Modern Human Populations Research Articles

Advancements and prospects in reconstructing the genetic genealogies of ancient and modern human populations using ancestral recombination graphs.

With the release of large-scale genomic resources from ancient and modern populations, advancements in computational biology tools, and the enhancement of data mining capabilities, the field of genomics is undergoing a revolutionary transformation. These advancements and changes have not only significantly deepened our understanding of the complex evolutionary processes of human origins, migration, and admixture but have also unveiled the impact of these processes on human health and disease. They have accelerated research into the genetic basis of human health and disease and provided new avenues for uncovering the evolutionary trajectories recorded in the human genome related to population history and disease genetics. The ancestral recombination graph (ARG) reconstructs the evolutionary relationships between genomic segments by analyzing recombination events and coalescence patterns across different regions of the genome. An ARG provides a record of all coalescence and recombination events since the divergence of the sequences under study and specifies a complete genealogy at each genomic position, which is the ideal data structure for genomic analysis. Here, we review the theoretical foundations and research advancements of the ARG, and explore its translational applications and future prospects across various disciplines, including forensic genomics, population genetics, evolutionary medicine, and medical genomics. Our goal is to promote the application of this technique in genomic research, thereby deepening our understanding of the human genome.

Local Ancestry Inference Based on Population-Specific Single-Nucleotide Polymorphisms-A Study of Admixed Populations in the 1000 Genomes Project.

Human populations have interacted throughout history, and a considerable portion of modern human populations show evidence of admixture. Local ancestry inference (LAI) is focused on detecting the genetic ancestry of chromosomal segments in admixed individuals and has wide applications. In this work, we proposed a new LAI method based on population-specific single-nucleotide polymorphisms (SNPs) and applied it in the analysis of admixed populations in the 1000 Genomes Project (1KGP). Based on population-specific SNPs in a sliding window, we computed local ancestry information vectors, which are moment estimators of local ancestral proportions, for two haplotypes of an admixed individual and inferred the local ancestral origins. Then we used African (AFR), East Asian (EAS), European (EUR) and South Asian (SAS) populations from the 1KGP and indigenous American (AMR) populations from the Human Genome Diversity Project (HGDP) as reference populations and conducted the proposed LAI analysis on African American populations and American populations in the 1KGP. The results were compared with those obtained by RFMix, G-Nomix and FLARE. We demonstrated that the existence of alleles in a chromosomal region that are specific to a particular reference population and the absence of alleles specific to the other reference populations provide reasonable evidence for determining the ancestral origin of the region. Contemporary AFR, AMR and EUR populations approximate ancestral populations of the admixed populations well, and the results from RFMix, G-Nomix and FLARE largely agree with those from the Ancestral Spectrum Analyzer (ASA), in which the proposed method was implemented. When admixtures are ancient and contemporary reference populations do not satisfactorily approximate ancestral populations, the performances of RFMix, G-Nomix and FLARE deteriorate with increased error rates and fragmented chromosomal segments. In contrast, our method provides fair results.

Global diversity, recurrent evolution, and recent selection on amylase structural haplotypes in humans.

The adoption of agriculture, first documented ~12,000 years ago in the Fertile Crescent, triggered a rapid shift toward starch-rich diets in human populations. Amylase genes facilitate starch digestion and increased salivary amylase copy number has been observed in some modern human populations with high starch intake, though evidence of recent selection is lacking. Here, using 52 long-read diploid assemblies and short read data from ~5,600 contemporary and ancient humans, we resolve the diversity, evolutionary history, and selective impact of structural variation at the amylase locus. We find that amylase genes have higher copy numbers in populations with agricultural subsistence compared to fishing, hunting, and pastoral groups. We identify 28 distinct amylase structural architectures and demonstrate that nearly identical structures have arisen recurrently on different haplotype backgrounds throughout recent human history. AMY1 and AMY2A genes each exhibit multiple duplications/deletions with mutation rates >10,000-fold the SNP mutation rate, whereas AMY2B gene duplications share a single origin. Using a pangenome graph-based approach to infer structural haplotypes across thousands of humans, we identify extensively duplicated haplotypes present at higher frequencies in modern day populations with traditionally agricultural diets. Leveraging 533 ancient human genomes we find that duplication-containing haplotypes (i.e. haplotypes with more amylase gene copies than the ancestral haplotype) have increased in frequency more than seven-fold over the last 12,000 years providing evidence for recent selection in West Eurasians. Together, our study highlights the potential impacts of the agricultural revolution on human genomes and the importance of long-read sequencing in identifying signatures of selection at structurally complex loci.

