Iain Mathieson
A5063643733- Forensic and Genetic Research
- Genetic Associations and Epidemiology
- Genetic diversity and population structure
- Genetic and phenotypic traits in livestock
- Evolution and Genetic Dynamics
- Genomics and Rare Diseases
- Race, Genetics, and Society
- Forensic Anthropology and Bioarchaeology Studies
- Genetic Mapping and Diversity in Plants and Animals
- Yersinia bacterium, plague, ectoparasites research
- Genomics and Phylogenetic Studies
- Archaeology and ancient environmental studies
- Nutrition, Genetics, and Disease
- Molecular Biology Techniques and Applications
- Cellular transport and secretion
- Genomics and Chromatin Dynamics
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Identification and Quantification in Food
- Genetics, Bioinformatics, and Biomedical Research
- Genomic variations and chromosomal abnormalities
- Machine Learning in Bioinformatics
- Genetics and Neurodevelopmental Disorders
- RNA and protein synthesis mechanisms
- melanin and skin pigmentation
- Zoonotic diseases and public health
University of Pennsylvania
2018-2025
California University of Pennsylvania
2022-2023
Harvard University
2014-2020
Boston VA Research Institute
2020
Centre for Human Genetics
2011-2017
University of Oxford
2011-2017
Science Oxford
2012
University of Louisville Hospital
1996
The contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7×) or exomes (high 80×) nearly 10,000 individuals population-based disease collections. In extensively phenotyped cohorts characterize over 24 million novel sequence variants, generate a highly accurate imputation reference panel identify alleles associated with levels triglycerides (APOB), adiponectin (ADIPOQ) low-density...
Given the anthropometric differences between men and women previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip waist-to-hip-ratio (133,723 individuals) took forward 348 SNPs into follow-up (additional 137,052 total 94 studies. Seven loci displayed significant (FDR<5%), including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA,...
Genetic predictions of height differ among human populations and these differences have been interpreted as evidence polygenic adaptation. These were first detected using SNPs genome-wide significantly associated with height, shown to grow stronger when large numbers sub-significant included, leading excitement about the prospect analyzing fractions genome detect adaptation for multiple traits. Previous studies based on SNP effect size measurements in GIANT Consortium meta-analysis. Here we...
Abstract Polycystic ovary syndrome (PCOS) is the most common reproductive disorder in women, yet there little consensus regarding its aetiology. Here we perform a genome-wide association study of PCOS up to 5,184 self-reported cases White European ancestry and 82,759 controls, with follow-up further ∼2,000 clinically validated ∼100,000 controls. We identify six signals for at statistical significance ( P <5 × 10 −8 ), in/near genes ERBB4/HER4 , YAP1 THADA FSHB RAD50 KRR1. Variants three...
Archaeogenetic studies have described the formation of Eurasian 'steppe ancestry' as a mixture Eastern and Caucasus hunter-gatherers. However, it remains unclear when where this ancestry arose whether was related to horizon cultural innovations in 4th millennium BCE that subsequently facilitated advance pastoral societies Eurasia. Here we generated genome-wide SNP data from 45 prehistoric individuals along 3000-year temporal transect North Caucasus. We observe genetic separation between...
Germline mutation determines rates of molecular evolution, genetic diversity, and fitness load. In humans, the average point rate is 1.2 × 10(-8) per base pair generation, with every additional year father's age contributing two mutations across genome males three to four times as many females. To assess whether such patterns are shared our closest living relatives, we sequenced genomes a nine-member pedigree Western chimpanzees, Pan troglodytes verus. Our results indicate but male...
Variation at the FADS1/FADS2 gene cluster is functionally associated with differences in lipid metabolism and often hypothesized to reflect adaptation an agricultural diet. Here, we test evidence for this relationship using both modern ancient DNA data. We show that almost all inhabitants of Europe carried ancestral allele until derived was introduced ∼8,500 years ago by Early Neolithic farming populations. However, also it not under strong selection these find allele, other proposed...
Inferring the nature and magnitude of selection is an important problem in many biological contexts. Typically when estimating a coefficient for allele, it assumed that samples are drawn from panmictic population acts uniformly across population. However, these assumptions rarely satisfied. Natural populations almost always structured, selective pressures likely to act differentially. Inference about ought therefore take account structure. We do this by considering evolution simple lattice...
Ancestry connects genetics and society in fundamental ways.For many people it has cultural, religious or even political significance, can play a key role shaping personal public identities.People's desire to discover their own ancestry drives the multibillion-dollar genealogy industry, which grown rapidly era of consumer genomics.Companies such as 23andMe now claim tens millions customers worldwide.In parallel, our scientific understanding human past is being transformed by studies ancient...
Large whole-genome sequencing projects have provided access to much rare variation in human populations, which is highly informative about population structure and recent demography. Here, we show how the age of variants can be estimated from patterns haplotype sharing these ages related historical relationships between populations. We investigate distribution occurring exactly twice ( variants) a worldwide sample sequenced by 1000 Genomes Project, revealing enormous across The median...
Population stratification continues to bias the results of genome-wide association studies (GWAS). When these are used construct polygenic scores, even subtle biases can cumulatively lead large errors. To study effect residual stratification, we simulated GWAS under realistic models demographic history. We show that when population structure is recent, it cannot be corrected using principal components common variants because they uninformative about recent Consequently, scores biased in...
Mutations occur at vastly different rates across the genome, and populations, leading to differences in spectrum of segregating polymorphisms. Here, we investigate variation rare variant a sample human genomes representing all major world populations. We find least two distinct signatures variation. One, consistent with previously reported signature is characterized by an increased rate TCC>TTC mutations people from Western Eurasia South Asia, likely related rate, or efficiency repair,...
The genetic diversity of humans, like many species, has been shaped by a complex pattern population separations followed isolation and subsequent admixture. This pattern, reaching at least as far back the appearance our species in paleontological record, left its traces genomes. Reconstructing population's history from these is challenging problem. Here we present novel approach based on Multiple Sequentially Markovian Coalescent (MSMC) to analyze separation between populations. Our...
Polygenic risk scores (PRS) use the results of genome-wide association studies (GWAS) to predict quantitative phenotypes or disease at an individual level, and provide a potential route genetic data in personalized medical care. However, major barrier PRS is that majority GWAS come from cohorts European ancestry. The predictive power constructed these substantially lower non-European ancestry cohorts, although reasons for this are unclear. To address question, we investigate performance...