Effects of gene dosage on cognitive ability: A function-based association study across brain and non-brain processes
The researchers assessed the relationship between copy-number variants (CNVs) and cognitive ability using data from six cohorts, including the CARTaGENE cohort. They performed a genome-wide association study (GWAS) with 258,292 individuals, identifying a duplication at 2q12.3 associated with higher cognitive performance. A functional-burden analysis was developed to examine the association between cognition and CNVs disrupting 6,502 gene sets defined across various biological tissues, cell types, and ontologies. Among these, 864 gene sets were linked to cognition, with the effect sizes of deletions and duplications negatively correlated. Deletions affected subcortical regions and postsynaptic functions, while duplications impacted the cerebral cortex and presynaptic functions.
Lower estimated glomerular filtration rate relates to cognitive impairment and brain alterations
The researchers investigated the association between estimated glomerular filtration rate (eGFR) and cognitive function in 15,897 CARTaGENE participants. They found that lower eGFR was linked to reduced cognitive performance and that brain regions associated with eGFR were enriched in mitochondrial and inflammation-related genes. These associations were independent of age, sex, education, BMI, Framingham risk score, and white matter lesion volume.
Exposure to air pollutants and subclinical carotid atherosclerosis measured by magnetic resonance imaging: A cross-sectional analysis
The researchers examined how long-term exposure to air pollution affects early signs of heart disease. They used data to explore whether low levels of air pollutants are linked to the thickening of artery walls. The study included 6,645 adults from five Canadian provinces and estimated their exposure to nitrogen dioxide (NO₂), ozone (O₃), and fine particulate matter (PM2.5) over several years. Using MRI scans to measure carotid artery wall thickness, the researchers found mixed results. Higher levels of ozone were linked to thicker artery walls, suggesting a potential negative effect, while higher nitrogen dioxide levels were associated with thinner artery walls, a finding that requires further investigation.
Estimating Additive Interaction in Two-Stage Individual Participant Data Meta-Analysis.
The researchers aimed to describe how the Relative Excess Risk due to Interaction (RERI) and other measures of additive interaction or effect modification can be validly estimated within two-stage individual participant data (IPD) meta-analysis. They proposed a three-step procedure to estimate additive interaction, and illustrate this procedure by investigating interaction between depression and smoking and risk of smoking-related cancers incidence during follow-up, and used IPD of six cohorts, including CARTaGENE.
Cohort profile: the CARTaGENE Cohort Nutrition Study (Quebec, Canada)
The researchers aimed to address emerging nutritional epidemiological research questions, using data from the CARTaGENE cohort. Dietary information was collected making it a rich resource for the exploration of diet in the etiology of many health outcomes. They found that dietary intake and quality varied among participants but generally met recommended nutrient levels. Along with other findings, the Canadian Healthy Eating Index 2005 (C-HEI) scores were higher among never smokers, those with higher education, and those with more physical activity compared to current smokers, less than high school education, and those with lower physical activity.
Sex-Specific Associations of Aldosterone and Renin with Body Composition: A Population-Based Cohort Study
The researchers investigated the associations of aldosterone and renin with body composition according to sex in a population-based cohort. Using data from 3,687 adults aged 40-69 years enrolled in the CARTaGENE study, they found that among males, higher aldosterone and renin levels were linked to increased waist to hip ratio, increased fat mass, and decreased lean and muscle mass, while aldosterone specifically was also associated with increased ectopic cardiac adiposity. In contrast, among females higher renin, but not aldosterone, was associated with increased waist circumference, increased waist-to-hip ratio, and increased cardiac adiposity. Higher renin and aldosterone were associated with increased fat mass but were not associated with lean body mass or muscle mass.
Genomic Analysis Identifies Risk Factors in Restless Legs Syndrome
The researchers studied 9,851 Restless Legs Syndrome (RLS) cases and 38,957 controls of European ancestry from CARTaGENE, Canadian Longitudinal Study on Aging, and All of Us biobanks in Canada and the U.S. They found nine genetic locations linked to RLS, including one new location (LMX1B), and identified two related genes (GLO1 and ELFN1). The study also revealed genetic overlaps between RLS and traits like neuroticism, depression, and intelligence. This research enhances our understanding of RLS’s genetic factors.
Addressing dispersion in mis-measured multivariate binomial outcomes: A novel statistical approach for detecting differentially methylated regions in bisulfite sequencing data
The researchers investigated the association between DNA methylation and levels of anti-citrullinated protein antibodies (ACPA), a preclinical marker for rheumatoid arthritis (RA) risk, using asymptomatic samples from the CARTaGENE cohort. Through targeted custom capture sequencing of whole blood, their analysis identified 23 significant genes potentially contributing to ACPA-related differential methylation. These findings emphasize the roles of cell signaling and collagen metabolism in RA.
Investigating the genetic architecture of eye colour in a Canadian cohort
Researchers used data from 5,641 participants of European ancestry from the Canadian Partnership for Tomorrow’s Health (CanPath) and performed genome-wide association studies to investigate the genetic basis of eye color. The study identified multiple independent candidate causal variants in the HERC2/OCA2 region, along with single candidate variants near other genes such as IRF4, SLC24A4, TYR, and TYRP1. These findings suggest that eye color variation is influenced by specific molecular processes in iris melanocytes.
A statistical testing strategy accounting for random and nonrandom (skewed) X-chromosome inactivation identifies lung cancer susceptibility loci among smokers
The research used 9,261 participants from the CARTaGENE cohort to identify susceptibility loci for lung cancer among current and past smokers. X chromosome-wide statistical analysis identified two SNPs in low-linkage disequilibrium located in the IL1RAPL1 (IL-1 R accessory protein-like) gene: rs12558491 and rs12835699. For both SNPs, the minor allele was associated with lower lung cancer risk.