Previous genome-wide scans of positive natural selection in humans have 
identified a number of non-neutrally evolving genes that play important roles in 
skin pigmentation, metabolism, or immune function. Recent studies have also 
shown that a genome-wide pattern of local adaptation can be detected by 
identifying correlations between patterns of allele frequencies and 
environmental variables. Despite these observations, the degree to which natural 
selection is primarily driven by adaptation to local environments, and the role 
of pathogens or other ecological factors as selective agents, is still under 
debate. To address this issue, we correlated the spatial allele frequency 
distribution of a large sample of SNPs from 55 distinct human populations to a 
set of environmental factors that describe local geographical features such as 
climate, diet regimes, and pathogen loads. In concordance with previous studies, 
we detected a significant enrichment of genic SNPs, and particularly 
non-synonymous SNPs associated with local adaptation. Furthermore, we show that 
the diversity of the local pathogenic environment is the predominant driver of 
local adaptation, and that climate, at least as measured here, only plays a 
relatively minor role. While background demography by far makes the strongest 
contribution in explaining the genetic variance among populations, we detected 
about 100 genes which show an unexpectedly strong correlation between allele 
frequencies and pathogenic environment, after correcting for demography. 
Conversely, for diet regimes and climatic conditions, no genes show a similar 
correlation between the environmental factor and allele frequencies. This result 
is validated using low-coverage sequencing data for multiple populations. Among 
the loci targeted by pathogen-driven selection, we found an enrichment of genes 
associated to autoimmune diseases, such as celiac disease, type 1 diabetes, and 
multiples sclerosis, which lends credence to the hypothesis that some 
susceptibility alleles for autoimmune diseases may be maintained in human 
population due to past selective processes.