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As humans spread out of Africa they encountered a wide range of different environments and ecosystems, to which they may have been under selective pressure to adapt. Several studies have found immune and defense related genes to have been under positive selection in human evolution. However, little is known about the degree to which adaptation to local environment is primarily related to pathogens, or if most local adaptation is in response to other local environmental conditions. By correlating genetic variation of more than 50 human populations with a set of environmental variables, we identified signatures of human local genetic adaptation. We showed that while majority of human variation can be explained by neutral factors, several loci show signatures of natural selection and this effect is mostly explained by adaptation to pathogen environment. Detecting loci under natural selection owing to local adaptation may help addressing evolutionary history of modern complex diseases and optimize further designs of disease association studies to better unveil relationship between mutation and disorder susceptibility