Quantitative trait

  • Article
    | Open Access

    Modular, rather than integrated systems are classically thought to allow functional diversity to evolve rapidly. A study of cichlid fish shows integration between divergent jaw systems at the phylogenetic, population, and genetic scales, suggesting integration can and does facilitate rapid, coordinated trait evolution.

    • Andrew J. Conith
    •  & R. Craig Albertson
  • Article
    | Open Access

    Estimating direct and indirect effects of genotypes on phenotypes is important for genetic analyses such as Mendelian randomization. Here the authors compare five different methods to estimate direct and indirect genetic effects using summary results statistics that account for sample overlap.

    • Nicole M. Warrington
    • , Liang-Dar Hwang
    •  & David M. Evans
  • Article
    | Open Access

    Genetic plasticity drives phenotypic differences. Here, the authors develop a framework to quantify the individual and combinatorial contributions of SNPs on a phenotype of interest and use it to identify SNP-SNP interactions associated with variations in bacteria’s response to external changes.

    • Dengcheng Yang
    • , Yi Jin
    •  & Rongling Wu
  • Article
    | Open Access

    The authors provide a comprehensive, single base resolution view of association between genetic variation and DNA methylation in human brain. They also show that heritability attributed to schizophrenia GWAS-associated variants reflects the epigenetic plasticity of the brain.

    • Kira A. Perzel Mandell
    • , Nicholas J. Eagles
    •  & Andrew E. Jaffe
  • Article
    | Open Access

    Existing genetic prediction tools typically assume that genetic variants contribute equally towards the phenotype. The authors develop eight prediction tools that allow the user to specify the heritability model, and show that these tools enable substantially improved prediction of complex traits.

    • Qianqian Zhang
    • , Florian Privé
    •  & Doug Speed
  • Article
    | Open Access

    How the genetic background modifies the expression of mutations is a key question that is addressed in this study in the context of seam cell development in Caenorhabditis elegans isolates. One amino acid deletion in a conserved heat shock protein is sufficient to shape phenotype expressivity upon mutation of a GATA transcription factor.

    • Sneha L. Koneru
    • , Mark Hintze
    •  & Michalis Barkoulas
  • Article
    | Open Access

    Sex differences in fasting glucose and insulin have been identified, but the genetic loci underlying these differences have not. Here, the authors perform a meta-analysis of genome-wide association studies to detect sex-specific and sex-dimorphic loci associated with fasting glucose and insulin.

    • Vasiliki Lagou
    • , Reedik Mägi
    •  & Inga Prokopenko
  • Article
    | Open Access

    Huang et al. show that developing under different temperatures changes the genetic architecture of regulatory variation in Drosophila melanogaster gene expression yet the co-expression network remains robust. Data suggest that stabilizing selection on gene expression may promote co-expression network robustness.

    • Wen Huang
    • , Mary Anna Carbone
    •  & Trudy F. C. Mackay
  • Article
    | Open Access

    Here, the authors identify signatures of miRNA expression differentiation associated with Plasmodium falciparum infection and parasitemia in a longitudinal pediatric cohort in Burkina Faso. In particular, expression of several miRNAs known to promote lymphocyte cell death is affected during infection.

    • Mame Massar Dieng
    • , Aïssatou Diawara
    •  & Youssef Idaghdour
  • Article
    | Open Access

    In quantitative genetics, it is widely assumed that mutations combine additively or epistasis can be predicted with statistical or mechanistic models. Here, the authors use the phage lambda repressor model to show how biophysical ambiguity and non-monotonic functions confound phenotypic prediction.

    • Xianghua Li
    •  & Ben Lehner
  • Article
    | Open Access

    Genetic variation associated with gene expression changes has mostly been studied in the context of single nucleotide variants. Here, Jakubosky et al. report eQTL analysis of structural variants and short tandem repeats and find properties, such as length of variation, that affect the association.

    • David Jakubosky
    • , Matteo D’Antonio
    •  & Kelly A. Frazer
  • Article
    | Open Access

    Gene expression and how genetic variants can influence gene expression are tissue-specific processes with important implications for phenotypes. Here, Richardson et al. use eQTL data from GTEx and the eQTLGen project in a two-sample SMR + HEIDI framework for causal inference of gene expression associations with complex trait.

    • Tom G. Richardson
    • , Gibran Hemani
    •  & George Davey Smith
  • Article
    | Open Access

    DNA methylation is associated with complex traits and the expression of genes and proteins. Here, Zaghlool et al. perform epigenome-wide association studies for 1,123 plasma proteins, replicate obtained protein (p)QTMs in an independent cohort and find overlap of pQTMs with expression QTMs and previously reported disease associations.

    • Shaza B. Zaghlool
    • , Brigitte Kühnel
    •  & Karsten Suhre
  • Article
    | Open Access

    Rare genetic disorders (RGDs) often exhibit significant clinical variability among affected individuals. Here, Oetjens et al. systematically study the contribution of common genetic variation to variable expressivity of RGDs and find it is frequently influenced by polygenic factors identified in genome-wide association studies of relevant traits.

    • M. T. Oetjens
    • , M. A. Kelly
    •  & D. H. Ledbetter
  • Article
    | Open Access

    Aberrant morphology of the QRS complex in an electrocardiogram can be associated with cardiac morbidity and mortality. Here, the authors perform genome-wide association studies for ten measures of the QRS complex in 81,192 individuals and find 86 previously unreported loci that associate with at least one parameter.

    • Kristjan Norland
    • , Gardar Sveinbjornsson
    •  & Kari Stefansson
  • Article
    | Open Access

    Thousands of genetic loci are known to associate with human height, but these are mainly based on studies in European ancestry populations. Here, Akiyama et al. construct a genotype reference panel for the Japanese population followed by GWAS and report 573 height associated variants in 191,787 Japanese.

    • Masato Akiyama
    • , Kazuyoshi Ishigaki
    •  & Yoichiro Kamatani
  • Article
    | Open Access

    Many genetic variants identified in genome-wide association studies are associated with gene expression. Here, Porcu et al. propose a transcriptome-wide summary statistics-based Mendelian randomization approach (TWMR) that, applied to 43 human traits, uncovers hundreds of previously unreported gene–trait associations.

    • Eleonora Porcu
    • , Sina Rüeger
    •  & Zoltán Kutalik
  • Article
    | Open Access

    QTL mapping in multicellular animals usually requires generation, maintenance, and phenotyping large panels of recombinant individuals. Here, the authors develop ceX-QTL mapping, a method for fast genetic mapping via bulk selection on millions of unique recombinant C. elegans individuals.

    • Alejandro Burga
    • , Eyal Ben-David
    •  & Leonid Kruglyak
  • Article
    | Open Access

    Parent-of-origin effects (POE) are observed when there are different effects from alleles inherited from the two parents on phenotypic measures. Here, Zeng et al. study POE on DNA methylation in 5,101 individuals and identify genetic variants that associate with methylation variation via POE and their potential phenotypic consequences.

    • Yanni Zeng
    • , Carmen Amador
    •  & Chris S. Haley
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Review Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article |

    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