Characterizing Common and Rare Variations in Nontraditional Glycemic Biomarkers Using Multivariate Approaches on Multiancestry ARIC Study.

Genetic studies of nontraditional glycemic biomarkers, glycated albumin and fructosamine, can shed light on unknown aspects of type 2 diabetes genetics and biology. We performed a multiphenotype genome-wide association study of glycated albumin and fructosamine from 7,395 White and 2,016 Black participants in the Atherosclerosis Risk in Communities (ARIC) study on common variants from genotyped/imputed data. We discovered two genome-wide significant loci, one mapping to a known type 2 diabetes gene (ARAP1/STARD10) and another mapping to a novel region (UGT1A complex of genes), using multiomics gene-mapping strategies in diabetes-relevant tissues.

Epigenome-wide association study of incident type 2 diabetes in Black and White participants from the Atherosclerosis Risk in Communities Study.

DNA methylation studies of incident type 2 diabetes in US populations are limited, and to our knowledge none included individuals of African descent living in the US. We performed an epigenome-wide association analysis of blood-based methylation levels at CpG sites with incident type 2 diabetes using Cox regression in 2,091 Black and 1,029 White individuals from the Atherosclerosis Risk in Communities study. At an epigenome-wide significance threshold of 10, we detected 7 novel diabetes-associated CpG sites in (cg05380846: HR= 0.

Characterizing common and rare variations in non-traditional glycemic biomarkers using multivariate approaches on multi-ancestry ARIC study.

Glycated hemoglobin, fasting glucose, glycated albumin, and fructosamine are biomarkers that reflect different aspects of the glycemic process. Genetic studies of these glycemic biomarkers can shed light on unknown aspects of type 2 diabetes genetics and biology. While there exists several GWAS of glycated hemoglobin and fasting glucose, very few GWAS have focused on glycated albumin or fructosamine.

Pleiotropy method reveals genetic overlap between orofacial clefts at multiple novel loci from GWAS of multi-ethnic trios.

Based on epidemiologic and embryologic patterns, nonsyndromic orofacial clefts- the most common craniofacial birth defects in humans- are commonly categorized into cleft lip with or without cleft palate (CL/P) and cleft palate alone (CP), which are traditionally considered to be etiologically distinct. However, some evidence of shared genetic risk in IRF6, GRHL3 and ARHGAP29 regions exists; only FOXE1 has been recognized as significantly associated with both CL/P and CP in genome-wide association studies (GWAS). We used a new statistical approach, PLACO (pleiotropic analysis under composite null), on a combined multi-ethnic GWAS of 2,771 CL/P and 611 CP case-parent trios.