A sequencing study comparing ancient and contemporary genomes reveals that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, ancient north Eurasians (related to Upper Palaeolithic Siberians) and early European farmers of mainly Near Eastern origin. By sequencing and comparing the genomes of nine ancient Europeans that bridge the transition to agriculture in Europe between 8,000 and 7,000 years ago, David Reich and colleagues show that most present-day Europeans derive from at least three highly differentiated populations — west European hunter-gatherers, ancient north Eurasians (related to Upper Palaeolithic Siberians) and early European farmers of mainly Near Eastern origin. They further propose that early European farmers had about 44% ancestry from a 'basal Eurasian' population that split before the diversification of other non-African lineages. These results raise interesting new questions, for instance that of where and when the Near Eastern farmers mixed with European hunter-gatherers to produce the early European farmers. We sequenced the genomes of a ∼7,000-year-old farmer from Germany and eight ∼8,000-year-old hunter-gatherers from Luxembourg and Sweden. We analysed these and other ancient genomes1,2,3,4 with 2,345 contemporary humans to show that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians3, who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunter-gatherer related ancestry. We model these populations’ deep relationships and show that early European farmers had ∼44% ancestry from a ‘basal Eurasian’ population that split before the diversification of other non-African lineages.

Genome-wide association studies (GWAS) in coronary artery disease (CAD) had identified 66 loci at 'genome-wide significance' (P < 5 × 10⁻⁸) at the time of this analysis, but a much larger number of putative loci at a false discovery rate (FDR) of 5% (refs. 1,2,3,4). Here we leverage an interim release of UK Biobank (UKBB) data to evaluate the validity of the FDR approach. We tested a CAD phenotype inclusive of angina (SOFT; n_cases = 10,801) as well as a stricter definition without angina (HARD; n_cases = 6,482) and selected cases with the former phenotype to conduct a meta-analysis using the two most recent CAD GWAS^2,3. This approach identified 13 new loci at genome-wide significance, 12 of which were on our previous list of loci meeting the 5% FDR threshold², thus providing strong support that the remaining loci identified by FDR represent genuine signals. The 304 independent variants associated at 5% FDR in this study explain 21.2% of CAD heritability and identify 243 loci that implicate pathways in blood vessel morphogenesis as well as lipid metabolism, nitric oxide signaling and inflammation.

The nonrecombining portion of the human Y chromosome has proven to be a valuable tool for the study of population history. The maintenance of extended haplotypes characteristic of particular geographic regions, despite extensive admixture, allows complex demographic events to be deconstructed. In this study we report the frequencies of 23 Y-chromosome biallelic polymorphism haplotypes in 1,935 men from 49 Eurasian populations, with a particular focus on Central Asia. These haplotypes reveal traces of historical migrations, and provide an insight into the earliest patterns of settlement of anatomically modern humans on the Eurasian continent. Central Asia is revealed to be an important reservoir of genetic diversity, and the source of at least three major waves of migration leading into Europe, the Americas, and India. The genetic results are interpreted in the context of Eurasian linguistic patterns.

North African populations are distinct from sub-Saharan Africans based on cultural, linguistic, and phenotypic attributes; however, the time and the extent of genetic divergence between populations north and south of the Sahara remain poorly understood. Here, we interrogate the multilayered history of North Africa by characterizing the effect of hypothesized migrations from the Near East, Europe, and sub-Saharan Africa on current genetic diversity. We present dense, genome-wide SNP genotyping array data (730,000 sites) from seven North African populations, spanning from Egypt to Morocco, and one Spanish population. We identify a gradient of likely autochthonous Maghrebi ancestry that increases from east to west across northern Africa; this ancestry is likely derived from “back-to-Africa” gene flow more than 12,000 years ago (ya), prior to the Holocene. The indigenous North African ancestry is more frequent in populations with historical Berber ethnicity. In most North African populations we also see substantial shared ancestry with the Near East, and to a lesser extent sub-Saharan Africa and Europe. To estimate the time of migration from sub-Saharan populations into North Africa, we implement a maximum likelihood dating method based on the distribution of migrant tracts. In order to first identify migrant tracts, we assign local ancestry to haplotypes using a novel, principal component-based analysis of three ancestral populations. We estimate that a migration of western African origin into Morocco began about 40 generations ago (approximately 1,200 ya); a migration of individuals with Nilotic ancestry into Egypt occurred about 25 generations ago (approximately 750 ya). Our genomic data reveal an extraordinarily complex history of migrations, involving at least five ancestral populations, into North Africa. Proposed migrations between North Africa and neighboring regions have included Paleolithic gene flow from the Near East, an Arabic migration across the whole of North Africa 1,400 years ago (ya), and trans-Saharan transport of slaves from sub-Saharan Africa. Historical records, archaeology, and mitochondrial and Y-chromosome DNA have been marshaled in support of one theory or another, but there is little consensus regarding the overall genetic background of North African populations or their origin and expansion. We characterize the patterns of genetic variation in North Africa using ∼730,000 single nucleotide polymorphisms from across the genome for seven populations. We observe two distinct, opposite gradients of ancestry: an east-to-west increase in likely autochthonous North African ancestry and an east-to-west decrease in likely Near Eastern Arabic ancestry. The indigenous North African ancestry may have been more common in Berber populations and appears most closely related to populations outside of Africa, but divergence between Maghrebi peoples and Near Eastern/Europeans likely precedes the Holocene (>12,000 ya). We also find significant signatures of sub-Saharan African ancestry that vary substantially among populations. These sub-Saharan ancestries appear to be a recent introduction into North African populations, dating to about 1,200 years ago in southern Morocco and about 750 years ago into Egypt, possibly reflecting the patterns of the trans-Saharan slave trade that occurred during this period.

The nature and underlying mechanisms of an inverse association between adult height and the risk of coronary artery disease (CAD) are unclear. We used a genetic approach to investigate the association between height and CAD, using 180 height-associated genetic variants. We tested the association between a change in genetically determined height of 1 SD (6.5 cm) with the risk of CAD in 65,066 cases and 128,383 controls. Using individual-level genotype data from 18,249 persons, we also examined the risk of CAD associated with the presence of various numbers of height-associated alleles. To identify putative mechanisms, we analyzed whether genetically determined height was associated with known cardiovascular risk factors and performed a pathway analysis of the height-associated genes. We observed a relative increase of 13.5% (95% confidence interval [CI], 5.4 to 22.1; P<0.001) in the risk of CAD per 1-SD decrease in genetically determined height. There was a graded relationship between the presence of an increased number of height-raising variants and a reduced risk of CAD (odds ratio for height quartile 4 versus quartile 1, 0.74; 95% CI, 0.68 to 0.84; P<0.001). Of the 12 risk factors that we studied, we observed significant associations only with levels of low-density lipoprotein cholesterol and triglycerides (accounting for approximately 30% of the association). We identified several overlapping pathways involving genes associated with both development and atherosclerosis. There is a primary association between a genetically determined shorter height and an increased risk of CAD, a link that is partly explained by the association between shorter height and an adverse lipid profile. Shared biologic processes that determine achieved height and the development of atherosclerosis may explain some of the association. (Funded by the British Heart Foundation and others.)