Search

Closely related species often have different sex-chromosome systems, but it is not known whether sex-chromosome turnover contributes to the evolution of reproductive isolation between species. Here, a neo-sex chromosome is identified in only one member of a sympatric species pair of stickleback fish in Japan. The newly evolved sex chromosome is found to contain genes that contribute to speciation, suggesting that sex-chromosome turnover might have a greater role in speciation than was previously appreciated.

Timothy Frayling, Joel Hirschhorn, Peter Visscher and colleagues report a meta-analysis of genome-wide association studies for adult height in 253,288 individuals. They identify 697 variants in 423 loci significantly associated with adult height and find that these variants cluster in pathways involved in growth and together explain one-fifth of the heritability for this trait.

Ruth Loos and colleagues report a meta-analysis of genome-wide association studies in 181,171 individuals identifying 14 new loci associated with heart rate and test these for association with cardiac conduction, rhythm disorders and cardiovascular disease. Their experimental studies in Drosophila melanogaster and zebrafish models provide support for a role for 20 candidate genes at 11 of these loci in regulation of heart rate.

Heribert Schunkert and colleagues report a meta-analysis of 14 genome-wide association studies of coronary disease (CAD) followed by replication in additional cohorts. They confirm 10 previously associated loci and identify 13 loci newly associated with CAD.

Cristen Willer and colleagues report genome-wide association analyses for blood lipid levels in 188,578 individuals. They identify 62 loci newly associated with blood lipid levels, refine the association signals at 12 loci and examine associations with cardiovascular and metabolic traits.

Panos Deloukas, Nilesh Samani and colleagues report a large-scale association analysis using the Metabochip array in 63,746 coronary artery disease cases and 130,681 controls. They identify 15 susceptibility loci, refine previous associations and use network analysis to highlight biological pathways.

The Tobacco and Genetics Consortium report meta-analyses of several smoking phenotypes across 16 cohorts including 74,053 individuals. They identify three loci associated with cigarettes smoked per day.

Ruth Loos and colleagues report results of a large genome-wide association study for body mass index. They identify 18 new loci associated with this trait, some of which map near key hypothalamic regulators of energy balance.

Sekar Kathiresan and colleagues examine 185 common variants using a modified mendelian randomization approach and provide evidence supporting a causal role of triglyceride-rich lipoproteins in the development of coronary artery disease.

The authors build recombination maps of marine, freshwater and hybrid sticklebacks at a scale of 3.8 kb, examining differences in recombination rates and evolutionary implications in populations undergoing adaptive divergence. They find evidence of recombination suppression in hybrids and reduced fitness of recombinants in a natural hybrid zone.

Integrating functional data with GWAS loci can help interpret the function of genetic variants associated with disease. Here the authors map cis and trans methylation QTL in CD4 + T cells from patients and colocalize with GWAS loci in order to interpret genetic variants associated with multiple sclerosis.

Epigenetic clocks based on DNA methylation levels are estimators of chronological age. Here, the authors perform a GWAS of epigenetic aging rates in blood and find SNP variants in the TERT locus associated with increased intrinsic epigenetic age are also associated with longer telomeres.

Erik Ingelsson and colleagues report a large-scale genome-wide meta-analysis for associations to the extremes of anthropometric traits, including body mass index, height, waist-to-hip ratio and clinical obesity. They identify four loci newly associated with height and seven loci newly associated with clinical obesity and find overlap in the genetic structure and distribution of variants identified for these extremes of the trait distributions and for the general population.

Cecilia Lindgren and colleagues report results of a large-scale genome-wide association study for waist-to-hip ratio, a measure of body fat distribution. They identify 13 new loci associated with this trait, several of which show stronger effects in women than in men.

A genome-wide association study and Metabochip meta-analysis of body mass index (BMI) detects 97 BMI-associated loci, of which 56 were novel, and many loci have effects on other metabolic phenotypes; pathway analyses implicate the central nervous system in obesity susceptibility and new pathways such as those related to synaptic function, energy metabolism, lipid biology and adipogenesis.

Patricia Munroe, Christopher Newton-Cheh, Andrew Morris and colleagues perform association studies in over 340,000 individuals of European ancestry and identify 66 loci, of which 17 are novel, involved in blood pressure regulation. The risk SNPs are enriched for cis-regulatory elements, particularly in vascular endothelial cells.

Genome-wide association meta-analyses of waist-to-hip ratio adjusted for body mass index in more than 224,000 individuals identify 49 loci, 33 of which are new and many showing significant sexual dimorphism with a stronger effect in women; pathway analyses implicate adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution.

Abnormal blood lipid levels are important risk factors for cardiovascular and other various diseases. Here the authors conduct a large-scale multi-ethnic epigenome-wide association study combined with epigenetic (cis-QTL and eQTM) data, and identify CpG-lipid traits associations that are specific to or common across racial/ethnic groups.

Cd4 expression in helper and cytotoxic T cells is locked in by gene-expression programs that define lineage identity. Littman and colleagues define stage-specific methylation and demethylation events that regulate the heritable expression of Cd4.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

This very large genome-wide association study identifies hundreds of new genetic variants influencing adult height in at least 180 loci enriched for genes involved in skeletal growth defects. The results show that the likely causal gene is often located near the most strongly associated variant, that many loci have multiple independently associated variants and that associated variants are enriched for likely functional effects on genes.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

With a comprehensive analysis of sequencing data, DNA copy number, gene expression and DNA methylation in a large number of human glioblastomas, The Cancer Genome Atlas project initiative provides a broad overview of the genes and pathways that are altered in this cancer type.

Joanna Howson and colleagues perform a genome-wide association study and meta-analysis for coronary artery disease in large, trans-ancestry cohorts. They identify 15 new loci and correlate these regions with cell-type-specific gene expression and plasma protein levels to find novel pathways and potential mechanisms of disease.

Better analytical methods are needed to extract biological meaning from genome-wide association studies (GWAS) of psychiatric disorders. Here the authors take GWAS data from over 60,000 subjects, including patients with schizophrenia, bipolar disorder and major depression, and identify common etiological pathways shared amongst them.

Lars Forsberg, Jan Dumanski and colleagues report that age-related loss of chromosome Y in peripheral blood is associated with increased risks of all-cause mortality, cancer mortality and non-hematological cancer mortality.

Germline mutation rate is a critical parameter in the study of genetics and evolution. Here, Carlson et al. infer fine-scale patterns of human mutation rate heterogeneity by analyzing ~36 million singleton variants from 3560 whole-genome sequences.

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.

Naomi Wray and colleagues report an analysis of genome-wide association data sets from the Psychiatric Genomics Consortium for five psychiatric disorders. They find that common variation explains 17–29% of the variance in liability and provide further support for a shared genetic etiology for these related psychiatric disorders.

The Psychiatric GWAS Consortium Bipolar Disorder Working Group reports a large-scale genome-wide association study of 7,481 individuals with bipolar disorder with replication in 4,493 cases. The Consortium identifies a new susceptibility locus near ODZ4 and replicates a known association near CACNA1C for bipolar disorder.

Simone de Jong et al. examine the balance of common and rare risk for psychiatric disorders in a large family with high incidence of Bipolar Disorder and Major Depressive Disorder. They find that increased polygenic risk over generations could be partially due to assortative mating, which may explain the observation of anticipation in mood disorders.