Variant level heritability estimates of type 2 diabetes in African Americans

• Published in: Scientific reports 2024-06, Vol.14 (1), p.14009-9, Article 14009
• Main Authors: Armstrong, Nicole D., Patki, Amit, Srinivasasainagendra, Vinodh, Ge, Tian, Lange, Leslie A., Kottyan, Leah, Namjou, Bahram, Shah, Amy S., Rasmussen-Torvik, Laura J., Jarvik, Gail P., Meigs, James B., Karlson, Elizabeth W., Limdi, Nita A., Irvin, Marguerite R., Tiwari, Hemant K.
• Format: Article
• Language: English
• Subjects: 631/208/729; 692/308/2056; 692/699/2743/137/773; 692/700/3935; African Americans; Aged; Black or African American - genetics; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - genetics; Disparities; Electronic medical records; Environmental factors; Female; Genetic polymorphisms; Genetic Predisposition to Disease; Genetics; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genomic analysis; Genomics; Heritability; Heritable quantitative trait; Humanities and Social Sciences; Humans; Hypertension; Linkage Disequilibrium; Male; Middle Aged; Minority & ethnic groups; multidisciplinary; Multifactorial Inheritance - genetics; Phenotype; Polymorphism, Single Nucleotide; Science; Science (multidisciplinary); Type 2 diabetes mellitus
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-64711-3

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 condition, African Americans (AA) are largely underrepresented in genetic studies of T2D, and few estimates of heritability have been calculated in this race group. Using genome-wide association study (GWAS) data paired with phenotypic data from ~ 19,300 AA participants of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, Genetics of Hypertension Associated Treatments (GenHAT) study, and the Electronic Medical Records and Genomics (eMERGE) network, we estimated narrow-sense heritability using two methods: Linkage-Disequilibrium Adjusted Kinships (LDAK) and Genome-Wide Complex Trait Analysis (GCTA). Study-level heritability estimates adjusting for age, sex, and genetic ancestry ranged from 18% to 34% across both methods. Overall, the current study narrows the expected range for T2D heritability in this race group compared to prior estimates, while providing new insight into the genetic basis of T2D in AAs for ongoing genetic discovery efforts.