Heritable quantitative trait

  • Article
    | Open Access

    We lack a comprehensive understanding of how Neanderthal ancestry influences human traits. This study finds that regions with Neanderthal ancestry are broadly depleted of trait-associated variation; yet, introgressed variants likely contributed to human adaptation in a few traits, like skin color and immune response modulation.

    • Evonne McArthur
    • , David C. Rinker
    •  & John A. Capra
  • 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

    Platelet aggregation is associated with myocardial infarction and stroke. Here, the authors have conducted a whole genome sequencing association study on platelet aggregation, discovering a locus in RGS18, where enhancer assays suggest an effect on activity of haematopoeitic lineage transcription factors.

    • Ali R. Keramati
    • , Ming-Huei Chen
    •  & Andrew D. Johnson
  • Article
    | Open Access

    Accurately measuring genetic relatedness by Identical-By-Descent (IBD) segments is challenging in biobank-level genome data. The authors present IBD method FastSMC, which when applied to the UK Biobank gives a detailed picture of genetic relatedness and evolutionary history in the UK over the past 2000 years.

    • Juba Nait Saada
    • , Georgios Kalantzis
    •  & Pier Francesco Palamara
  • Article
    | Open Access

    Enhancer RNAs are transcribed bidirectionally from core transcription initiation regions. Here, by employing nascent RNA sequencing, the authors identify quantitative trait loci (QTLs) associated with enhancer RNA level and directionality, revealing the bipartite architecture of enhancers.

    • Katla Kristjánsdóttir
    • , Alexis Dziubek
    •  & Hojoong Kwak
  • Article
    | Open Access

    Variance components analysis may be used for a variety of applications including heritability estimation and association mapping. Here, the authors present a computationally efficient method, scalable to extremely large GWAS datasets, and use it for heritabilty analysis of 22 traits from UK Biobank

    • Ali Pazokitoroudi
    • , Yue Wu
    •  & Sriram Sankararaman
  • Article
    | Open Access

    Ageing phenotypes are of great interest but are difficult to study genetically, partly due to the sample sizes required. Here, the authors present a multivariate framework to combine GWAS summary statistics and increase statistical power, identifying additional loci enriched for aging.

    • Paul R. H. J. Timmers
    • , James F. Wilson
    •  & Joris Deelen
  • 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

    Studying the genetic effects on early stages of human development is challenging due to a scarcity of biological material. Here, the authors utilise induced pluripotent stem cells from 125 donors to track gene expression changes and expression quantitative trait loci at single cell resolution during in vitro endoderm differentiation.

    • Anna S. E. Cuomo
    • , Daniel D. Seaton
    •  & Oliver Stegle
  • Article
    | Open Access

    Blood metabolite levels are under the influence of environmental and genetic factors. Here, Hagenbeek et al. perform heritability estimations for metabolite measures and determine the contribution of known metabolite loci to metabolite levels using data from 40 genome-wide association studies.

    • Fiona A. Hagenbeek
    • , René Pool
    •  & Dorret I. Boomsma
  • 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

    The majority of published GWAS was performed in European ancestry populations. Here, Kuchenbaecker et al., test to which extent lipid loci are shared and find that the major lipid loci are mostly transferrable between Europeans and Asians while there are notable exceptions for African populations.

    • Karoline Kuchenbaecker
    • , Nikita Telkar
    •  & Dieter Wolke
  • Article
    | Open Access

    Complex traits associate with genetic variation and environment and their interaction. Here, the authors study the influence of different diets on trait variability in 1154 outbred mice from an advanced intercross line and find gene-diet interactions associated with spontaneous autoimmunity development in these animals.

    • Artem Vorobyev
    • , Yask Gupta
    •  & Ralf J. Ludwig
  • Article
    | Open Access

    Functional variants have been proposed to alter transcription factor binding. Here, the authors provide direct evidence that functional variants within the TBC1D4 gene, encoding an NFκB binding site, can alter transcription factor binding, and use CRISPR-Cas9 to reveal localization of the transcription factor to be the regulator of chromatin accessibility and p65 binding and ultimately TBC1D4 expression.

