Multiple studies have confirmed the contribution of rare de novo copy number variations to
the risk for autism spectrum disorders 1 , 2 , 3 . But whereas de novo single nucleotide …

A major goal in human genetics is to use natural variation to understand the phenotypic
consequences of altering each protein-coding gene in the genome. Here we used exome …

Congenital heart disease (CHD) is the most frequent birth defect, affecting 0.8% of live births
1 . Many cases occur sporadically and impair reproductive fitness, suggesting a role for de …

Estimates from genome-wide association studies (GWAS) of unrelated individuals capture
effects of inherited variation (direct effects), demography (population stratification, assortative …

Osteoarthritis affects over 300 million people worldwide. Here, we conduct a genome-wide
association study meta-analysis across 826,690 individuals (177,517 with osteoarthritis) and …

Background Loss-of-function variants in the angiopoietin-like 3 gene (ANGPTL3) have been
associated with decreased plasma levels of triglycerides, low-density lipoprotein (LDL) …

We report genomic analysis of 300 meningiomas, the most common primary brain tumors,
leading to the discovery of mutations in TRAF7, a proapoptotic E3 ubiquitin ligase, in nearly …

Background Elucidation of the genetic factors underlying chronic liver disease may reveal
new therapeutic targets. Methods We used exome sequence data and electronic health …

Adrenal aldosterone-producing adenomas (APAs) constitutively produce the salt-retaining
hormone aldosterone and are a common cause of severe hypertension. Recurrent mutations …

INTRODUCTION Large-scale genetic studies of integrated health care populations, with
phenotypic data captured natively in the documentation of clinical care, have the potential to …