Jia W. Tan

Pathogenic variants in cardiomyopathy genes confer substantial disease risk, yet clinical penetrance varies widely. The population-level prevalence, age-specific penetrance, and the extent to which polygenic susceptibility modifies disease risk across diverse ancestries remain poorly defined. This population-based cohort study leveraged genome sequencing and linked electronic health record data from the All of Us Research Program (n=414,830). This study found that P/LP variants in cardiomyopathy-associated genes were present in 0.91% of participants (95% CI, 0.88%–0.94%), with similar prevalence across ancestry groups. Compared with non-carriers, variant carriers had significantly higher odds of all-cause heart failure (ACHF, OR, 2.58; 95% CI, 2.31–2.89), non-ischemic heart failure (NIHF, OR, 2.74; 95% CI, 2.42–3.10), and non-ischemic cardiomyopathy (NICM, OR, 4.99; 95% CI, 4.44–5.63). Among carriers, by age 50 years, 24.5% (95% CI, 14.5%–33.4%) developed ACHF, 17.2% (95% CI, 8.8%–24.8%) developed NIHF, and 30.1% (95% CI, 19.5%–40.2%) developed NICM. Higher polygenic risk for heart failure was independently associated with increased risk of ACHF (OR, 1.81; 95% CI, 1.74–1.89), NIHF (OR, 1.66; 95% CI, 1.58–1.75), and NICM (OR, 1.69; 95% CI, 1.59–1.80). Among carriers with elevated polygenic risk, odds of disease were substantially higher than among non-carriers at average polygenic risk (ACHF: OR, 4.71; 95% CI, 4.17–5.32; NIHF: OR, 4.56; 95% CI, 3.99–5.22; NICM: OR, 8.51; 95% CI, 7.44–9.73). Results showed that P/LP variants in cardiomyopathy genes were relatively common in this large, ancestrally diverse cohort, and conferred increased risk of cardiomyopathy and HF, with incomplete but clinically meaningful penetrance. Polygenic risk for HF independently and additively increased disease risk across ancestries. Integrating both may improve risk stratification and enable more precise, equitable care.

DNA methylation is an essential epigenetic modification that plays a crucial role in regulating gene expression and maintaining genomic stability. With the advancement in sequencing technology, methylation studies have provided valuable insights into the diagnosis of rare diseases through the various identification of episignatures, epivariation, epioutliers, and allele-specific methylation. However, current methylation studies are not without limitations. This mini-review explores the current understanding of DNA methylation in rare diseases, highlighting the key mechanisms and diagnostic potential, and emphasizing the need for advanced methodologies and integrative approaches to enhance the understanding of disease progression and design more personable treatment for patients, given the nature of rare diseases.

Climate change is expected to increase the occurrence of extreme environmental conditions. Viticulture, as agriculture in general, is highly dependent on climatic conditions, not only for yield but also for fruit quality, which is the most important factor affecting produce value at the farm-gate. This demands the development of novel plant breeding techniques that will lead to the accelerated production of more resilient grape varieties, as conventional breeding programs for perennials are often prolonged. Recent research has suggested that environmental conditions can activate a memory of stress that could result in a primed response to subsequent stress events. This is a process capable of increasing plant’s resilience to abiotic stimuli, allowing plants to better adapt to extreme environmental conditions. While the effect of priming has been observed in many plants, the underlying mechanisms are puzzling and seldom studied in perennial crops. A large body of research has been developed in the last decade linking response to stress, stress priming, and memory of stress with epigenetic mechanisms. This understanding of plant epigenetics has opened the door to the application of epigenetics to crop improvement, such as the use of epigenetic breeding for the generation of more resilient crops. Perennial crop agriculture in general, and viticulture in particular, would benefit from more in-depth knowledge on epigenetic memory of stress.

Industrial hemp (Cannabis sativa L.) is experiencing a resurgence in North America as an agricultural commodity. Germplasm improvement for locally adapted and stable cannabinoid production is an industry priority. This study used seed priming and pericarp removal to recover seedlings in low-germinating seed lots that could prove important for plant breeding and germplasm conservation. Both seed priming and pericarp removal improved early seed germination, but pericarp removal was more effective in improving overall final germination percentages. On average, pericarp removal improved final germination in low-germinating seed lots by approximately 38% compared to intact seed germination. In seeds with the pericarp removed, the initial germination substrate had an impact on normal seedling development following transplanting: those germinated for 2 to 3 days on rolled towels produced more normal seedlings compared to those started in Petri dishes. There was a dramatic increase in abnormal seedlings produced in the low-germinating seed lot initially germinated in a Petri dish wetted with 6 mL water where nearly 80% never transitioned to normal actively growing seedlings.