Large-scale reference data sets of human genetic variation are critical for the medical and
functional interpretation of DNA sequence changes. Here we describe the aggregation and …

Genetic variants that inactivate protein-coding genes are a powerful source of information
about the phenotypic consequences of gene disruption: genes that are crucial for the function …

Both polygenicity (many small genetic effects) and confounding biases, such as cryptic
relatedness and population stratification, can yield an inflated distribution of test statistics in …

Identifying genetic correlations between complex traits and diseases can provide useful
etiological insights and help prioritize likely causal relationships. The major challenges …

Background Cancers arise from multiple acquired mutations, which presumably occur over
many years. Early stages in cancer development might be present years before cancers …

Recent work has demonstrated that some functional categories of the genome contribute
disproportionately to the heritability of complex diseases. Here we analyze a broad set of …

Rare coding variation has historically provided the most direct connections between gene
function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 …

Attention deficit/hyperactivity disorder (ADHD) is a highly heritable childhood behavioral
disorder affecting 5% of children and 2.5% of adults. Common genetic variants contribute …

Autism spectrum disorders (ASD) are believed to have genetic and environmental origins,
yet in only a modest fraction of individuals can specific causes be identified 1 , 2 . To identify …

Polygenic risk scores (PRS) are poised to improve biomedical outcomes via precision medicine.
However, the major ethical and scientific challenge surrounding clinical implementation …