In:
Communications Biology, Springer Science and Business Media LLC, Vol. 5, No. 1 ( 2022-07-28)
Abstract:
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 whole genome sequencing analyses from fifteen cohorts in NHLBI’s Trans-Omics for Precision Medicine (TOPMed) program. Over 23,000 non-diabetic individuals from five race-ethnicities/populations (African, Asian, European, Hispanic and Samoan) were included. Eight variants were significantly associated with FG or FI across previously identified regions MTNR1B, G6PC2, GCK, GCKR and FOXA2 . We additionally characterize suggestive associations with FG or FI near previously identified SLC30A8, TCF7L2 , and ADCY5 regions as well as APOB, PTPRT , and ROBO1 . Functional annotation resources including the Diabetes Epigenome Atlas were compiled for each signal (chromatin states, annotation principal components, and others) to elucidate variant-to-function hypotheses. We provide a catalog of nucleotide-resolution genomic variation spanning intergenic and intronic regions creating a foundation for future sequencing-based investigations of glycemic traits.
Type of Medium:
Online Resource
ISSN:
2399-3642
DOI:
10.1038/s42003-022-03702-4
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2022
detail.hit.zdb_id:
2919698-X