Characterization of Large Copy Number Variation in Mexican Type 2 Diabetes subjects

Iván De Jesús Ascencio-Montiel,Stephen W Scherer,Dalila Pinto,Miguel Cruz,Esteban J Parra,Adán Valladares-Salgado

doi:10.1038/s41598-017-17361-7

Abstract

The effect of Copy Number Variants (CNVs) on Type 2 Diabetes (T2D) remains little explored. The present study characterized large rare CNVs in 686 T2D and 194 non-T2D subjects of Mexican ancestry genotyped using the Affymetrix Genome-Wide Human SNP array 5.0. Rare CNVs with ≥ 100 kb length were identified using a stringent strategy based on merging CNVs calls generated using Birdsuit, iPattern and PennCNV algorithms. We applied three different strategies to evaluate the distribution of CNVs in the T2D and non-T2D samples: 1) Burden analysis, 2) Identification of CNVs in loci previously associated to T2D, and 3) Identification of CNVs observed only in the T2D group. In the CNV burden analysis, the T2D group showed a higher proportion of CNVs, and also a higher proportion of CNVs overlapping at least one gene than the non T2D group. Five of the six loci previously associated with T2D had duplications or deletions in the T2D sample, but not the non-T2D sample. A gene-set analysis including genes with CNVs observed only in the T2D group highlighted gene-sets related with sensory perception (olfactory receptors, OR) and phenylpyruvate tautomerase/dopachrome isomerase activity (MIF and DDT genes).

Highlights

The current Mexican population is an admixed population with a genetic background derived from European, Native American and to lesser extent, West African populations[8]
We found that the T2D group showed a higher proportion of CNVs overlapping with at least one gene than the control group
In this study conducted in Mexico we found that the T2D group showed a higher proportion of CNVs than the control sample, and a higher proportion of CNVs overlapping at least one gene than the control group

Summary

Introduction

The current Mexican population is an admixed population with a genetic background derived from European, Native American and to lesser extent, West African populations[8]. Mexico has one of the highest prevalences of T2D in the world[9]. We characterized large rare CNVs in T2D and non-T2D individuals (controls) of Mexican ancestry that were genotyped with the Affymetrix 5.0 array[10]. We applied three different strategies in order to evaluate the distribution of CNVs in the T2D and control samples: 1) Burden analysis, 2) Identification of CNVs in loci previously associated to T2D, and 3) Identification of CNVs observed only in the T2D group. Characteristic N General characteristics Male/female sex Age, years BMI, kg/m2 Total cholesterol, mg/dL Triglycerides, mg/dL MDS1 ancestry vector MDS2 ancestry vector MDS3 ancestry vector Rare CNVs Number of Rare CNVs Deletions Duplications CNVs size in Mb Deletions Duplications Genic Rare CNVs Number of Genic Rare CNVs Deletions Duplications CNVs size in Mb Deletions Duplications

Methods

Results

Conclusion