An Integrative Phenotype-Genotype Approach Using Phenotypic Characteristics from the UAE National Diabetes Study Identifies as a Candidate Gene for Obesity and Type 2 Diabetes.HSD17B12

Mahmood Y Hachim; Hayat Aljaibeji; Rifat A Hamoudi; Ibrahim Y Hachim; Noha M Elemam; Abdul Khader Mohammed; Albert Salehi; Jalal Taneera; Nabil Sulaiman
Abstract
The United Arab Emirates National Diabetes and Lifestyle Study (UAEDIAB) has identified obesity, hypertension, obstructive sleep apnea, and dyslipidemia as common phenotypic characteristics correlated with diabetes mellitus status. As these phenotypes are usually linked with genetic variants, we hypothesized that these phenotypes share single nucleotide polymorphism (SNP)-clusters that can be used to identify causal genes for diabetes. Materials and We explored the National Human Genome Research Institute-European Bioinformatics Institute Catalog of Published Genome-Wide Association Studies (NHGRI-EBI GWAS) to list SNPs with documented association with the UAEDIAB-phenotypes as well as diabetes. The shared chromosomal regions affected by SNPs were identified, intersected, and searched for Enriched Ontology Clustering. The potential SNP-clusters were validated using targeted DNA next-generation sequencing (NGS) in two Emirati diabetic patients. RNA sequencing from human pancreatic islets was used to study the expression of identified genes in diabetic and non-diabetic donors. Eight chromosomal regions containing 46 SNPs were identified in at least four out of the five UAEDIAB-phenotypes. A list of 34 genes was shown to be affected by those SNPs. Targeted NGS from two Emirati patients confirmed that the identified genes have similar SNP-clusters. , and genes showed the highest SNPs rate among the identified genes. RNA-seq analysis revealed high expression levels of in human islets and to be upregulated in type 2 diabetes (T2D) donors. Our integrative phenotype-genotype approach is a novel, simple, and powerful tool to identify clinically relevant potential biomarkers in diabetes. is a novel candidate gene for pancreatic β-cell function.ASAH1, LRP4, FES
Journal GENES
ISSN 2073-4425
Published 23 Apr 2020
Volume 11
Issue 4
Pages
DOI 10.3390/genes11040461
Type Journal Article
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