Weale, M. E. | bioRxiv Science

bioRxiv2017

The genetic legacy of Zoroastrianism in Iran and India: Insights into population structure, gene flow and selection.

Zoroastrianism is one of the oldest extant religions in the world, originating in Persia (present-day Iran) during the second millennium BCE. Historical records indicate that migrants from Persia brought Zoroastrianism to India, but there is debate over the timing of these migrations. Here we present novel genome-wide autosomal, Y-chromosome and mitochondrial data from Iranian and Indian Zoroastrians and neighbouring modern-day Indian and Iranian populations to conduct the first genome-wide genetic analysis in these groups. Using powerful haplotype-based techniques, we show that Zoroastrians in Iran and India show increased genetic homogeneity relative to other sampled groups in their respective countries, consistent with their current practices of endogamy. Despite this, we show that Indian Zoroastrians (Parsis) intermixed with local groups sometime after their arrival in India, dating this mixture to 690-1390 CE and providing strong evidence that the migrating group was largely comprised of Zoroastrian males. By exploiting the rich information in DNA from ancient human remains, we also highlight admixture in the ancestors of Iranian Zoroastrians dated to 570 BCE-746 CE, older than admixture seen in any other sampled Iranian group, consistent with a long-standing isolation of Zoroastrians from outside groups. Finally, we report genomic regions showing signatures of positive selection in present-day Zoroastrians that might correlate to the prevalence of particular diseases amongst these communities.

genomics↗

bioRxiv2016

True causal effect size heterogeneity is required to explain trans-ethnic differences in GWAS signals

Through genome-wide association studies (GWASs), researchers have identified hundreds of genetic variants associated with particular complex traits. Previous studies have compared the pattern of association signals across different populations in real data, and these have detected differences in the strength and sometimes even the direction of GWAS signals. These differences could be due to a combination of (1) lack of power (insufficient sample sizes); (2) minor allele frequency (MAF) differences (again affecting power); (3) linkage disequilibrium (LD) differences (affecting power to tag the causal variant); and (4) true differences in causal variant effect sizes (defined by relative risks).\n\nIn the present work, we sought to assess whether the first three of these reasons are sufficient on their own to explain the observed incidence of trans-ethnic differences in replications of GWAS signals, or whether the fourth reason is also required. We simulated case-control data of European, Asian and African ancestry, drawing on observed MAF and LD patterns seen in the 1000-Genomes reference dataset and assuming the true causal relative risks were the same in all three populations.\n\nWe found that a combination of Euro-centric SNP selection and between-population differences in LD, accentuated by the lower SNP density typical of older GWAS panels, was sufficient to explain the rate of trans-ethnic differences previously reported, without the need to assume between-population differences in true causal SNP effect size. This suggests a cross-population consistency that has implications for our understanding of the interplay between genetics and environment in the aetiology of complex human diseases.

genomics↗