Mait Metspalu

University of Tartu · Institute of Genomics

Background The Italic Iron Age is characterized by the presence of various ethnic groups partially examined from a genomic perspective. To explore the evolution of Iron Age Italic populations and the genetic impact of Romanization, we focus on the Picenes, one of the most fascinating pre-Roman civilizations, who flourished on the Middle Adriatic si...

Substance Use Disorders (SUDs) are a significant public health concern with complex etiologies involving genetic, environmental, and psychological factors. Here we present BioSUD, a biobank that, by integrating genomic data with comprehensive phenotypic assessments, including sociodemographic, psychosocial, and addiction-related variables, was deve...

Italian genetic history was profoundly shaped by Romans. While the Iron Age was comparable to contemporary European regions, the gene pool of Central Italy underwent significant influence from Near Eastern ancestry during the Imperial age. To explain this shift, it has been proposed that during this period people from Eastern Mediterranean regions...

Large biobanks have set a new standard for research and innovation in human genomics and implementation of personalised medicine. The Estonian Biobank was founded a quarter of a century ago, and its biological specimens, clinical, health, omics, and lifestyle data have been included in over 800 publications to date. What makes the biobank unique in...

The demographic history of the Papua New Guinean population is a subject of significant interest due to its early settlement in New Guinea, at least 50 thousand years ago, and its relative isolation compared to other out of Africa populations. This isolation, combined with substantial Denisovan ancestry, contributes to the unique genetic makeup of...

The Roman period saw the empire expand across Europe and the Mediterranean, including much of what is today Great Britain. While there is written evidence of high mobility into and out of Britain for administrators, traders, and the military, the impact of imperialism on local, rural population structure, kinship, and mobility is invisible in the t...

The genetic structure in Europe was mostly shaped by admixture between the Western Hunter-Gatherers, Early European Farmers and Steppe Bronze Age ancestral components. Such structure is regarded as a confounder in GWAS and follow-up studies, and gold-standard methods exist to correct for it. However, it is still poorly understood to which extent th...

Background The COVID-19 pandemic was characterised by rapid waves of disease, carried by the emergence of new and more infectious SARS-CoV-2 virus variants. How the pandemic unfolded in various locations during its first two years has yet to be sufficiently covered. To this end, here we are looking at the circulating SARS-CoV-2 variants, their dive...

The history of human populations has been strongly shaped by admixture events, contributing to the patterns of observed genetic diversity across populations. Given its significance for evolutionary and medical studies, many algorithms focusing on the inference of the genetic composition of admixed populations have been developed. In particular, the...

Highlanders and lowlanders of Papua New Guinea have faced distinct environmental stress, such as hypoxia and environment-specific pathogen exposure, respectively. In this study, we explored the top genomics regions and the candidate driver SNPs for selection in these two populations using newly sequenced whole-genomes of 54 highlanders and 74 lowla...

The Oirats are a group of Mongolian-speaking peoples residing in Russia, China, and Mongolia, who speak Oirat dialects of the Mongolian language. Migrations of nomadic ethnopolitical formations of the Oirats across the Eurasian Steppe during the Late Middle Ages/early Modern times resulted in a wide geographic spread of Oirat ethnic groups from pre...

Background: The Italic Iron Age was characterized by the presence of various ethnic groups partially examined from a genomic perspective. To explore the evolution of Iron Age Italic populations and the genetic impact of Romanization, we focused on the Picenes, one of the most fascinating pre-Roman civilizations, who flourished on the Middle Adriati...

Spatial genetic structure observed in many human populations is in large part attributed to past demographic events and isolation by distance. However, how intensifying migration affects this structure remains understudied. Here we harness a sample of more than 180 thousand individuals to explore the genetic correlates and consequences of contempor...

The genetic structure in Europe was mostly shaped by admixture between the Western Hunter-Gatherer, Anatolian Neolithic and Steppe's Yamnaya ancestral components. Such structure is regarded as a confounder in GWAS and follow-up studies, and gold-standard methods exist to correct for it. However, it is still poorly understood to which extent these a...

The Roman period saw the empire expand across Europe and the Mediterranean, including much of what is today the United Kingdom. While there is written evidence of high mobility into and out of Britain for administrators, traders and the military, the impact of imperialism on local population structure is invisible in the textual record. The extent...

Although dozens of ancient Yersinia pestis genomes and a vast corpus of documentary data are available, the origin and spread of consecutive outbreaks of the Second Plague Pandemic in Europe (14th-18th c.) are still poorly understood. For the majority of ancient genomes, only radiocarbon dates spanning several decades are available, hampering an as...

