.

3 recordsLinked to original sources

PubMed2026

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 (β = 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 × LTPA interaction (β = -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↗

PubMed2021

1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans.

Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.

Brain↗

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↗