JACC Focus Seminar: Obesity, Diabetes, And Phenotypes
JACC Focus Seminar
Genetics of Type 2 Diabetes: Opportunities for Precision Medicine: JACC Focus Seminar

https://doi.org/10.1016/j.jacc.2021.03.346Get rights and content
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Highlights

  • The association of T2D with CVD accounts for substantial morbidity and mortality.

  • Genetic associations delineate mechanistic pathways influencing T2D phenotypes with implications for pathogenesis and treatment.

  • Further work is needed to characterize these genetic links across diverse ancestries.

Abstract

Type 2 diabetes (T2D) is highly prevalent and is a strong contributor for cardiovascular disease. However, there is significant heterogeneity in disease pathogenesis and the risk of complications. Enormous progress has been made in our ability to catalog genetic variation associated with T2D risk and variation in disease-relevant quantitative traits. These discoveries hold the potential to shed light on tractable targets and pathways for safe and effective therapeutic development, but the promise of precision medicine has been slow to be realized. Recent studies have identified subgroups of individuals with differential risk for intermediate phenotypes (eg, lipid levels, fasting insulin, body mass index) that contribute to T2D risk, helping to account for the observed clinical heterogeneity. These “partitioned genetic risk scores” not only have the potential to identify patients at greatest risk of cardiovascular disease and rapid disease progression, but also could aid patient stratification bridging the gap toward precision medicine for T2D.

Key Words

genetics
precision medicine
type 2 diabetes

Abbreviations and Acronyms

BMI
body mass index
CVD
cardiovascular disease
eQTL
expression quantitative trait locus
GWAS
genome-wide association study
HbA1c
hemoglobin A1c
MR
Mendelian randomization
NAFLD
nonalcoholic fatty liver disease
PheWAS
phenome-wide association study
PRS
polygenic risk score
T2D
type 2 diabetes

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