Association of parity with the timing and type of menopause: A longitudinal cohort study
The study aimed to determine the time-varying association between parity and timing of natural menopause, surgical menopause, and premenopausal hysterectomy among 23,728 women aged 40-65 years at enrollment in the Alberta’s Tomorrow Project cohort study. The researchers found that overall, natural menopause was most common, then premenopausal hysterectomy and surgical menopause. The risk of natural menopause before age 50 was higher for women with 0 or 1 birth, while the risk was similar for those with 3 or more births compared to those with 2 births. Elevated risks of surgical menopause before age 45 for women with 0 or 1 birth were reduced after excluding those with a history of infertility or recurrent pregnancy loss, and the risk decreased over time for women with 3 or more births. Additionally, the risk of premenopausal hysterectomy before age 50 was lower for women with 0 births but increased after age 40 for those with 3 or more births.
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.
Premature thymic functional senescence is a hallmark of childhood acute lymphoblastic leukemia survivorship
The researchers investigated thymic immunosenescence in childhood acute lymphoblastic leukemia (cALL) survivors. The healthy participant cohort consisted of participants from the CARTaGENE cohort and an institutional cohort from the Centre Hospitalier de l’Université de Montréal. The thymic immunosenescence biomarker, signal joint T-cell receptor excision circles (TREC), was evaluated and was highly correlated with age in healthy participants and cALL survivors. While TREC levels declined with age in both groups, cALL survivors exhibited a systematic immunoage acceleration ranging from 5.9 to 88.3 years. This immunoage gain was independent of age at diagnosis and treatment modalities but was more pronounced in females and those with metabolic syndrome. The decline in TREC was unrelated to blood cell counts, suggesting selective thymic aging.
Early Changes in Tumor-Naive Cell-Free Methylomes and Fragmentomes Predict Outcomes in Pembrolizumab-Treated Solid Tumors
The researchers investigated pharmacodynamic biomarkers of response to pembrolizumab in 106 patients with advanced solid tumors. Researchers analyzed genome-wide methylation and fragment-length profiles using cfMeDIP-seq in 204 plasma samples from 87 patients. Two cohorts of normal control cfMeDIP-seq data, including 72 healthy women from the Ontario Health Study, were used for comparison. CSM and FLS are strongly correlated with tumor-informed ctDNA levels. The study found that early kinetics of cancer-specific methylation (CSM) predicted overall survival and progression-free survival, independent of tumor type, PD-L1, and tumor mutation burden. The researchers’ tumor-naïve mutation-agnostic ctDNA approach integrating methylomics and fragmentomics could predict outcomes in patients treated with pembrolizumab.
Risk factors for early-onset colorectal cancer: A Canadian prospective cohort study
Researchers aimed to determine associations between specific risk factors and early-onset colorectal cancer (eoCRC). Accordingly, the researchers utilized data from 127,852 healthy study participants who were less than 50 years of age and were either part of the Ontario Health Study cohort or the Alberta’s Tomorrow Project cohort. Ninety-eight cases of eoCRC were identified after an average follow-up of 6.63 years. Analyses indicated that a family history of CRC alone or with a history of other cancer types was associated with a heightened risk of developing eoCRC. However, there was no significant association between eoCRC and a family history of solely non-CRC cancer. Those classified as heavy smokers at baseline had a higher risk of eoCRC compared to non-smokers. Lastly, there were no significant associations between sex, socioeconomic factors, diabetes, alcohol consumption, and other factors with the risk of eoCRC.