Ticagrelor vs Prasugrel for Acute Coronary Syndrome in Routine Care.

Importance: In patients with acute coronary syndrome (ACS) undergoing invasive treatment, ticagrelor and prasugrel are guideline-recommended P2Y12 receptor inhibitors. The ISAR-REACT5 randomized clinical trial demonstrated superiority for prasugrel, although concerns were raised about the generalizability of some underpowered subgroup analyses.

Objectives: To emulate a randomized clinical trial evaluating the safety and effectiveness of ticagrelor vs prasugrel under the conditions of routine care in individuals with ACS planned to undergo an invasive treatment strategy.

Genomic perspectives on human dispersals during the Holocene.

Nearly 20 y ago, Jared Diamond and Peter Bellwood reviewed the evidence for the associated spread of farming and large language families by the demographic expansions of farmers. Since then, advances in obtaining and analyzing genomic data from modern and ancient populations have transformed our knowledge of human dispersals during the Holocene. Here, we provide an overview of Holocene dispersals in the light of genomic evidence and conclude that they have a complex history.

Ancient genomes from the last three millennia support multiple human dispersals into Wallacea.

Previous research indicates that human genetic diversity in Wallacea-islands in present-day Eastern Indonesia and Timor-Leste that were never part of the Sunda or Sahul continental shelves-has been shaped by complex interactions between migrating Austronesian farmers and indigenous hunter-gatherer communities. Yet, inferences based on present-day groups proved insufficient to disentangle this region's demographic movements and admixture timings. Here, we investigate the spatio-temporal patterns of variation in Wallacea based on genome-wide data from 16 ancient individuals (2600-250 years BP) from the North Moluccas, Sulawesi and East Nusa Tenggara.

Ancient DNA from Guam and the peopling of the Pacific.

Humans reached the Mariana Islands in the western Pacific by ∼3,500 y ago, contemporaneous with or even earlier than the initial peopling of Polynesia. They crossed more than 2,000 km of open ocean to get there, whereas voyages of similar length did not occur anywhere else until more than 2,000 y later. Yet, the settlement of Polynesia has received far more attention than the settlement of the Marianas.

The Current Genomic Landscape of Western South America: Andes, Amazonia, and Pacific Coast.

Studies of Native South American genetic diversity have helped to shed light on the peopling and differentiation of the continent, but available data are sparse for the major ecogeographic domains. These include the Pacific Coast, a potential early migration route; the Andes, home to the most expansive complex societies and to one of the most widely spoken indigenous language families of the continent (Quechua); and Amazonia, with its understudied population structure and rich cultural diversity. Here, we explore the genetic structure of 176 individuals from these three domains, genotyped with the Affymetrix Human Origins array.

The Gateway from Near into Remote Oceania: New Insights from Genome-Wide Data.

A widely accepted two-wave scenario of human settlement of Oceania involves the first out-of-Africa migration circa 50,000 years ago (ya), and the more recent Austronesian expansion, which reached the Bismarck Archipelago by 3,450 ya. Whereas earlier genetic studies provided evidence for extensive sex-biased admixture between the incoming and the indigenous populations, some archaeological, linguistic, and genetic evidence indicates a more complicated picture of settlement. To study regional variation in Oceania in more detail, we have compiled a genome-wide data set of 823 individuals from 72 populations (including 50 populations from Oceania) and over 620,000 autosomal single nucleotide polymorphisms (SNPs).

A genomic history of Aboriginal Australia.

The population history of Aboriginal Australians remains largely uncharacterized. Here we generate high-coverage genomes for 83 Aboriginal Australians (speakers of Pama-Nyungan languages) and 25 Papuans from the New Guinea Highlands. We find that Papuan and Aboriginal Australian ancestors diversified 25-40 thousand years ago (kya), suggesting pre-Holocene population structure in the ancient continent of Sahul (Australia, New Guinea and Tasmania).

The Complex Admixture History and Recent Southern Origins of Siberian Populations.

