The genetics of risk in type 2 diabetes mellitus : does whole exome sequencing of pooled DNA identify population-specific risk alleles?

Abstract

Type 2 Diabetes Mellitus T2DM is a common disorder in the population of the Mediterranean region. The aim of this study was to address the issue of genetic risk in T2DM as part of a long-term project following two lines of investigation. Firstly, by mapping selective panels with cognate loci, and secondly by searching for additional genetic risk alleles among the genomes of three comparative neighbouring populations from the central Mediterranean (Maltese, Italian and Libyan). Innovative Pool-seq was used to improve the efficiency of these studies however there were certain limitations. In particular, though demonstrably strong, it could have benefited from using larger population groups with well-defined ancestry and geographic origins, as well as having more robust objective phenotypes. In this study, data is provided indicating the quantitative combination of 11 risk alleles is significantly linked with an increase in the risk of developing T2DM in these populations studied. Since an individual genetic variant, is not very informative for evaluating disease risk, the summation of multiple risk alleles was necessary to detect those at high risk. By examining the SNV data, this study has demonstrated, that the genetic relatedness of European populations such as Maltese, Italian and the North African Libyan population are quite closely linked. It is interesting to note that although the associated variants with known T2DM risk alleles in the three populations are quite similar, the similarities in risk alleles between Maltese and Italians was even stronger than would be expected from their shared ancestry.