Featured
-
-
Article
| Open AccessCharacterizing rare and low-frequency height-associated variants in the Japanese population
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 AccessGenetic architecture of human plasma lipidome and its link to cardiovascular disease
Cardiovascular diseases (CVD) are associated with plasma lipid levels. Here, Tabassum et al. perform genome-wide association studies for lipidomic profiles with 141 (non-standard) lipid species which highlights shared genetic loci with CVD and that traditional lipids have low genetic correlation with other lipids.
- Rubina Tabassum
- , Joel T. Rämö
- & Samuli Ripatti
-
Article
| Open AccessThe transferability of lipid loci across African, Asian and European cohorts
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 AccessDiscovering genetic interactions bridging pathways in genome-wide association studies
Genetic interactions may contribute to phenotypic traits but are challenging to decipher. Here, the authors develop BridGE, a computational approach for identifying pathways connected by genetic interactions from GWAS data.
- Gang Fang
- , Wen Wang
- & Chad L. Myers
-
Article
| Open AccessGastroesophageal reflux GWAS identifies risk loci that also associate with subsequent severe esophageal diseases
Gastroesophageal reflux disease (GERD) is a major risk factor for Barret’s esophagus (BE) and esophageal adenocarcinoma (EA). Here, An et al. report 25 genetic loci for GERD, many of which associate with BE and EA or with other traits such as BMI.
- Jiyuan An
- , Puya Gharahkhani
- & Stuart MacGregor
-
Article
| Open AccessGenome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria
Urinary albumin-to-creatinine ratio (UCAR) is associated with various clinical outcomes such as kidney disease and cardiovascular disease. Here, the authors report genome-wide meta-analysis in over 500,000 individuals and find 68 UACR loci, followed by statistical fine-mapping, gene prioritization and experimental validation in flies.
- Alexander Teumer
- , Yong Li
- & Anna Köttgen
-
Article
| Open AccessGene-diet interactions associated with complex trait variation in an advanced intercross outbred mouse line
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 AccessFunctional disease architectures reveal unique biological role of transposable elements
Transposable elements (TE) make up a large component of the human genome and have been shown to contribute to human diseases. Here, Hormozdiari
et al . estimate the contribution of TEs to the heritability of 41 complex traits and diseases and find enrichment of SINEs in blood traits.- Farhad Hormozdiari
- , Bryce van de Geijn
- & Alkes L. Price
-
Article
| Open AccessComponents of genetic associations across 2,138 phenotypes in the UK Biobank highlight adipocyte biology
While many pleiotropic genetic loci have been identified, how they contribute to phenotypes across traits and diseases is unclear. Here, the authors propose decomposition of genetic associations (DeGAs), which uses singular value decomposition, to characterize the underlying latent structure of genetic associations of 2,138 phenotypes.
- Yosuke Tanigawa
- , Jiehan Li
- & Manuel A. Rivas
-
Article
| Open AccessVariants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration
Gestational duration depends on both maternal and fetal genetic influences. Here, the authors perform a fetal genome-wide association meta-analysis and find that a locus on 2q13 is associated with pregnancy duration and further show that the lead SNP rs7594852 changes the binding properties of transcriptional repressor HIC1.
- Xueping Liu
- , Dorte Helenius
- & Bjarke Feenstra
-
Article
| Open AccessGSNOR provides plant tolerance to iron toxicity via preventing iron-dependent nitrosative and oxidative cytotoxicity
How plants deal with iron toxicity is still unclear. Here, the authors reveal that S-nitrosoglutathione-reductase (GSNOR) provides tolerance to iron toxicity by preventing iron-dependent nitrosative and oxidative cytotoxicity in Arabidopsis, legumes, and rice.
- Baohai Li
- , Li Sun
- & Wolfgang Busch
-
Article
| Open AccessIntegrative transcriptome imputation reveals tissue-specific and shared biological mechanisms mediating susceptibility to complex traits
PrediXcan is a widely used gene expression imputation method that links genetic variants to gene expression. Here, the authors develop EpiXcan which leverages epigenetic annotations to inform transcriptomic imputation and further use the obtained gene-trait associations for computational drug repurposing.
