PT - JOURNAL ARTICLE AU - Emily S Wong AU - Joseph E Powell TI - Allelic differentiation of complex trait loci across human populations AID - 10.1101/126888 DP - 2017 Jan 01 TA - bioRxiv PG - 126888 4099 - http://biorxiv.org/content/early/2017/04/12/126888.short 4100 - http://biorxiv.org/content/early/2017/04/12/126888.full AB - The genetic basis for differences between humans lies at those DNA bases that vary between individuals. Comparative genomics is a powerful tool for dissecting the functions of genomes by comparing the genomes of divergent organisms to identify functional regions. However, much of the functional signals in mammalian genomes are non-coding and evolving rapidly leading to population-specific differences. Here, we use a sensitive genome-wide measure of human genetic differentiation between global populations to detect differences associated with complex traits. Highly differentiated genomic regions were associated with regulatory elements and morphological features. We observed variation in allelic differentiation between populations at tissue-specific expression quantitative trait loci (eQTL), with greatest effects found for genes expressed in a region of the brain that has been linked to schizophrenia and bipolar disorder. Consistent with this, genome-wide association study regions also showed high levels of population differentiation for these diseases suggesting that loci linked to neurological function evolve rapidly. Clear differences for genetic structure in populations were observed for closely related complex human phenotypes. We show that the evolutionary forces acting at pleiotropic loci are often neutral by comparing directional effects of traits under selection. Our results illustrate the value of within species comparisons to understanding complex trait evolution.Author Summary Differences in genome sequence, both within and between populations, are linked to a wide spectrum of morphological, physiological and behavioral differences between humans. Many of these observed differences are considered ‘complex’ – meaning that they are encoded in the genome at many locations. By comparing variation in DNA bases between populations, to genomic regions for complex traits, we can gain insights into differences in the evolutionary trajectory of different types of complex traits. Here, we use a sensitive method to quantitate genetic differences between the major human populations. Although certain diseases are closely related, they can show distinct patterns of genetic differentiation between populations. Certain regions of the genome are more distinct between populations, including regulatory regions, particularly those linked to changes in the number of genes expressed in the brain, and those involved in types of neurological disease.