The Italian peninsula has long represented a natural hub for human migrations across
the Mediterranean area, being involved in several prehistoric and historical
population movements. Coupled with a patchy environmental landscape entailing
different ecological/cultural selective pressures, this might have produced peculiar
patterns of population structure and local adaptations responsible for heterogeneous
genomic background of present-day Italians. To disentangle this complex scenario,
genome-wide data from 780 Italian individuals were generated and set into the
context of European/Mediterranean genomic diversity by comparison with genotypes
from 50 populations. To maximize possibility of pinpointing functional genomic
regions that have played adaptive roles during Italian natural history, our survey
included also ~250,000 exomic markers and ~20,000
coding/regulatory variants with well-established clinical relevance. This enabled
fine-grained dissection of Italian population structure through the identification
of clusters of genetically homogeneous provinces and of genomic regions underlying
their local adaptations. Description of such patterns disclosed crucial implications
for understanding differential susceptibility to some inflammatory/autoimmune
disorders, coronary artery disease and type 2 diabetes of diverse Italian
subpopulations, suggesting the evolutionary causes that made some of them
particularly exposed to the metabolic and immune challenges imposed by dietary and
lifestyle shifts that involved western societies in the last centuries.