The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.

Obesity is globally prevalent and highly heritable, but the underlying genetic factors remain largely elusive. To identify genetic loci for obesity-susceptibility, we examined associations between body mass index (BMI) and ~2.8 million SNPs in up to 123,865 individuals, with targeted follow-up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity-susceptibility loci and identified 18 new loci associated with BMI (P<5×10−8), one of which includes a copy number variant near GPRC5B. Some loci (MC4R, POMC, SH2B1, BDNF) map near key hypothalamic regulators of energy balance, and one is near GIPR, an incretin receptor. Furthermore, genes in other newly-associated loci may provide novel insights into human body weight regulation.

Summary: Genome-wide association studies (GWAS) have revealed hundreds of loci associated with common human genetic diseases and traits. We have developed a web-based plotting tool that provides fast visual display of GWAS results in a publication-ready format. LocusZoom visually displays regional information such as the strength and extent of the association signal relative to genomic position, local linkage disequilibrium (LD) and recombination patterns and the positions of genes in the region.Availability: LocusZoom can be accessed from a web interface at http://csg.sph.umich.edu/locuszoom. Users may generate a single plot using a web form, or many plots using batch mode. The software utilizes LD information from HapMap Phase II (CEU, YRI and JPT+CHB) or 1000 Genomes (CEU) and gene information from the UCSC browser, and will accept SNP identifiers in dbSNP or 1000 Genomes format. Single plots are generated in ∼20 s. Source code and associated databases are available for download and local installation, and full documentation is available online.Contact: cristen@umich.edu