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Article
Adaptive selection at G6PD and disparities in diabetes complications
Diabetes complications occur at higher rates in individuals of African ancestry. Glucose-6-phosphate dehydrogenase deficiency (G6PDdef), common in some African populations, confers malaria resistance, and redu...
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Article
Open AccessVariant level heritability estimates of type 2 diabetes in African Americans
Type 2 diabetes (T2D) is caused by both genetic and environmental factors and is associated with an increased risk of cardiorenal complications and mortality. Though disproportionately affected by the conditio...
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Article
Open AccessPolygenic scores for longitudinal prediction of incident type 2 diabetes in an ancestrally and medically diverse primary care physician network: a patient cohort study
The clinical utility of genetic information for type 2 diabetes (T2D) prediction with polygenic scores (PGS) in ancestrally diverse, real-world US healthcare systems is unclear, especially for those at low cli...
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Article
Open AccessGenetic drivers of heterogeneity in type 2 diabetes pathophysiology
Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic c...
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Article
Open AccessSelection, optimization and validation of ten chronic disease polygenic risk scores for clinical implementation in diverse US populations
Polygenic risk scores (PRSs) have improved in predictive performance, but several challenges remain to be addressed before PRSs can be implemented in the clinic, including reduced predictive performance of PRS...
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Article
Open AccessMulti-tissue epigenetic analysis identifies distinct associations underlying insulin resistance and Alzheimer’s disease at CPT1A locus
Insulin resistance (IR) is a major risk factor for Alzheimer’s disease (AD) dementia. The mechanisms by which IR predisposes to AD are not well-understood. Epigenetic studies may help identify molecular signat...
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Article
Open AccessPrecision subclassification of type 2 diabetes: a systematic review
Heterogeneity in type 2 diabetes presentation and progression suggests that precision medicine interventions could improve clinical outcomes. We undertook a systematic review to determine whether strategies to...
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Article
Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes ...
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Article
Open AccessGWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification
Conventional measurements of fasting and postprandial blood glucose levels investigated in genome-wide association studies (GWAS) cannot capture the effects of DNA variability on ‘around the clock’ glucoregula...
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Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin ac...
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Article
A framework for detecting noncoding rare-variant associations of large-scale whole-genome sequencing studies
Large-scale whole-genome sequencing studies have enabled analysis of noncoding rare-variant (RV) associations with complex human diseases and traits. Variant-set analysis is a powerful approach to study RV ass...
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Article
A combined polygenic score of 21,293 rare and 22 common variants improves diabetes diagnosis based on hemoglobin A1C levels
Polygenic scores (PGSs) combine the effects of common genetic variants1,2 to predict risk or treatment strategies for complex diseases3–7. Adding rare variation to PGSs has largely unknown benefits and is methodi...
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Open AccessPatient and provider perspectives on polygenic risk scores: implications for clinical reporting and utilization
Polygenic risk scores (PRS), which offer information about genomic risk for common diseases, have been proposed for clinical implementation. The ways in which PRS information may influence a patient’s health t...
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Article
Open AccessLeveraging family history in genetic association analyses of binary traits
Considering relatives’ health history in logistic regression for case–control genome-wide association studies (CC-GWAS) may provide new information that increases accuracy and power to detect disease associate...
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Article
Open AccessWhole genome sequence association analysis of fasting glucose and fasting insulin levels in diverse cohorts from the NHLBI TOPMed program
The genetic determinants of fasting glucose (FG) and fasting insulin (FI) have been studied mostly through genome arrays, resulting in over 100 associated variants. We extended this work with high-coverage who...
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Article
Open AccessProteomic analysis of cardiometabolic biomarkers and predictive modeling of severe outcomes in patients hospitalized with COVID-19
The high heterogeneity in the symptoms and severity of COVID-19 makes it challenging to identify high-risk patients early in the disease. Cardiometabolic comorbidities have shown strong associations with COVID...
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Article
Genome-wide polygenic score to predict chronic kidney disease across ancestries
Chronic kidney disease (CKD) is a common complex condition associated with high morbidity and mortality. Polygenic prediction could enhance CKD screening and prevention; however, this approach has not been opt...
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Article
Open AccessDevelopment and validation of a trans-ancestry polygenic risk score for type 2 diabetes in diverse populations
Type 2 diabetes (T2D) is a worldwide scourge caused by both genetic and environmental risk factors that disproportionately afflicts communities of color. Leveraging existing large-scale genome-wide association...
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Article
A multiancestry genome-wide association study of unexplained chronic ALT elevation as a proxy for nonalcoholic fatty liver disease with histological and radiological validation
Nonalcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver disease. Using a proxy NAFLD definition of chronic elevation of alanine aminotransferase (cALT) levels without other liver diseases,...
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Article
Open AccessAssociation between muscle mass and diabetes prevalence independent of body fat distribution in adults under 50 years old
Although relatively less muscle mass has been associated with greater diabetes prevalence, whether there is an association between muscle mass and diabetes prevalence independent of body fat distribution is un...