Background The Sahelian Fulani are the largest nomadic pastoral ethnic group. Their origins are still largely unknown and their Eurasian genetic component is usually explained by recent admixture events with northern African groups. However, it has also been proposed that Fulani may be the descendants of ancient groups settled in the Sahara during...

Highlanders and lowlanders of Papua New Guinea (PNG) have faced distinct environmental conditions. These environmental differences lead to specific stress on PNG highlanders and lowlanders, such as hypoxia and environment-specific pathogen exposure, respectively. We hypothesise that these constraints induced specific selective pressures that shaped...

Human herpes simplex virus 1 (HSV-1), a life-long infection spread by oral contact, infects a majority of adults globally. Phylogeographic clustering of sampled diversity into European, pan-Eurasian, and African groups has suggested the virus codiverged with human migrations out of Africa, although a much younger origin has also been proposed. We p...

Mutations in the GJB2 gene are known to be a major cause of autosomal recessive deafness 1A (OMIM 220290). The most common pathogenic variants of the GJB2 gene have a high ethno-geographic specificity in their distribution, being attributed to a founder effect related to the Neolithic migration routes of Homo sapiens. The c.-23 + 1G > A splice site...

Our exploration of the genetic constitution of Nuku Hiva (n = 51), Hiva Oa (n = 28) and Tahuata (n = 8) of the Marquesas Archipelago based on the analyses of genome-wide autosomal markers as well as high-resolution genotyping of paternal and maternal lineages provides us with information on the origins and settlement of these islands at the fringe...

Island Southeast Asia (ISEA) and Oceania host one of the world's richest assemblages of human phenotypic, linguistic, and cultural diversity. Despite this, the region's male genetic lineages are globally among the last to remain unresolved. We compiled ∼9.7 Mb of Y chromosome (chrY) sequence from a diverse sample of over 380 men from this region, i...

Background The human pathogen Haemophilus influenzae was the main cause of bacterial meningitis in children and a major cause of worldwide infant mortality before the introduction of a vaccine in the 1980s. Although the occurrence of serotype b (Hib), the most virulent type of H. influenzae , has since decreased, reports of infections with other se...

The contemporary European genetic makeup formed in the last 8,000 years when local Western Hunter-Gatherers (WHGs) mixed with incoming Anatolian Neolithic farmers and Pontic Steppe pastoralists.1, 2, 3 This encounter combined genetic variants with distinct evolutionary histories and, together with new environmental challenges faced by the post-Neol...

Objectives The objective of this study was to assess the population prevalence of SARS-CoV-2 and changes in the prevalence in the adult general population in Estonia during the 1st year of COVID-19 epidemic. Study design A population-based nationwide sequential/consecutive cross-sectional study. Methods Using standardised methodology (population-...

Human herpes simplex virus 1 (HSV-1), a life-long infection spread by oral contact, today infects a majority of adults globally, yet no ancient HSV-1 genomes have yet been published. Phylogeographic clustering of sampled diversity into European, pan-Eurasian, and African groups(Pfaff et al. 2016; Szpara, Tafuri, et al. 2014) has suggested that the...

The geographical location and shape of Apulia, a narrow land stretching out in the sea at the South of Italy, made this region a Mediterranean crossroads connecting Western Europe and the Balkans. Such movements culminated at the beginning of the Iron Age with the Iapygian civilisation which consisted of three cultures: Peucetians, Messapians and D...

Lack of diversity in human genomics limits our understanding of the genetic underpinnings of complex traits, hinders precision medicine, and contributes to health disparities. To map genetic effects on gene regulation in the underrepresented Indonesian population, we have integrated genotype, gene expression, and CpG methylation data from 115 parti...

A general imbalance in the proportion of disembarked males and females in the Americas has been documented during the Trans-Atlantic Slave Trade and the Colonial Era and, although less prominent, more recently. This imbalance may have left a signature on the genomes of modern-day populations characterised by high levels of admixture. The analysis o...

The settlement of Sahul, the lost continent of Oceania, remains one of the most ancient and debated human migrations. Modern New Guineans inherited a unique genetic diversity tracing back 50,000 years, and yet there is currently no model reconstructing their past population dynamics. We generated 58 new whole genome sequences from Papua New Guinea,...