Using horse teeth to shape stone tools: an experimental approach to characterise use-wear traces

Horse tooth retouchers have been identified in several Middle and Upper Palaeolithic sites. They have been typically characterised as ‘soft’ hammers and/or grouped into the category of ‘bone retouchers’ at a technical level. Bone and teeth have different chemical compositions; teeth are denser and heavier than bone, and consequently, their technological features should not be considered homologous. In this work, we experimentally tested the effectiveness of horse teeth as retouchers. To perform this study, we used 41 modern horse teeth to shape flakes of various raw materials by applying different techniques. The resulting use-wear traces were analysed using high-resolution methods and then characterised. The results allowed us to identify the effectiveness of hypsodont teeth in knapping a wide range of tools and to evaluate the influence of 1) the raw materials, 2) the retouching techniques and 3) the gestures of the different knappers on the morphology of the use-wear marks. This work sheds light on the purpose of using teeth as tools by both Neanderthal and early modern human populations as well as understanding how these human species used them. The study leads us to consider tooth retouchers as important elements of the chaîne opératoire in lithic manufacture. Our goal is to highlight the importance of these types of experimental studies to create analogies and infer past processes.

PNPLA3 fatty liver allele was fixed in Neanderthals and segregates neutrally in humans

ObjectiveFat deposition is modulated by environmental factors and genetic predisposition. Genome-wide association studies identified PNPLA3 p.I148M (rs738409) as a common variant that increases risk of developing liver steatosis. When and...

Competing forces: Subsistence strategies and human-carnivore interactions during the middle to Upper Palaeolithic transition in Northern Iberia

The comparative assessment of dietary choices as part of landscape use strategies deployed by Neanderthal and Anatomically Modern Human populations in Eurasia constitutes a fundamental avenue of Palaeolithic research. The increasing number of taphonomic assessments enables a better understanding of what remains were brought to sites by human hunters versus mammalian carnivores or raptors. A zooarchaeological approach can further elucidate the spatio-temporal dynamics of interaction between carnivores and human populations in terms of landscape use and prey choice during this transitional period. To achieve this objective, we conducted an examination of zooarchaeological and taphonomic data, carnivore indices, and other relevant variables across 36 Middle and Early Upper Palaeolithic sites in northern Iberia. These sites encompass 126 archaeological layers dating from 50,000 to 30,000 years ago. Our comprehensive bibliographic meta-analysis reveals that human occupations by both groups at sites across the region were punctuated by episodes influenced by carnivores. This observation implies that human occupations in northern Iberia during Marine Isotope Stage 3 were generally characterised by instability and limited to short periods, often seasonal in nature. From a zooarchaeological perspective, the combined assessment of taxonomic data, species richness and assemblage diversity highlights that the range and proportion of species acquired by these different human groups are similar, although Anatomically Modern Humans engaged in a sustained trend towards increasing dietary diversification even at sites with assemblages heavily dominated by one taxon.

NextDenovo: an efficient error correction and accurate assembly tool for noisy long reads

Long-read sequencing data, particularly those derived from the Oxford Nanopore sequencing platform, tend to exhibit high error rates. Here, we present NextDenovo, an efficient error correction and assembly tool for noisy long reads, which achieves a high level of accuracy in genome assembly. We apply NextDenovo to assemble 35 diverse human genomes from around the world using Nanopore long-read data. These genomes allow us to identify the landscape of segmental duplication and gene copy number variation in modern human populations. The use of NextDenovo should pave the way for population-scale long-read assembly using Nanopore long-read data.

Improving of Amaranth (Amaranthus Spp.) and Quinoa (Chenopodium quinoa) by Genetic Resources

The modern human population is more mindful of their diet and choose foods carefully in order to maintain a healthy lifestyle and prevent illness. Thus, instead of sticking to their long-standing diets of ordinary cereals and basic foods, individuals are starting to choose more intelligent and nutrient-dense dietary choices. Because they are gluten-free, have no added sugar, and are somewhat higher in nutrients than typical cereals, pseudocereals—particularly quinoa and amaranth—are significant substitutes. Both Amaranthaceae crops are hardy, low-input plants that can withstand salt, stress, and drought. Therefore, these crops might be advantageous to emerging nations with limited agricultural resources and subsistence agriculture. But these are neglected orphan crops, and for a very long time, there has been no attempt to enhance them by lowering their saponin content. These crops also have a great degree of variety, but their genetic development towards high-yielding genotypes is sluggish. This is because traditional cereals are facing problems, and crop diversification is the preferred solution to address climate change. The most recent technological advancements that can speed up breeding to increase agricultural output and quality are far behind and move more slowly than the world's primary crops that are already well-established.

