Tools Population Genetics Ancient DNA

AncientProxy is a catalog of ancient proxies for modern genetic variants, directly bridging aDNA and GWAS. It quantifies LD between modern GWAS variants and ancient genotyped variants (AGVs from AADR) — 260,732,675 variant pairs. At R2 >= 0.9, it covers >=60% of common GWAS variants in non-Africans and 34% in Africans — 5.6x more coverage than using AGVs alone.

Ancient DNA (aDNA) has the potential to illuminate the evolutionary history of human complex traits and diseases. However, a major limitation is that most aDNA datasets contain fewer than 1.5 million single-nucleotide polymorphisms (SNPs), which cover only a small fraction of the variants identified in genome-wide association studies (GWAS). Here, we introduce AncientProxy, a catalog that quantifies linkage disequilibrium between modern GWAS variants and ancient genotyped variants (AGVs) to identify proxies for modern variants in aDNA datasets. We estimated LD between over 260 million variant pairs and found that at an R2 threshold of 0.9, ancient proxies cover at least 60% of common GWAS variants in non-African populations and 34% in African populations, a 5.6-fold increase over using AGVs alone. AncientProxy enables researchers to expand the range of complex traits and diseases that can be studied with aDNA.

The Allen Ancient DNA Resource (AADR) is the premier curated compendium of ancient human genomes. It provides uniformly processed, publicly available genotype data from thousands of ancient and present-day individuals at up to ~1.23 million SNP positions (1240K capture + genome-wide). The most widely used aDNA resource in human paleogenomics. Persistent dataset ID: doi:10.7910/DVN/FFIDCW.

The Allen Ancient DNA Resource (AADR) is a curated compendium of published ancient human genomes. It includes genome-wide data from over 10,000 ancient individuals, genotyped at up to ~1.23 million single nucleotide polymorphism positions. The dataset is publicly available and regularly updated, providing a standardized resource for paleogenomic research.

Foundational review on quantitative paleogenetics — using ancient DNA (aDNA) to study complex trait evolution. Covers polygenic score applications in ancient samples, detection of natural selection on complex traits, methods for linking aDNA to GWAS findings, and critical limitations including ascertainment bias, genetic drift confounding, and the challenge of inferring past phenotypes from genotype data alone.

The field of human paleogenetics has entered a new era, with the availability of genome-scale ancient DNA (aDNA) datasets that span tens of thousands of years. These data provide a unique opportunity to directly study how complex trait architectures have evolved over time. In this review, we discuss the methods and challenges of using aDNA to study complex trait evolution, including the use of polygenic scores, the detection of selection on complex traits, and the limitations of current approaches.

Comprehensive review by Iain Mathieson on using ancient DNA (aDNA) for polygenic prediction of human complex traits. Covers methodology for applying GWAS-derived polygenic scores to ancient samples, discusses limitations including selection bias, population structure, and genotype-phenotype mapping across time, and summarizes key findings from the paleogenomic literature.

Ancient DNA (aDNA) provides a direct window into the genetic history of human populations. Recent advances have made it possible to apply polygenic scores, derived from modern GWAS, to ancient individuals, allowing us to study how the genetic architecture of complex traits has changed over time. In this review, I discuss the methods used to predict polygenic traits from aDNA, the biological insights gained, and the limitations and challenges that remain.

Large-scale detection of natural selection using aDNA time-series data. Analyzed 8,433 ancient West Eurasians spanning 14,000 years and 6,510 present-day individuals. Found 347 selection loci and examined selection on polygenic traits including body fat, pigmentation, schizophrenia risk, and cognitive performance. Directly relevant to understanding how selection shapes complex trait architecture.

Ancient DNA (aDNA) time-series data provide a direct way to study natural selection. Here we analyzed 14,000 years of human genomes from West Eurasia, combining 8,433 ancient and 6,510 present-day individuals. We identified 347 loci under strong directional selection, most of which were previously unknown. We examined the effects of selection on polygenic traits, showing that selection has shaped body fat, pigmentation, and other complex traits over time. Our results demonstrate the power of aDNA to realize the promise of understanding human adaptation.