The contemporary European genetic makeup formed in the last 8000 years as the combination of three main genetic components: the local Western Hunter-Gatherers, the incoming Neolithic Farmers from Anatolia and the Bronze Age component from the Pontic Steppes. When meeting into the post-Neolithic European environment, the genetic variants accumulated...

The Finnish population is a unique example of a genetic isolate affected by a recent founder event. Previous studies have suggested that the ancestors of Finnic-speaking Finns and Estonians reached the circum-Baltic region by the 1st millennium BC. However, high linguistic similarity points to a more recent split of their languages. To study geneti...

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genodermatosis caused by mutations in the gene coding for type VII collagen (COL7A1). More than 800 different pathogenic mutations in COL7A1 have been described to date; however, the ancestral origins of many of these mutations have not been precisely identified. In this study, 32 RDEB pat...

The geographical location and shape of Apulia, a narrow land stretching out in the sea at the South of Italy, made this region a Mediterranean crossroads connecting Western Europe and the Balkans. Such movements culminated at the beginning of the Iron Age with the Iapygian civilization which consisted of three cultures: Peucetians, Messapians and D...

American populations are one of the most interesting examples of recently admixed groups, where ancestral components from three major continental human groups (Africans, Eurasians and Native Americans) have admixed within the last 15 generations. Recently, several genetic surveys focusing on thousands of individuals shed light on the geography, chr...

Across Europe, the genetics of the Chalcolithic/Bronze Age transition is increasingly characterized in terms of an influx of Steppe-related ancestry. The effect of this major shift on the genetic structure of populations in the Italian Peninsula remains underexplored. Here, genome-wide shotgun data for 22 individuals from commingled cave and single...

Human Y chromosome haplogroup J1-M267 is a common male lineage in West Asia. One high-frequency region—encompassing the Arabian Peninsula, southern Mesopotamia, and the southern Levant—resides ~ 2000 km away from the other one found in the Caucasus. The region between them, although has a lower frequency, nevertheless demonstrates high genetic dive...

This article reports on the genetic characteristics of the Ami and Yami, two aboriginal populations of Taiwan. Y-SNP and mtDNA markers as well as autosomal SNPs were utilized to investigate the phylogenetic relationships to groups from MSEA (mainland Southeast Asia), ISEA (island Southeast Asia), and Oceania. Both the Ami and Yami have limited gene...

Recent studies have showed the diverse genetic architecture of the highly consanguineous populations inhabiting the Arabian Peninsula. Consanguinity coupled with heterogeneity is complex and makes it difficult to understand the bases of population-specific genetic diseases in the region. Therefore, comprehensive genetic characterization of the popu...

The recently enriched genomic history of Indigenous groups in the Americas is still meager concerning continental Central America. Here, we report ten pre-Hispanic (plus two early colonial) genomes and 84 genome-wide profiles from seven groups presently living in Panama. Our analyses reveal that pre-Hispanic demographic events contributed to the ex...

The transition from Stone to Bronze Age in Central and Western Europe was a period of major population movements originating from the Ponto-Caspian Steppe. Here, we report new genome-wide sequence data from 30 individuals north of this area, from the understudied western part of present-day Russia, including 3 Stone Age hunter-gatherers (10,800 to...

American populations are one of the most interesting examples of recently admixed groups, where ancestral components from three major continental human groups (Africans, Eurasians and Native Americans) have admixed within the last 15 generations. Recently, several genetic surveys focusing on thousands of individuals shed light on the geography, chr...

Recent studies have showed the diverse genetic architecture of the highly consanguineous populations inhabiting the Arabian Peninsula. Consanguinity coupled with heterogeneity is complex and makes it difficult to understand the bases of population-specific genetic diseases in the region. Therefore, comprehensive genetic characterization of the popu...

The recently enriched genomic history of Indigenous groups in the Americas is still meagre concerning continental Central America. Here, we report ten pre-Hispanic (plus two early colonial) genomes and 84 genome-wide profiles from seven groups presently living in Panama. Our analyses reveal that pre-Hispanic demographic changes and isolation events...

The phylogenetic analysis of Y chromosomal haplogroup O2a-M95 was crucial to determine the nested structure of South Asian branches within the larger tree, predominantly present in East and Southeast Asia. However, it had previously been unclear that how many founders brought the haplogroup O2a-M95 to South Asia. On the basis of the updated Y chrom...

The phylogenetic analysis of Y chromosomal haplogroup O2a-M95 was crucial to determine the nested structure of South Asian branches within the larger tree, predominantly present in East and Southeast Asia. However, it had previously been unclear that how many founders brought the haplogroup O2a-M95 to South Asia. On the basis of the updated Y chrom...