Although Siberia was inhabited by modern humans at an early stage, there is still debate over whether it remained habitable during the extreme cold of the Last Glacial Maximum or whether it was subsequently repopulated by peoples with recent shared ancestry. Previous studies of the genetic history of Siberian populations were hampered by the extensive admixture that appears to have taken place among these populations, because commonly used methods assume a tree-like population history and at most single admixture events. Here we analyze geogenetic maps and use other approaches to distinguish the effects of shared ancestry from prehistoric migrations and contact, and develop a new method based on the covariance of ancestry components, to investigate the potentially complex admixture history.

Genome-wide insights into the genetic history of human populations.

Although mtDNA and the non-recombining Y chromosome (NRY) studies continue to provide valuable insights into the genetic history of human populations, recent technical, methodological and computational advances and the increasing availability of large-scale, genome-wide data from contemporary human populations around the world promise to reveal new aspects, resolve finer points, and provide a more detailed look at our past demographic history. Genome-wide data are particularly useful for inferring migrations, admixture, and fine structure, as well as for estimating population divergence and admixture times and fluctuations in effective population sizes. In this review, we highlight some of the stories that have emerged from the analyses of genome-wide SNP genotyping data concerning the human history of Southern Africa, India, Oceania, Island South East Asia, Europe and the Americas and comment on possible future study directions.

Genome-wide data substantiate Holocene gene flow from India to Australia.

The Australian continent holds some of the earliest archaeological evidence for the expansion of modern humans out of Africa, with initial occupation at least 40,000 y ago. It is commonly assumed that Australia remained largely isolated following initial colonization, but the genetic history of Australians has not been explored in detail to address this issue. Here, we analyze large-scale genotyping data from aboriginal Australians, New Guineans, island Southeast Asians and Indians.

Genetic dating indicates that the Asian-Papuan admixture through Eastern Indonesia corresponds to the Austronesian expansion.

Although the Austronesian expansion had a major impact on the languages of Island Southeast Asia, controversy still exists over the genetic impact of this expansion. The coexistence of both Asian and Papuan genetic ancestry in Eastern Indonesia provides a unique opportunity to address this issue. Here, we estimate recombination breakpoints in admixed genomes based on genome-wide SNP data and date the genetic admixture between populations of Asian vs.

Denisova admixture and the first modern human dispersals into Southeast Asia and Oceania.

It has recently been shown that ancestors of New Guineans and Bougainville Islanders have inherited a proportion of their ancestry from Denisovans, an archaic hominin group from Siberia. However, only a sparse sampling of populations from Southeast Asia and Oceania were analyzed. Here, we quantify Denisova admixture in 33 additional populations from Asia and Oceania.

Dating the age of admixture via wavelet transform analysis of genome-wide data.

We describe a PCA-based genome scan approach to analyze genome-wide admixture structure, and introduce wavelet transform analysis as a method for estimating the time of admixture. We test the wavelet transform method with simulations and apply it to genome-wide SNP data from eight admixed human populations. The wavelet transform method offers better resolution than existing methods for dating admixture, and can be applied to either SNP or sequence data from humans or other species.

Genetic variation and recent positive selection in worldwide human populations: evidence from nearly 1 million SNPs.

Background: Genome-wide scans of hundreds of thousands of single-nucleotide polymorphisms (SNPs) have resulted in the identification of new susceptibility variants to common diseases and are providing new insights into the genetic structure and relationships of human populations. Moreover, genome-wide data can be used to search for signals of recent positive selection, thereby providing new insights into the genetic adaptations that occurred as modern humans spread out of Africa and around the world.

Methodology: We genotyped approximately 500,000 SNPs in 255 individuals (5 individuals from each of 51 worldwide populations) from the Human Genome Diversity Panel (HGDP-CEPH).

Positive selection in East Asians for an EDAR allele that enhances NF-kappaB activation.

Genome-wide scans for positive selection in humans provide a promising approach to establish links between genetic variants and adaptive phenotypes. From this approach, lists of hundreds of candidate genomic regions for positive selection have been assembled. These candidate regions are expected to contain variants that contribute to adaptive phenotypes, but few of these regions have been associated with phenotypic effects.