Featured
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| Open AccessTrans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies
Estimated glomerular filtration rate (eGFR) is a measure of kidney function used to define chronic kidney disease. Here, Morris et al. perform trans-ethnic genome-wide meta-analyses for eGFR in 312,468 individuals and identify novel loci and downstream putative causal genes.
- Andrew P. Morris
- , Thu H. Le
- & Nora Franceschini
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Article
| Open AccessGenome wide association analysis in a mouse advanced intercross line
Multigenerational outbred populations from an advanced intercross line (AIL) of mice represent useful resources for genome wide association analysis. Here, the authors analyze 1,063 LG x SM AIL mice to identify significant associations for 50 traits relevant to human health and disease.
- Natalia M. Gonzales
- , Jungkyun Seo
- & Abraham A. Palmer
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Article
| Open AccessA common genetic mechanism underlies morphological diversity in fruits and other plant organs
Remarkable organ shape morphological diversity exists in fruits, vegetables and seeds. Here, the authors establish a link between OVATE Family Proteins and TONNEAU1 Recruiting Motif family proteins in the development pathway that governs fruit shape of tomato, melon, and cucumber as well as potato tuber shape.
- Shan Wu
- , Biyao Zhang
- & Esther van der Knaap
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Article
| Open AccessGenome‐wide mapping of plasma protein QTLs identifies putatively causal genes and pathways for cardiovascular disease
Genetic variation can influence levels of disease-related plasma proteins and, thus, contribute to the pathogenesis of complex diseases. Here, the authors perform genome-wide QTL analysis for 71 plasma proteins to identify causal proteins for coronary heart disease and provide a molecular QTL browser.
- Chen Yao
- , George Chen
- & Daniel Levy
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Article
| Open AccessA mapping framework of competition–cooperation QTLs that drive community dynamics
Genetic variation from coexisting species influences interspecific interactions in a community. Here, the authors develop a framework for identifying quantitative trait loci (QTLs) underlying community dynamics and validate the tool using data from co-culturing of two bacterial species.
- Libo Jiang
- , Xiaoqing He
- & Rongling Wu
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Article
| Open AccessStudy of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
Cognitive function is associated with health and important life outcomes. Here, the authors perform a genome-wide association study for general cognitive function in 300,486 individuals and identify genetic loci that implicate neural and cell developmental pathways in this trait.
- Gail Davies
- , Max Lam
- & Ian J. Deary
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Article
| Open AccessA joint view on genetic variants for adiposity differentiates subtypes with distinct metabolic implications
In GWAS, waist-to-hip ratio (WHR) is often adjusted for body mass index (BMI) to account for their correlation (WHRadjBMI). Here, Winkler et al. classify 159 genetic variants for BMI, WHR, or WHRadjBMI based on their effect directions for BMI and WHR to differentiate subtypes of adiposity genetics.
- Thomas W Winkler
- , Felix Günther
- & Iris M Heid
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Article
| Open AccessImproving genetic prediction by leveraging genetic correlations among human diseases and traits
Genetic prediction of complex traits so far has limited accuracy because of insufficient understanding of the genetic risk. Here, Maier et al. develop an improved method for trait prediction that makes use of genetic correlations between traits and apply it to summary statistics of psychiatric diseases.
- Robert M. Maier
- , Zhihong Zhu
- & Matthew R. Robinson
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Article
| Open AccessGene-by-environment interactions in urban populations modulate risk phenotypes
Individuals with different genotypes may respond differently to environmental variation. Here, Favé et al. find substantial impacts of different environment exposures on the transcriptome and clinical endophenotypes when controlling for genetic ancestry by analyzing data from ∼1000 individuals from a founder population in Quebec.
- Marie-Julie Favé
- , Fabien C. Lamaze
- & Philip Awadalla
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Article
| Open AccessItem-level analyses reveal genetic heterogeneity in neuroticism
Neuroticism can be assessed as a composite score of individual items. Here, Nagel et al. perform genetic association studies for 12 neuroticism items and the sum-score and demonstrate genetic heterogeneity at the item-level.
- Mats Nagel
- , Kyoko Watanabe
- & Sophie van der Sluis
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Article
| Open AccessCo-occurring expression and methylation QTLs allow detection of common causal variants and shared biological mechanisms
Most expression QTLs (eQTLs) co-occur with a DNA methylation QTL (meQTL), suggesting a common causal variant. Here the authors analyse DNA and RNA from blood and identify eQTL-meQTL pairs likely to share a causal variant, finding that expression and methylation are often genetically co-regulated.
- Brandon L. Pierce
- , Lin Tong
- & Habibul Ahsan
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Review Article
| Open AccessFormalising recall by genotype as an efficient approach to detailed phenotyping and causal inference
Recall-by-Genotype (RbG) is an approach to recall participants from genetic studies based on their specific genotype for further, more extensive phenotyping. Here, the authors discuss examples of RbG as well as practical and ethical considerations and provide an online tool to aid in designing RbG studies.
- Laura J. Corbin
- , Vanessa Y. Tan
- & Nicholas J. Timpson
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Article
| Open AccessProtein quantitative trait locus study in obesity during weight-loss identifies a leptin regulator
Although many genetic variants are known for obesity, their function remains largely unknown. Here, in a weight-loss intervention cohort, the authors identify protein quantitative trait loci associated with BMI at baseline and after weight loss and find FAM46A to be a regulator of leptin in adipocytes.