Lack of diversity in human genomics limits our understanding of the genetic underpinnings of complex traits, hinders precision medicine, and contributes to health disparities. To map genetic effects on gene regulation in the underrepresented Indonesian population, we have integrated genotype, gene expression, and CpG methylation data from 115 parti...

Several recent studies detected fine-scale genetic structure in human populations. Hence, groups conventionally treated as single populations harbour significant variation in terms of allele frequencies and patterns of haplotype sharing. It has been shown that these findings should be considered when performing studies of genetic associations and n...

Transition from the Stone to the Bronze Age in Central and Western Europe was a period of major population movements originating from the Ponto-Caspian Steppe. Here, we report new genome-wide sequence data from 28 individuals from the territory north of this source area - from the under-studied Western part of present-day Russia, including Stone Ag...

New Guineans represent one of the oldest locally continuous populations outside Africa, harboring among the greatest linguistic and genetic diversity on the planet. Archeological and genetic evidence suggest that their ancestors reached Sahul (present day New Guinea and Australia) by at least 55,000 years ago (kya). However, little is known about t...

Polygenic Scores (PSs) describe the genetic component of an individual's quantitative phenotype or their susceptibility to diseases with a genetic basis. Currently, PSs rely on population-dependent contributions of many associated alleles, with limited applicability to understudied populations and recently admixed individuals. Here we introduce a c...

Two ancient Egyptian child mummies at the University of Tartu Art Museum (Estonia) were, according to museum records, brought to Estonia by the young Baltic-German scholar Otto Friedrich von Richter, who had travelled in Egypt during the early 19th century. Although some studies of the mummies were conducted, a thorough investigation has never been...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The phylogenetic analysis of Y chromosomal haplogroup O2a-M95 was crucial to determine the nested structure of South Asian branches within the larger tree, predominantly present in East and Southeast Asia. However, it had previously been unclear how many founders brought the haplogroup O2a-M95 to South Asia. On the basis of the updated Y chromosoma...

The human genetic diversity of the Americas has been affected by several events of gene flow that have continued since the colonial era and the Atlantic slave trade. Moreover, multiple waves of migration followed by local admixture occurred in the last two centuries, the impact of which has been largely unexplored. Here, we compiled a genome-wide d...

Despite being the fourth largest island in the Mediterranean basin, the genetic variation of Corsica has not been explored as exhaustively as Sardinia, which is situated only 11 km South. However, it is likely that the populations of the two islands shared, at least in part, similar demographic histories. Moreover, the relative small size of the Co...

Despite being the fourth largest island in the Mediterranean basin, the genetic variation of Corsica has not been explored as exhaustively as Sardinia, which is situated only 11 km South. However, it is likely that the populations of the two islands shared, at least in part, similar demographic histories. Moreover, the relative small size of the Co...

The Early Iron Age nomadic Scythians have been described as a confederation of tribes of different origins, based on ancient DNA evidence [1-3]. It is still unclear how much of the Scythian dominance in the Eurasian Steppe was due to movements of people and how much reflected cultural diffusion and elite dominance. We present new whole-genome seque...

The human genetic diversity of the Americas has been shaped by several events of gene flow that have continued since the Colonial Era and the Atlantic slave trade. Moreover, multiple waves of migration followed by local admixture occurred in the last two centuries, the impact of which has been largely unexplored. Here we compiled a genome-wide data...

In this study, we compare the genetic ancestry of individuals from two as yet genetically unstudied cultural traditions in Estonia in the context of available modern and ancient datasets: 15 from the Late Bronze Age stone-cist graves (1200–400 BC) (EstBA) and 6 from the Pre-Roman Iron Age tarand cemeteries (800/500 BC–50 AD) (EstIA). We also includ...

The indigenous populations of inner Eurasia—a huge geographic region covering the central Eurasian steppe and the northern Eurasian taiga and tundra—harbour tremendous diversity in their genes, cultures and languages. In this study, we report novel genome-wide data for 763 individuals from Armenia, Georgia, Kazakhstan, Moldova, Mongolia, Russia, Ta...

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Haplotype-based methods are a cost-effective alternative to characterize unobserved rare variants and map disease-associated alleles. Moreover, they can be used to reconstruct recent population history, which shaped distribution of rare variants and thus can be used to guide gene mapping studies. In this study, we analysed Illumina 650 k genotyped...