Publications by authors named "Jonathan Z Luo"
Importance: Most studies of autosomal dominant polycystic kidney disease (ADPKD) genetics have used kidney specialty cohorts, focusing on PKD1 and PKD2. These can lead to biased estimates of population prevalence of ADPKD-associated gene variants and their phenotypic expression.
Objective: To determine the prevalence of ADPKD and contributions of PKD1, PKD2, and other genes related to cystic kidney disease in a large, unselected cohort.
Body fat distribution is a major, heritable risk factor for cardiometabolic disease, independent of overall adiposity. Using exome-sequencing in 618,375 individuals (including 160,058 non-Europeans) from the UK, Sweden and Mexico, we identify 16 genes associated with fat distribution at exome-wide significance. We show 6-fold larger effect for fat-distribution associated rare coding variants compared with fine-mapped common alleles, enrichment for genes expressed in adipose tissue and causal genes for partial lipodystrophies, and evidence of sex-dimorphism.
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- Genetic testing in individuals without symptoms can reveal carriers of harmful arrhythmia gene variants, but the clinical implications of these findings are still not fully understood.
- In a study of nearly 22,000 participants, 0.6% were found to carry pathogenic or likely pathogenic variants linked to arrhythmias, with many displaying significant arrhythmia-related health records.
- Follow-up investigations showed that variant results led to new diagnoses in some individuals, highlighting the potential for genome sequencing to uncover important health information.
Purpose: Genetic variation in MC1R is a main determinant of red hair color (RHC) phenotype and confers susceptibility to skin disorders.
Methods: We assessed the effects and function of MC1R variants identified in our clinical cohort of 135,947 participants with available exome sequencing using phenome-wide association scan (PheWAS). Expression and function of several variants were evaluated.
Background: Empirical data on conditions that increase risk of coronavirus disease 2019 (COVID-19) progression are needed to identify high risk individuals. We performed a comprehensive quantitative assessment of pre-existing clinical phenotypes associated with COVID-19-related hospitalization.
Methods: Phenome-wide association study (PheWAS) of SARS-CoV-2-positive patients from an integrated health system (Geisinger) with system-level outpatient/inpatient COVID-19 testing capacity and retrospective electronic health record (EHR) data to assess pre-COVID-19 pandemic clinical phenotypes associated with hospital admission (hospitalization).
Article Synopsis
- - This study focuses on identifying genetic mutations related to autosomal dominant polycystic kidney disease (ADPKD), highlighting the role of a newly discovered gene that affects the production of a crucial protein, polycystin-1 (PC1), which is essential for kidney function.
- - Researchers used whole-exome sequencing on 122 patients to find mutations and conducted cell-based assays to confirm how these mutations impair PC1's production and function, leading to kidney cyst formation.
- - The findings indicate that this novel gene plays a significant role in the complex genetics of ADPKD, emphasizing the importance of linking genetic information with observable disease traits for better understanding and potential treatments.
Purpose: Precision health initiatives and reduced sequencing costs are driving large-scale human genome analyses. Genetic variant curation is a bottleneck in clinical applications. The burden of variant curation can be high for newly discovered variants because they are less likely to have undergone previous clinical annotation; the rate of discovery of genetic variants in large clinical populations has not been empirically determined.
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- The study aims to investigate the potential health risks associated with rare genetic variants linked to sudden infant death syndrome (SIDS) by examining their effects on cardiac function.
- Researchers identified nine specific variants through genetic testing of 292 SIDS cases, performing various analyses to compare the functional properties of these variants with normal cardiac channels.
- Results indicate that most of the identified variants display normal channel behavior and do not significantly affect heart function, suggesting they are not related to long-QT syndrome subtype 2.
Background: Elucidation of the genetic factors underlying chronic liver disease may reveal new therapeutic targets.
Methods: We used exome sequence data and electronic health records from 46,544 participants in the DiscovEHR human genetics study to identify genetic variants associated with serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Variants that were replicated in three additional cohorts (12,527 persons) were evaluated for association with clinical diagnoses of chronic liver disease in DiscovEHR study participants and two independent cohorts (total of 37,173 persons) and with histopathological severity of liver disease in 2391 human liver samples.