- Wen Zhang
- , Georgios Voloudakis
- & Panos Roussos
-
Article
| Open AccessEarly progression to active tuberculosis is a highly heritable trait driven by 3q23 in Peruvians
Between 5 and 15% of latent Mycobacterium tuberculosis infections develop into active tuberculosis (TB). Here, Luo et al. report a genome-wide association study for early TB progression in a total of 4002 active TB cases and their household contacts in Peru and they identify a locus on 3q23 in which ATP1B3 is mapped as the likely causal gene.
- Yang Luo
- , Sara Suliman
- & Soumya Raychaudhuri
-
Article
| Open AccessGenome-wide association study identifies 14 previously unreported susceptibility loci for adolescent idiopathic scoliosis in Japanese
Adolescent idiopathic scoliosis (AIS) is a common pediatric disease leading to spinal deformities. Here, the authors report GWAS followed by genome-wide meta-analysis in up to 79,211 Japanese individuals, identifying 20 genetic loci for AIS, 14 of which were previously unreported, and perform in vitro validation for rs1978060.
- Ikuyo Kou
- , Nao Otomo
- & Shiro Ikegawa
-
Article
| Open AccessA meta-analysis of genome-wide association studies identifies multiple longevity genes
Genome-wide association studies have only revealed a handful of genetic loci for longevity. Here, in a case–control design based on phenotype definitions of individuals surviving at or beyond the age corresponding to the 90th and 99th survival percentile, the authors report two additional loci located in the APOE locus and near GPR78.
- Joris Deelen
- , Daniel S. Evans
- & Joanne M. Murabito
-
Article
| Open AccessGWAS for urinary sodium and potassium excretion highlights pathways shared with cardiovascular traits
Levels of sodium and potassium in urine are associated with cardiovascular traits. Here, Pazoki et al. perform genome-wide association studies for urinary sodium and potassium secretion and identify 50 and 13 novel loci, respectively, some of which show a potential causal relationship with blood pressure based on MR analysis.
- Raha Pazoki
- , Evangelos Evangelou
- & Abbas Dehghan
-
Article
| Open AccessGenome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes
A main symptom of chronic insufficient sleep is excessive daytime sleepiness. Here, Wang et al. report 42 genome-wide significant loci for self-reported daytime sleepiness in 452,071 individuals from the UK Biobank that cluster into two biological subtypes of either sleep propensity or sleep fragmentation.
- Heming Wang
- , Jacqueline M. Lane
- & Richa Saxena
-
Article
| Open AccessInsight into genetic predisposition to chronic lymphocytic leukemia from integrative epigenomics
The definition of regulatory landscape at chronic lymphocytic leukaemia (CLL) risk loci is limited. Here, the authors perform an epigenomic characterisation of 42 known risk loci in CLL and normal B cells at different developmental stages and show active chromatin and target genes in the risk loci.
- Helen E. Speedy
- , Renée Beekman
- & José I. Martín-Subero
-
Article
| Open AccessCytokinin functions as an asymmetric and anti-gravitropic signal in lateral roots
Lateral roots emerge from the primary root at right angles but briefly grow asymmetrically to set a distinct growth angle. Here Waidmann et al. show that cytokinin acts as an anti-gravitropic signal that impairs growth on the upper side of emerged lateral roots to promote radial expansion of the root system.
- Sascha Waidmann
- , Michel Ruiz Rosquete
- & Jürgen Kleine-Vehn
-
Article
| Open AccessA machine-compiled database of genome-wide association studies
Most databases of genotype-phenotype associations are manually curated. Here, Kuleshov et al. describe a machine curation system that extracts such relationships from the GWAS literature and synthesizes them into a structured knowledge base called GWASkb that can complement manually curated databases.
- Volodymyr Kuleshov
- , Jialin Ding
- & Michael Snyder
-
Article
| Open AccessNon-coding variability at the APOE locus contributes to the Alzheimer’s risk
Several studies show that APOE-ε4 coding variants are associated with Alzheimer’s disease (AD) risk. Here, Zhou et al. perform fine-mapping of the APOE region and find AD risk haplotypes with non-coding variants in the PVRL2 and APOC1 regions that are associated with relevant endophenotypes.
- Xiaopu Zhou
- , Yu Chen
- & Nancy Y. Ip
-
Article
| Open AccessAnalysis of polygenic risk score usage and performance in diverse human populations
Predominant participation of European-ancestry individuals in genetic studies has hindered the better understanding of genetic risk in non-European ancestry individuals. Here, Duncan et al. quantify polygenic risk score use and performance in worldwide populations.
