Endophenotypes are critical biological markers with genetic links to disease progression. We previously developed endoPRS, a multi-trait polygenic risk score (PRS) method that leverages endophenotype data to improve disease risk prediction. However, endoPRS requires individual-level genotype-phenotype data for model fitting, restricting its broader use. To address this, we introduce endoPRS-SS, an extension which enables PRS inference using genome-wide association study (GWAS) summary statistics...

Obstructive sleep apnea (OSA) is a prevalent chronic respiratory condition characterized by repetitive upper airway collapse during sleep, leading to transient hypoxemia and arousals from sleep. Multiple risk factors heighten susceptibility to OSA. Intermittent hypoxia caused by OSA can increase the risk of end-organ morbidity. Key mechanisms include mitochondrial dysfunction, excessive production of ROS, and inflammation driven by NF-κB. HIF-1α responses vary by tissue and exposure pattern and may be attenuated during chronic intermittent hypoxia.

Using a broad panel of ciliopathy iPSC-retinal pigment epithelium (RPE) new approach models, Reichert et al. identified shared cellular endophenotypes across patients, including mesenchymal drift and loss of polarization. Mechanistic studies implicated mitochondrial dysfunction and aberrant TGF-β signaling in RPE pathology. Drug screening identified pioglitazone and galunisertib as candidate therapeutics.

Obstructive sleep apnea (OSA) is a prevalent chronic respiratory condition characterized by repetitive upper airway collapse during sleep, leading to transient hypoxemia and arousals from sleep. Multiple risk factors heighten susceptibility to OSA. Intermittent hypoxia caused by OSA can increase the risk of end-organ morbidity. Key mechanisms include mitochondrial dysfunction, excessive production of ROS, and inflammation driven by NF-κB. HIF-1α responses vary by tissue and exposure pattern and may be attenuated during chronic intermittent hypoxia.

Association of GLP1R locus with mental ill-health endophenotypes and cardiometabolic traits: A trans-ancestry study in UK Biobank. Diabetes, ... View article...

Deep learning image embeddings enable scalable GWAS of complex dog phenotypes.

Chronic obstructive pulmonary disease (COPD) and heart failure with preserved ejection fraction (HFpEF) are two of the leading causes of mortality worldwide (1). The complexity of these diseases is highlighted by the significant overlap in their patient populations; more than one-third of individuals hospitalized for heart failure exacerbations also have COPD, and the inverse is similarly true (2). This intersection not only complicates clinical diagnosis but also blurs the lines in management strategies. The echocardiographic findings that characterize both conditions—often with shared markers such as impaired left ventricular (LV) filling—further add to the challenge, potentially leading to mismanagement, prolonged hospital stays, and ultimately poorer patient outcomes.

Han et al. identify H1β1γ1, a structural haplotype in the 17q21.31 region that contains MAPT, as a genetic risk factor for CTE neuropathological and clinical endophenotypes. H1β1γ1 DGE analyses in the dorsolateral frontal cortex implicate cis-acting genes and inflammatory pathways. H1β1γ1 may help explain CTE risk beyond repetitive head impact exposure.