    • Andrew D. Johnston
    • , Claudia A. Simões-Pires
    •  & John M. Greally
  • Article
    | Open Access

    Dosage compensation (DC) on the X chromosome has predictable effects on genetic and phenotypic trait variance. Here, the authors use information for 20 quantitative traits in the UK Biobank and across-tissue gene expression to compare X-linked heritability and the effects of trait-associated SNPs between the sexes.

    • Julia Sidorenko
    • , Irfahan Kassam
    •  & Peter M. Visscher
  • Article
    | Open Access

    Prediction of face from DNA followed by matching to facial images has been proposed for forensic applications. Here, Sero et al. present a different approach that can establish facial identity from DNA without directly predicting the face but is based on classifying given faces by individual DNA-encoded traits.

    • Dzemila Sero
    • , Arslan Zaidi
    •  & Peter Claes
  • Article
    | Open Access

    Estimated glomerular filtration rate (eGFR) is a measure of kidney function and used to characterize chronic kidney disease. Here, Graham et al. identify 53 novel loci for eGFR in a GWAS meta-analysis, a subset of which are associated with other common diseases, such as diabetes and hypertension, based on PheWAS.

    • Sarah E. Graham
    • , Jonas B. Nielsen
    •  & Cristen J. Willer
  • Article
    | Open Access

    While human lifespan is only moderately heritable, “getting old” runs in families. Here, van den Berg et al. study mortality data from three-generation cohorts to define a threshold for longevity and find that individuals have an increasing survival advantage with each additional relative in the top 10% survivors of their birth cohort.

    • Niels van den Berg
    • , Mar Rodríguez-Girondo
    •  & P. Eline Slagboom
  • Article
    | Open Access

    Male pattern baldness (MPB) is a polygenic trait that affects the majority of European men. Here, Yap et al. estimate heritability, partitioned by autosomes and the X-chromosome, of MPB in the UK Biobank cohort, perform GWAS for MPB and find genetic correlation with other sex-specific traits.

    • Chloe X. Yap
    • , Julia Sidorenko
    •  & Peter M. Visscher
  • Article
    | Open Access

    Latin Americans trace their ancestry to the admixture of Native Americans, Europeans and Sub-Saharan Africans. Here, the authors develop a novel haplotype-based approach and analyse over 6,500 Latin Americans to infer the geographically-detailed genetic structure of this population.

    • Juan-Camilo Chacón-Duque
    • , Kaustubh Adhikari
    •  & Andrés Ruiz-Linares
  • 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

    Carotid intima-media thickness (cIMT) and plaque are associated with subclinical atherosclerosis and coronary heart disease (CHD). Here, the authors identify and prioritize genetic loci for cIMT and plaque by GWAS and colocalization approaches and further demonstrate genetic correlation with CHD and stroke.

    • Nora Franceschini
    • , Claudia Giambartolomei
    •  & Christopher J. O’Donnell
  • Article
    | Open Access

    An increase in the volume of the brain lateral ventricles is a sign of normal aging, but can also be associated with neurological and psychiatric disorders. Here, Vojinovic et al. identify seven genetic loci in a GWA study for ventricular volume in 23,500 individuals and find correlation with thalamus volume.

    • Dina Vojinovic
    • , Hieab H. Adams
    •  & Myriam Fornage
  • Article
    | Open Access

    Disease risk variants can exert their influence on phenotypes by altering epigenome function. Here, Pelikan et al. show that variants inducing allelic imbalance in histone marks in lymphoblastoid cell lines from lupus patients are enriched in autoimmune disease haplotypes and influence gene expression.

    • Richard C. Pelikan
    • , Jennifer A. Kelly
    •  & Patrick M. Gaffney
  • Article
    | Open Access

    Hand grip strength as a proxy of muscular fitness is a clinical predictor of mortality and morbidity. In a large-scale GWA study, the authors find 16 robustly associated genetic loci that highlight roles in muscle fibre structure and function, neuronal maintenance and nervous system signal transduction.

