# CNV Analysis Associates AKNAD1 with Type-2 Diabetes in Jordan Subpopulations

## TL;DR

This study identifies a copy number variation in the AKNAD1 gene linked to type-2 diabetes in Jordanian subpopulations.

## Contribution

The first CNV analysis of type-2 diabetes in Jordanian populations, identifying AKNAD1 as a novel association.

## Key findings

- A CNV region in PTPRD was significantly associated with type-2 diabetes.
- A CNV in AKNAD1 surpassed the experiment-wide significance threshold for T2D.
- ER-related pathways were enriched in genes functionally linked to AKNAD1.

## Abstract

Previous studies have identified a number of single nucleotide polymorphisms (SNPs) associated with type-2 diabetes (T2D), but copy number variation (CNV) association has rarely been addressed, especially in populations from Jordan. To investigate CNV associations for T2D in populations in Jordan, we conducted a CNV analysis based on intensity data from genome-wide SNP array, including 34 T2D cases and 110 healthy controls of Chechen ethnicity, as well as 34 T2D cases and 106 healthy controls of Circassian ethnicity. We found a CNV region in protein tyrosine phosphatase receptor type D (PTPRD) with significant association with T2D. PTPRD has been reported to be associated with T2D in genome-wide association studies (GWAS). We additionally identified 16 CNV regions associated with T2D which overlapped with gene exons. Of particular interest, a CNV region in the gene AKNA Domain Containing 1 (AKNAD1) surpassed the experiment-wide significance threshold. Endoplasmic reticulum (ER)-related pathways were significantly enriched among genes which are predicted to be functionally associated with human or mouse homologues of AKNAD1. This is the first CNV analysis of a complex disease in populations of Jordan. We identified and experimentally validated a significant CNVR in gene AKNAD1 associated with T2D.