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Gil McVean and Iain Mathieson report an analysis of the differential effects of population stratification on rare and common variants within association studies. They find that rare variants may show stronger stratification in some situations and that this is not corrected for by current structure methods, suggesting the need for the development of new statistical methods.

Mathieson et al. carried out a genome-wide association study of reproductive success (number of children born) in humans, revealing the importance of diverse neuro-endocrine and behavioural factors.

Deep whole-genome sequencing of 300 individuals from 142 diverse populations provides insights into key population genetic parameters, shows that all modern human ancestry outside of Africa including in Australasians is consistent with descending from a single founding population, and suggests a higher rate of accumulation of mutations in non-Africans compared to Africans since divergence.

The first genome-wide scan for selection using ancient DNA, based on data from 230 West Eurasians dating between to 6500 and 300 bc and including new data from 163 individuals among which are 26 Neolithic Anatolians, provides a direct view of selection on loci associated with diet, pigmentation and immunity.

Evidence from genetics, skeletal remains and dietary isotopes indicates that sex-specific height disparities in Early Neolithic Europe can be linked to culture, more than environment or genetics. This suggests that a cultural preference for males may have had biological effects 7,000 yr ago.

The Caucasus mountain range has impacted on the culture and genetics of the wider region. Here, the authors generate genome-wide SNP data for 45 Eneolithic and Bronze Age individuals across the Caucasus, and find distinct genetic clusters between mountain and steppe zones as well as occasional gene-flow.

Analysis of ancient genomic data of 51 humans from Eurasia dating from 45,000 to 7,000 years ago provides insight into the population history of pre-Neolithic Europe and support for recurring migration and population turnover in Europe during this period.

This paper describes the largest genome-wide association study to date on polycystic ovary syndrome (PCOS), a common reproductive disorder in women. Six genetic loci—including known targets of cancer chemotherapy—were identified, and the authors infer causal and balancing selection mechanisms involved in PCOS risk and susceptibility.

Genome-wide ancient DNA data from 225 individuals who lived in southeastern Europe between 12000 and 500 bc reveals that the region acted as a genetic crossroads before and after the arrival of farming.

Levels of circulating thyrotropin and free thyroxine reflect thyroid function, however, their genetic underpinnings remain poorly understood. Taylor et al. take advantage of whole-genome sequence data from cohorts within the UK10K project to identify novel variants associated with these traits.

1000 Genomes imputation can increase the power of genome-wide association studies to detect genetic variants associated with human traits and diseases. Here, the authors develop a method to integrate and analyse low-coverage sequence data and SNP array data, and show that it improves imputation performance.

Imputation uses genotype information from SNP arrays to infer the genotypes of missing markers. Here, the authors show that an imputation reference panel derived from whole-genome sequencing of 3,781 samples from the UK10K project improves the imputation accuracy and coverage of low frequency variants compared to existing methods.

Population-based genome sequencing provides an increasingly rich resource for the identification of low-frequency, large effect variants associated with clinically important phenotypes. Timpson et al. use UK10K data to identify a variant of the APOC3gene strongly associated with plasma triglyceride levels.

This report from the 1000 Genomes Project describes the genomes of 1,092 individuals from 14 human populations, providing a resource for common and low-frequency variant analysis in individuals from diverse populations; hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites, can be found in each individual.

Size and shape of the brain are, among others, influenced by the dimensions of the skull. Here, the authors report genome-wide association studies for head circumference and intracranial volume in children and adults and the identification of nine common or low-frequency variants associated with these traits.

Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics.

Low read depth sequencing of whole genomes and high read depth exomes of nearly 10,000 extensively phenotyped individuals are combined to help characterize novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with lipid-related traits; in addition to describing population structure and providing functional annotation of rare and low-frequency variants the authors use the data to estimate the benefits of sequencing for association studies.

Gerton Lunter and colleagues report Platypus software, which combines a haplotype-based multi-sample variant caller with local sequence assembly in a Bayesian statistical framework. They demonstrate applications to exome and whole-genome data sets, to the identification de novo mutations in parent-offspring trios and to the genotyping of HLA loci.

Using whole-genome data for single-nucleotide polymorphism and results from genome-wide association studies, the authors show that people’s preference for pairing with those with similar phenotypic traits has genetic causes and consequences.