Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005

Ancient DNA research is revealing a human history far more complex than that inferred from parsimonious models based on modern DNA. Here, we review some of the key events in the peopling of the world in the light of the findings of work on ancient DNA.

Highlights d The Uganda Genome Resource comprises genetic and phenotypic data on 6,400 individuals d Ugandans show geographically correlated genetic substructure and complex admixture d The Uganda sequence panel substantially improves imputation in African populations d The Uganda Genome Resource enables novel discovery of loci associated with traits

Although diverse biological disciplines employ the nematode Caenorhabditis elegans as a highly efficient laboratory model system, little is known about its natural history. We investigated its evolutionary past using 10 polymorphic trinucleotide and tetranucleotide microsatellites, derived from across the whole genome. These microsatellites were analyzed from the 35 previously available natural isolates from different parts of the world and also 23 new strains isolated from northwest Germany. Our results highlight that C. elegans lineages differentiate genetically with respect to geographic distance and, to a lesser extent, differences in the time of strain isolation. The latter indicates some turnover of strain genotypes at specific locations. Our data also demonstrate the coexistence of highly diverse genotypes in the population from northwest Germany, which is best explained by recent migration events. Furthermore, selfing is confirmed as the primary mode of reproduction for this hermaphroditic nematode in nature. Importantly, we also find evidence for the occurrence of occasional outbreeding. Taken together, these results support the previous notion that C. elegans is a colonizer, whereby selfing may permit rapid dispersal within new habitats even in the absence of potential mates, whereas occasional outcrossing may serve to compensate for the disadvantages of inbreeding. Such information about the natural history of C. elegans should be of great value for an in-depth understanding of the complexity of this organism, including its multifaceted developmental, neurological, or molecular genetic pathways.

The predominantly African origin of all modern human populations is well established, but the route taken out of Africa is still unclear. Two alternative routes, via Egypt and Sinai or across the Bab el Mandeb strait into Arabia, have traditionally been proposed as feasible gateways in light of geographic, paleoclimatic, archaeological, and genetic evidence. Distinguishing among these alternatives has been difficult. We generated 225 whole-genome sequences (225 at 8× depth, of which 8 were increased to 30×; Illumina HiSeq 2000) from six modern Northeast African populations (100 Egyptians and five Ethiopian populations each represented by 25 individuals). West Eurasian components were masked out, and the remaining African haplotypes were compared with a panel of sub-Saharan African and non-African genomes. We showed that masked Northeast African haplotypes overall were more similar to non-African haplotypes and more frequently present outside Africa than were any sets of haplotypes derived from a West African population. Furthermore, the masked Egyptian haplotypes showed these properties more markedly than the masked Ethiopian haplotypes, pointing to Egypt as the more likely gateway in the exodus to the rest of the world. Using five Ethiopian and three Egyptian high-coverage masked genomes and the multiple sequentially Markovian coalescent (MSMC) approach, we estimated the genetic split times of Egyptians and Ethiopians from non-African populations at 55,000 and 65,000 years ago, respectively, whereas that of West Africans was estimated to be 75,000 years ago. Both the haplotype and MSMC analyses thus suggest a predominant northern route out of Africa via Egypt.