Comparative kinetics of humans and non-human primates during vertical climbing.

Climbing represents a critical behavior in the context of primate evolution. However, anatomically modern human populations are considered ill-suited for climbing. This adaptation can be attributed to the evolution of striding bipedalism, redirecting anatomical traits away from efficient climbing. Although prior studies have speculated on the kinetic consequences of this anatomical reorganization, there is a lack of data on the force profiles of human climbers. This study utilized high-speed videography and force plate analysis to assess single limb forces during climbing from 44 human participants of varying climbing experience and compared these data with climbing data from eight species of non-human primates (anthropoids and strepsirrhines). Contrary to expectations, experience level had no significant effect on the magnitude of single limb forces in humans. Experienced climbers did, however, demonstrate a predictable relationship between center of mass position and peak normal forces, suggesting a better ability to modulate forces during climbing. Humans exhibited significantly higher peak propulsive forces in the hindlimb compared with the forelimb and greater hindlimb dominance overall compared with non-human primates. All species sampled demonstrated exclusively tensile forelimbs and predominantly compressive hindlimbs. Strepsirrhines exhibited a pull-push transition in normal forces, while anthropoid primates, including humans, did not. Climbing force profiles are remarkably stereotyped across humans, reflecting the universal mechanical demands of this form of locomotion. Extreme functional differentiation between forelimbs and hindlimbs in humans may help to explain the evolution of bipedalism in ancestrally climbing hominoids.

Spatial ecological gradients and non-equilibrium niche construction dynamics in the Levantine Middle-Upper Palaeolithic transition

This article revisits the Middle-Upper Palaeolithic (MP-UP) transition in the Levant (ca. 50–40 kiloanni calibrated before present, hereafter ka), explored here as a key case of spatially and temporally multiscalar niche construction and biocultural adaptation in recent human evolution. New chronometric and palaeogenomic data provide an opportunity to reconsider what actually changed in the MP-UP transition, not only in terms of Neanderthal-anatomically modern human (AMH) population turnover and biological adaptation, but also culturally transmitted technologies and cultural institutions that mediated interrelated changes in mobility and social-network connectivity. High-resolution satellite data on environmental variability, simulation studies of hunter-gatherer demographic fluctuations, and cross-cultural data on hunter-gatherer population density and social organization are evaluated to model baseline constraints and possibilities for long-term biocultural adaptation and niche construction in the region, across the Middle and Late Pleistocene more broadly (ca. 780–12 ka). This exploration adds theoretical support to a view of the MP-UP transition as evolutionary, rather than revolutionary, offering new avenues of inquiry about how shorter-term, local behavioural responses were affected by and—in turn—had ripple effects on geographically more widespread, longer-term trends involving intergenerational demographic dynamics, centennial or millennial-scale population turnovers, and major long-term technological shifts.

Balkan Neanderthals: The Late Pleistocene palaeoecological sequence of Pešturina Cave (Niš, Serbia)

The Central Balkans are a key biogeographical region in Southern Europe, influenced by a central European-Mediterranean climate, which acted as a refugium for flora and fauna, and favored the dispersion of Neanderthals and migration of modern human populations during Late Glacial Period. This study presents pollen analyses of sediment and hyaena coprolites from Pešturina Cave in Serbia to reconstruct the vegetation landscapes faced by Balkan Neanderthals and early Anatomically Modern Humans between MIS 5e-3. Between MIS 5e-5c (archaeological layers 4c and 4b) and MIS 5b-5a (layer 4a), semi-forested environments prevailed, characterized by Pinus, deciduous Quercus, Tilia and other angiosperm woody taxa, accompanied by heliophytes such as Artemisia and Poaceae. During MIS 4-3 (layers 3-2), the vegetation was dominated by Artemisia-Poaceae steppes with Quercus patches, conifers and legumes. Overall across the sequence, pollen assemblages are highly diverse and include a number of deciduous trees and sclerophylls. In addition, the occurrence of several herbaceous taxa reinforces the view that the Balkans were outstanding for endemicity. Neanderthals and early Upper Palaeolithic hominins lived in a highly diverse refugium, offering multiple opportunities for survival during the warm interstadials and, more critically, the cold stadials of the Pleistocene.