    • Sara M. Willems
    • , Daniel J. Wright
    •  & Robert A. Scott
  • Article
    | Open Access

    Neuroanatomical shape measurements are multidimensional geometric descriptions of brain structure. This study develops multivariate heritability analysis methods and examines structural brain MRI scans and genetic data to estimate the heritability of neuroanatomical shape.

    • Tian Ge
    • , Martin Reuter
    •  & Mert R. Sabuncu
  • Article
    | Open Access

    Physiological effects of psychological stress and infection in mothers can increase the incidence of anxiety and psychiatric diseases in offsprings and in subsequent generation. Here, Miklos Toth and colleagues show that intergenerational inheritance of neurological traits is propagated across multiple generations independently by parallel non-genetic mechanisms involving independent segregation of epigenetic specific loci.

    • Emma Mitchell
    • , Shifra L. Klein
    •  & Miklos Toth
  • Article
    | Open Access

    Heritability of complex traits can be finely dissected using yeast crosses. Here, Kaspar Märtens and colleagues show that quantitative traits in yeast can be predicted from genotype and phenotype data with an average coefficient of determination of 0.91, providing the most accurate predictions of complex traits to date.

    • Kaspar Märtens
    • , Johan Hallin
    •  & Leopold Parts
  • Article
    | Open Access

    Panicle architecture is an important determinant of crop yield and a target of selection by plant breeders. Here, Crowell et al.combine image-based phenotyping with high-density array-based genotyping to perform a genome-wide association study revealing a number of candidate genes linked to panicle variation in rice.

    • Samuel Crowell
    • , Pavel Korniliev
    •  & Susan McCouch
  • Article
    | Open Access

    This study uses a large number of crosses between a common lab strain and vineyard-isolated strain of yeast, and estimates the phenotypic variance for various quantitative traits. Using this data set, the authors show additive quantitative trait loci (QTL) and QTL–QTL interactions to be on average 43% and 9%, respectively.

    • Joshua S. Bloom
    • , Iulia Kotenko
    •  & Leonid Kruglyak
  • Article
    | Open Access

    Genome-wide association studies have identified regions which confer risk of high-grade serous epithelial ovarian cancer. Here the authors use expression quantitative train locus analysis to identify candidate genes and functionally characterise them, identifying a role for HOXD9 in ovarian cancer.

    • Kate Lawrenson
    • , Qiyuan Li
    •  & Matthew L. Freedman
  • Article
    | Open Access

    Adenosine-to-inosine (A-to-I) RNA editing plays an important role in neurological functions. Here, by a quantitative trait loci (QTL) mapping approach in 131 Drosophila melanogasterstrains, the authors identify 545 QTLs associated with differences in RNA editing.

    • Gokul Ramaswami
    • , Patricia Deng
    •  & Jin Billy Li
  • Article
    | Open Access

    Neutrophils are abundant immune cells important for antimicrobial defence and in autoimmunity. Here, by mapping expression quantitative trait loci (eQTL) in neutrophils of Chinese ethnicity from Singapore, Andiappan et al.provide a resource for understanding immune-related trait associated genetic variants.

    • Anand Kumar Andiappan
    • , Rossella Melchiotti
    •  & Olaf Rotzschke
  • Article
    | Open Access

    Neutrophils are the most abundant subset of leukocyte and central to many diseases. Here by mapping expression quantitative trait loci (eQTL) in the context of epigenetic marks in neutrophils and monocytes of 101 healthy European adults, the authors provide a resource to advance understanding of immune-related trait-associated genetic variants.

    • Vivek Naranbhai
    • , Benjamin P. Fairfax
    •  & Julian C. Knight
  • Article |

    As important post-transcriptional regulators of gene expression, microRNAs play a key role in the generation of complex phenotypes. Here, Huan et al.identify miR-eQTLs in whole blood samples to create a roadmap linking regulation of microRNA expression to complex diseases.

    • Tianxiao Huan
    • , Jian Rong
    •  & Jane E. Freedman