Interest in reconstructing demographic histories has motivated the development of methods to estimate locus-specific pairwise coalescence times from whole-genome sequencing data. Here we introduce a powerful new method, ASMC, that can estimate coalescence times using only SNP array data, and is orders of magnitude faster than previous approaches. We applied ASMC to detect recent positive selection in 113,851 phased British samples from the UK Biobank, and detected 12 genome-wide significant signals, including 6 novel loci. We also applied ASMC to sequencing data from 498 Dutch individuals to detect background selection at deeper time scales. We detected strong heritability enrichment in regions of high background selection in an analysis of 20 independent diseases and complex traits using stratified linkage disequilibrium score regression, conditioned on a broad set of functional annotations (including other background selection annotations). These results underscore the widespread effects of background selection on the genetic architecture of complex traits.
Annexins: the problem of assessing the biological role for a gene family of multifunctional calcium- and phospholipid-binding proteins
TAFA: a novel secreted family with conserved cysteine residues and restricted expression in the brain
Genomic relationships and speciation times of human, chimpanzee, and gorilla inferred from a coalescent hidden Markov model
A single SNP in an evolutionary conserved region within intron 86 of the HERC2 gene determines human blue-brown eye color
Association of STAT4 with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in the Japanese population
A flexible and accurate genotype imputation method for the next generation of genome-wide association studies
Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
Interaction between PKD1L3 and PKD2L1 through their transmembrane domains is required for localization of PKD2L1 at taste pores in taste cells of circumvallate and foliate papillae
Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population
Inference of recombination maps from a single pair of genomes and its application to ancient samples
Concerted variation of the 3' regulatory region of Ig heavy chain and Gm haplotypes across human continental populations
Genome-Wide Natural Selection Signatures Are Linked to Genetic Risk of Modern Phenotypes in the Japanese Population.
Identity-by-descent detection across 487,409 British samples reveals fine scale population structure and ultra-rare variant associations.
BioHub - Researcher Network
The Chan-Zuckerberg Biohub aims to support the fundamental research and develop the technologies that will enable physicians to cure, prevent, or manage all diseases in our childrens' lifetimes. The CZ Biohub brings together researchers from UC Berkeley, Stanford, and UCSF. Find the latest research from the CZ Biohub researcher network here.