Hominin population bottleneck coincided with migration from Africa during the Early Pleistocene ice age transition

Two recently published analyses make cases for severe bottlenecking of human populations occurring in the late Early Pleistocene, one case at about 0.9 Mya based on a genomic analysis of modern human populations and the low number of hominin sites of this age in Africa and the other at about 1.1 Mya based on an age inventory of sites of hominin presence in Eurasia. Both models point to climate change as the bottleneck trigger, albeit manifested at very different times, and have implications for human migrations as a mechanism to elude extinction at bottlenecking. Here, we assess the climatic and chronologic components of these models and suggest that the several hundred-thousand-year difference is largely an artifact of biases in the chronostratigraphic record of Eurasian hominin sites. We suggest that the best available data are consistent with the Galerian hypothesis expanded from Europe to Eurasia as a major migration pulse of fauna including hominins in the late Early Pleistocene as a consequence of the opening of land routes from Africa facilitated by a large sea level drop associated with the first major ice age of the Pleistocene and concurrent with widespread aridity across Africa that occurred during marine isotope stage 22 at ~0.9 Mya. This timing agrees with the independently dated bottleneck from genomic analysis of modern human populations and allows speculations about the relative roles of climate forcing on the survival of hominins.

Quantifying hominin morphological diversity at the end of the middle Pleistocene: Implications for the origin of Homo sapiens.

The Middle Pleistocene (MP) saw the emergence of new species of hominins: Homo sapiens in Africa, H. neanderthalensis, and possibly Denisovans in Eurasia, whose most recent common ancestor is thought to have lived in Africa around 600 ka ago. However, hominin remains from this period present a wide range of morphological variation making it difficult to securely determine their taxonomic attribution and their phylogenetic position within the Homo genus. This study proposes to reconsider the phenetic relationships between MP hominin fossils in order to clarify evolutionary trends and contacts between the populations they represent. We used a Geometric Morphometrics approach to quantify the morphological variation of the calvarium of controversial MP specimens from Africa and Eurasia by using a comparative sample that can be divided into 5 groups: H. ergaster, H. erectus, H. neanderthalensis, and H. sapiens, as well as individuals from current modern human populations. We performed a Generalized Procrustes Analysis, a Principal Component Analysis, and Multinomial Principal Component Logistic Regressions to determine the phenetic affinities of the controversial Middle Pleistocene specimens with the other groups. MP African and Eurasian specimens represent several populations, some of which show strong affinities with H. neanderthalensis in Europe or H. sapiens in Africa, others presenting multiple affinities. These MP populations might have contributed to the emergence of these two species in different proportions. This study proposes a new framework for the human evolutionary history during the MP.

Atherosclerosis as the Damocles' sword of human evolution: insights from nonhuman ape-like primates, ancient human remains, and isolated modern human populations.

Atherosclerosis is the leading cause of death worldwide, and the predominant risk factors are advanced age and high-circulating low-density lipoprotein cholesterol (LDL-C). However, the findings of atherosclerosis in relatively young mummified remains and a lack of atherosclerosis in chimpanzees despite high LDL-C call into question the role of traditional cardiovascular risk factors. The inflammatory theory of atherosclerosis may explain the discrepancies between traditional risk factors and observed phenomena in current literature. Following the divergence from chimpanzees several millennia ago, loss of function mutations in immune regulatory genes and changes in gene expression have resulted in an overactive human immune system. The ubiquity of atherosclerosis in the modern era may reflect a selective pressure that enhanced the innate immune response at the cost of atherogenesis and other chronic disease states. Evidence provided from the fields of genetics, evolutionary biology, and paleoanthropology demonstrates a sort of circular dependency between inflammation, immune system functioning, and evolution at both a species and cellular level. More recently, the role of proinflammatory stimuli, somatic mutations, and the gene-environment effect appear to be underappreciated elements in the development and progression of atherosclerosis. Neurobiological stress, metabolic syndrome, and traditional cardiovascular risk factors may instead function as intermediary links between inflammation and atherosclerosis. Therefore, considering evolution as a mechanistic process and atherosclerosis as part of the inertia of evolution, greater insight into future preventative and therapeutic interventions for atherosclerosis can be gained by examining the past.