- Jérôme Carayol
- , Christian Chabert
- & Jörg Hager
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Article
| Open AccessThe effect of genetic variation on promoter usage and enhancer activity
Expression quantitative trait loci (eQTL) are widely studied, yet the mechanisms by which they exert their effects are largely unknown. Here, performing CAGE-seq on 154 lymphoblastoid cell lines, the authors map regulatory variants associated with promoter usage (puQTLs) and enhancer activity (eaQTLs).
- Marco Garieri
- , Olivier Delaneau
- & Alexandre Fort
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Article
| Open AccessGenome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity
Variability in human longevity is genetically influenced. Using genetic data of parental lifespan, the authors identify associations at HLA-DQA/DRB1 and LPA and find that genetic variants that increase educational attainment have a positive effect on lifespan whereas increasing BMI negatively affects lifespan.
- Peter K. Joshi
- , Nicola Pirastu
- & James F. Wilson
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Article
| Open AccessCNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits
Individual SNPs have small effects on anthropometric traits, yet the impact of CNVs has remained largely unknown. Here, Kutalik and co-workers perform a large-scale genome-wide meta-analysis of structural variation and find rare CNVs associated with height, weight and BMI with large effect sizes.
- Aurélien Macé
- , Marcus A. Tuke
- & Zoltán Kutalik
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Article
| Open AccessThe genetic basis of natural variation in a phoretic behavior
Nematodes use a characteristic set of movements, called nictation, to hitchhike on more mobile animals. Here, Lee et al. identify a genetic locus in the nematode Caenorhabditis elegans that underlies nictation and contributes to successful hitchhiking, but at expense of reduced offspring production.
- Daehan Lee
- , Heeseung Yang
- & Junho Lee
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Article
| Open AccessA complete tool set for molecular QTL discovery and analysis
Analysis of molecular quantitative trait loci (molQTL) can help interpret genome-wide association studies and requires efficient approaches to correct for multiple testing. This study describes a bioinformatics toolkit called QTLtool that can handle large data sets and quickly perform multiple types of molQTL analyses.
- Olivier Delaneau
- , Halit Ongen
- & Emmanouil T. Dermitzakis
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Article
| Open AccessGenome-wide identification of splicing QTLs in the human brain and their enrichment among schizophrenia-associated loci
Alternative splicing of mRNAs occurs in tissue specific manners and may be modulated by genetic variations. Here, Takata and colleagues perform splicing quantitative trait loci analysis (sQTL) of human brain and show significant enrichment of sQTLs among neurological disease-associated loci.
- Atsushi Takata
- , Naomichi Matsumoto
- & Tadafumi Kato
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Article
| Open AccessTransient structural variations have strong effects on quantitative traits and reproductive isolation in fission yeast
Fission yeastSchizosaccharomyces pombe has diverse traits. Jeffares et al. characterize large copy number variations (CNVs) and rearrangements in S. pombe, and show that CNVs are transient with effects on quantitative traits and gene expression, whereas rearrangements influence intrinsic reproductive isolation.
- Daniel C. Jeffares
- , Clemency Jolly
- & Fritz J. Sedlazeck
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Article
| Open AccessPowerful decomposition of complex traits in a diploid model
Dissecting the architecture of complex trait is challenging. Here, Hallin, Märtens et al. devises Phased Outbred Lines (POLs) in order to accurately decompose growth trait variation in diploid yeast across different environments.
- Johan Hallin
- , Kaspar Märtens
- & Gianni Liti
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Article
| Open AccessGenetic linkage of distinct adaptive traits in sympatrically speciating crater lake cichlid fish
Genetic linkage of ecologically relevant traits has been suggested to facilitate sympatric speciation. Here, Fruciano et al. show in sister species of cichlid fish the genetic non-independence of genomic regions responsible for differentiation in body size and pharyngeal jaw morphology, two characters associated with adaptive divergence in sympatry.
- Carmelo Fruciano
- , Paolo Franchini
- & Axel Meyer
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Article
| Open AccessA heavy metal P-type ATPase OsHMA4 prevents copper accumulation in rice grain
Copper (Cu) is an essential mineral nutrient but high concentrations in rice grain can cause toxicity. Here the authors provide evidence that natural variation in rice grain Cu concentration is caused by altered sequestration of Cu into root vacuoles due to a single amino acid substitution in the OsHMA4 transporter.
- Xin-Yuan Huang
- , Fenglin Deng
- & Jian Feng Ma
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Article |
Genome-wide analysis in Drosophila reveals age-specific effects of SNPs on fitness traits
Senescence is the decline in physiological function associated with age, and the genetic basis of this phenomenon is poorly understood. Here, the authors identify genetic variants in Drosophilathat affect reproduction and lifespan in an age-specific manner, and provide support for the mutation accumulation theory of aging.
- Mary F. Durham
- , Michael M. Magwire
- & Jeff Leips
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Article
| Open AccessGenome-wide association mapping reveals a rich genetic architecture of complex traits in Oryza sativa
Understanding the genetics and physiology of domesticated species is important for crop improvement. By studying natural variation and the phenotypic traits of 413 diverse accessions of rice, Zhao et al. identify many common genetic variants that influence quantitative traits such as seed size and flowering time.
- Keyan Zhao
- , Chih-Wei Tung
- & Susan R. McCouch