An Overview of the Genetic Structure within the Italian Population from Genome-Wide Data

Cornelia Di Gaetano,Nicola Glorioso,Cristina Barlassina,Irma Dianzani,Fabio Rosa,Anna Maria Di Blasio,Marta Betti,Giuseppe Matullo,Francesca Frau,Alberto Piazza,Daniele Cusi,Corrado Magnani,Stefano Bonassi,Giovanni Fiorito,Simonetta Guarrera,Floriana Voglino,Paola Manzini,Dario Mirabelli

doi:10.1371/journal.pone.0043759

Abstract

In spite of the common belief of Europe as reasonably homogeneous at genetic level, advances in high-throughput genotyping technology have resolved several gradients which define different geographical areas with good precision. When Northern and Southern European groups were considered separately, there were clear genetic distinctions. Intra-country genetic differences were also evident, especially in Finland and, to a lesser extent, within other European populations. Here, we present the first analysis using the 125,799 genome-wide Single Nucleotide Polymorphisms (SNPs) data of 1,014 Italians with wide geographical coverage. We showed by using Principal Component analysis and model-based individual ancestry analysis, that the current population of Sardinia can be clearly differentiated genetically from mainland Italy and Sicily, and that a certain degree of genetic differentiation is detectable within the current Italian peninsula population. Pair-wise FST statistics Northern and Southern Italy amounts approximately to 0.001 between, and around 0.002 between Northern Italy and Utah residents with Northern and Western European ancestry (CEU). The Italian population also revealed a fine genetic substructure underscoring by the genomic inflation (Sardinia vs. Northern Italy = 3.040 and Northern Italy vs. CEU = 1.427), warning against confounding effects of hidden relatedness and population substructure in association studies.

Highlights

Genetic gradients are represented by continuous differences in allele frequencies created by events such as gene flow between two different populations, or by a demographic expansion into a scarcely populated environment, leading to a partial admixture with indigenous populations, genetic drift or differential selection [1]
Principal component analysis of the Italian population The eigenvectors for different subsets (HGDP-CEPH data, HapMap CEU and Tuscany data) were calculated in order to project the Italian data sets onto a two dimensional space (Figure 1) using 125,799 autosomal Single Nucleotide Polymorphisms (SNPs)
The position of the Italian population samples suggests that genetic distances between these populations and other European and Middle East populations has a good correlation with geographic distances

Summary

Introduction

Genetic gradients are represented by continuous differences in allele frequencies created by events such as gene flow between two different populations, or by a demographic expansion into a scarcely populated environment, leading to a partial admixture with indigenous populations, genetic drift or differential selection [1]. These differences in allele frequencies may generate population stratification, which is an important confounding factor in genetic association studies [2]. Genetically homogeneous populations do not always coincide with the ‘political’ definition of a country, but a recent paper has shown that clinal patterns in principal component analysis (PC) probably develop due to a simple isolation-by-distance process [21]

Methods

Results

Conclusion