Hemispheric asymmetries in cortical grey matter of gyri and sulci in modern human populations from South America.

Structural asymmetries of brain regions associated with lateralised functions have been extensively studied. However, there are fewer morphometric analyses of asymmetries of the gyri and sulci of the entire cortex. The current study assessed cortical asymmetries in a sample of healthy adults (N = 175) from an admixed population from South America. Grey matter volume and surface area of 66 gyri and sulci were quantified on T1 magnetic resonance images. The departure from zero of the differences between left and right hemispheres (L-R), a measure of directional asymmetry (DA), the variance of L-R, and an index of fluctuating asymmetry (FA) were evaluated for each region. Significant departures from perfect symmetry were found for most cortical gyri and sulci. Regions showed leftward asymmetry at the population level in the frontal lobe and superior lateral parts of the parietal lobe. Rightward asymmetry was found in the inferior parietal, occipital, frontopolar, and orbital regions, and the cingulate (anterior, middle, and posterior-ventral). Despite this general pattern, several sulci showed the opposite DA compared to the neighbouring gyri, which remarks the need to consider the neurobiological differences in gyral and sulcal development in the study of structural asymmetries. The results also confirm the absence of DA in most parts of the inferior frontal gyrus and the precentral region. This study contributes with data on populations underrepresented in the databases used in neurosciences. Among its findings, there is agreement with previous results obtained in populations of different ancestry and some discrepancies in the middle frontal and medial parietal regions. A significant DA not reported previously was found for the volume of long and short insular gyri and the central sulcus of the insula, frontomarginal, transverse frontopolar, paracentral, and middle and posterior parts of the cingulate gyrus and sulcus, gyrus rectus, occipital pole, and olfactory sulcus, as well as for the volume and area of the transverse collateral sulcus and suborbital sulcus. Also, several parcels displayed significant variability in the left-right differences, which can be partially attributable to developmental instability, a source of FA. Moreover, a few gyri and sulci displayed ideal FA with non-significant departures from perfect symmetry, such as subcentral and posterior cingulate gyri and sulci, inferior frontal and fusiform gyri, and the calcarine, transverse collateral, precentral, and orbital sulci. Overall, these results show that asymmetries are ubiquitous in the cerebral cortex.

Inter- and intrapopulation variability of dental tissue proportions of European and African modern human populations’ permanent canines

Inter- and intrapopulation variability of dental tissue proportions of European and African modern human populations’ permanent canines

Early male and female footprints of modern humans across Eurasia and Australasia.

As an alternative to a recent coastal southern route followed by modern humans to colonize Eurasia after an Out of Africa around 60 Kya, and under the premise that the evolutionary rate based coalescent ages slowdown going backwards in time, I propose a new model based on phylogenetic and phylogeographic analyses of uniparental markers in present and past modern human populations across Eurasia and Australasia. The archaeological record favors a northern route that reached China around 120 kya and then descended latitudinally reaching Southeast Asia and islands around 70-60 kya. These ages coincide with the basal split of the mtDNA macrohaplogroup L3’4* and the origin of the Y- chromosome macrohaplogroup CT* and the subsequent splits in Eurasia of mtDNA haplogroups M and N and Y-chromosome C, D and F clades respectively. Roughly at the same time modern humans arrived in Australasia other groups retreated southwest returning to Africa carrying with them mtDNA L3 and Y-Chromosome E lineages. Southeast Asia and Southwest-Central Asia were the subsequent demographic centers for the respective colonization of East and northern Asia and Europe. Across the Ganges-Brahmaputra and the Indus valleys, South Asia was colonized from both migratory centers.

A comprehensive review of HVS-I mitochondrial DNA variation of 19 Iranian populations.

Iran is located along the Central Asian corridor, a natural artery that has served as a cross-continental route since the first anatomically modern human populations migrated out of Africa. We compiled and reanalyzed the HVS-I (hypervariable segment-I) of 3840 mitochondrial DNA (mtDNA) sequences from 19 Iranian populations and from 26 groups from adjacent countries to give a comprehensive review of the maternal genetic variation and investigate the impact of historical events and cultural factors on the maternal genetic structure of modern Iranians. We conclude that Iranians have a high level of genetic diversity. Thirty-six haplogroups were observed in Iran's populations, and most of them belong to widespread West-Eurasian haplogroups, such as H, HV, J, N, T, and U. In contrast, the predominant haplogroups observed in most of the adjacent countries studied here are H, M, D, R, U, and C haplogroups. Using principal component analysis, clustering, and genetic distance-based calculations, we estimated moderate genetic relationships between Iranian and other Eurasian groups. Further, analyses of molecular variance and comparing geographic and genetic structures indicate that mtDNA HVS-I sequence diversity does not exhibit any sharp geographic structure in the country. Barring a few from some culturally distinct and naturally separated minorities, most Iranian populations have a homogenous maternal genetic structure.

Pharmacogenetic Variation in Neanderthals and Denisovans and Implications for Human Health and Response to Medications.

Modern humans carry both Neanderthal and Denisovan (archaic) genome elements that are part of the human gene pool and affect the life and health of living individuals. The impact of archaic DNA may be particularly evident in pharmacogenes-genes responsible for the processing of exogenous substances such as food, pollutants, and medications-as these can relate to changing environmental effects, and beneficial variants may have been retained as modern humans encountered new environments. However, the health implications and contribution of archaic ancestry in pharmacogenes of modern humans remain understudied. Here, we explore 11 key cytochrome P450 genes (CYP450) involved in 75% of all drug metabolizing reactions in three Neanderthal and one Denisovan individuals and examine archaic introgression in modern human populations. We infer the metabolizing efficiency of these 11 CYP450 genes in archaic individuals and find important predicted phenotypic differences relative to modern human variants. We identify several single nucleotide variants shared between archaic and modern humans in each gene, including some potentially function-altering mutations in archaic CYP450 genes, which may result in altered metabolism in living people carrying these variants. We also identified several variants in the archaic CYP450 genes that are novel and unique to archaic humans as well as one gene, CYP2B6, that shows evidence for a gene duplication found only in Neanderthals and modern Africans. Finally, we highlight CYP2A6, CYP2C9, and CYP2J2, genes which show evidence for archaic introgression into modern humans and posit evolutionary hypotheses that explain their allele frequencies in modern populations.

Leukocyte immunoglobulin-like receptor A3 gene deletion in five Chinese populations and protective association with nasopharyngeal carcinoma.

Among the thirteen leukocyte Ig-like receptor (LILR) loci located at 19q13.4, LILRA3 is unique in that it encodes a soluble protein lacking the transmembrane and cytoplasmic domains, and a 6.7 kb deletion spanning the first seven exons has been detected in some human individuals. Presently, there is a lack of data about the distribution of LILRA3 gene deletion in more diverse ethnic groups. Also, no previous studies have investigated the correlation between copy number variation (CNV) of LILRA3 and nasopharyngeal carcinoma (NPC). In this study, five populations from China mainland: two Southern Han populations, Hunan (N = 1478) and Guandong (N = 107); one Southeastern Han population, Fujian (N = 439); and two Northern populations, Inner Mongolia Han (N = 104) and Mongol population from Inner Mongolia (N = 158) were investigated for CNV of LILRA3 using polymerase chain reaction-sequence-specific priming (PCR-SSP) method. LILRA3 variants were also examined in a cohort of NPC cases (N = 1142) in Hunan Han population. The five Chinese populations demonstrated northward increase in frequency of the deleted form of LILRA3 gene (LILRA3*Del) (all corrected p values < 0.05). Inter-population comparison also uncovered significant differentiation in the distribution of CNV of LILRA3 among modern human populations. LILRA3*Del was found to confer significantly reduced risk to NPC in Hunan Han population (at allelic level: OR = 0.79, 95% CI = 0.71-0.89, p < 0.0001; at genotype level: OR= 0.63, 95% CI = 0.51-0.79, p < 0.0001). No interaction was found between LILRA3 variants and HLA-A*02:07, HLA-A*11:01, HLA-B*13 and HLA-B*46:01 alleles in susceptibility to NPC. Our study constitutes the first demonstration of LILRA3 gene as a locus linked to NPC susceptibility in a southern Chinese population. Future independent studies in other populations are warranted to confirm the findings reported in this study.