- L. Duncan
- , H. Shen
- & B. Domingue
-
Article
| Open AccessStochastic search and joint fine-mapping increases accuracy and identifies previously unreported associations in immune-mediated diseases
Statistical fine-mapping to pinpoint likely causal variants in a genomic region is complicated by linkage disequilibrium (LD). Here, Asimit et al. compare stepwise and stochastic approaches to fine-mapping and propose a Bayesian multinomial stochastic search method which they apply to six immune-mediated diseases.
- Jennifer L. Asimit
- , Daniel B. Rainbow
- & Chris Wallace
-
Article
| Open AccessZRANB3 is an African-specific type 2 diabetes locus associated with beta-cell mass and insulin response
Type 2 diabetes (T2D) is prevalent in populations worldwide, however, mostly studied in European and mixed-ancestry populations. Here, the authors perform a genome-wide association study for T2D in over 5,000 sub-Saharan Africans and identify a locus, ZRANB3, that is specific for this population.
- Adebowale A. Adeyemo
- , Norann A. Zaghloul
- & Charles N. Rotimi
-
Article
| Open AccessGenetic mapping of cell type specificity for complex traits
Tissue- and cell type-specific information helps to interpret findings from genome-wide association studies. Here, the authors leverage multiple single cell expression datasets to infer cell type specificity of traits.
- Kyoko Watanabe
- , Maša Umićević Mirkov
- & Danielle Posthuma
-
Article
| Open AccessGenome and epigenome wide studies of neurological protein biomarkers in the Lothian Birth Cohort 1936
Plasma levels of neurological proteins have the potential to serve as biomarkers for neurological conditions. Here, Hillary et al. perform genome- and epigenome-wide association studies for 92 neurological proteins and identify 41 genomic loci for 33 proteins and 26 CpG sites for 9 proteins.
- Robert F. Hillary
- , Daniel L. McCartney
- & Riccardo E. Marioni
-
Article
| Open AccessMendelian randomisation analysis of the effect of educational attainment and cognitive ability on smoking behaviour
Higher educational attainment is positively associated with a number of health outcomes. Here, Sanderson et al. use multivariable Mendelian randomisation analysis to test whether the association of educational attainment with smoking behaviour is direct or indirectly mediated via general cognitive ability.
- Eleanor Sanderson
- , George Davey Smith
- & Marcus R. Munafò
-
Article
| Open AccessGenome-wide analysis of dental caries and periodontitis combining clinical and self-reported data
Dental caries and periodontitis are among the most common medical conditions. Here, the authors report a GWAS for measures of oral health that reveals 47 risk loci for caries, find genetic correlation with 31 other complex traits and use Mendelian randomization analyses to explore potential causal relationships.
- Dmitry Shungin
- , Simon Haworth
- & Ingegerd Johansson
-
Article
| Open AccessVariation of a major facilitator superfamily gene contributes to differential cadmium accumulation between rice subspecies
Grain of indica rice accumulates more toxic cadmium (Cd) than japonica, but the underlying genetic basis is unclear. Here, the authors show that natural variation of OsCd1 contributes to divergence in grain Cd accumulation and transferring japonica allele to indica rice leads to reduced Cd accumulation.
- Huili Yan
- , Wenxiu Xu
- & Zhenyan He
-
Article
| Open AccessFacial recognition from DNA using face-to-DNA classifiers
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 AccessLoci for human leukocyte telomere length in the Singaporean Chinese population and trans-ethnic genetic studies
Shortening of leukocyte telomere length (LTL) is associated with age and increased risk for various chronic diseases. Here, the authors report genome-wide association studies for LTL in Singaporean Chinese populations and find that longer LTL associates with less severe outcomes of respiratory disease phenotypes.
- Rajkumar Dorajoo
- , Xuling Chang
- & Chew-Kiat Heng
-
Article
| Open AccessBivariate causal mixture model quantifies polygenic overlap between complex traits beyond genetic correlation
To better understand the phenotypic relationships of complex traits it is also important to understand their genetic overlap. Here, Frei et al. develop MiXeR which uses GWAS summary statistics to evaluate the polygenic overlap between two traits irrespective of their genetic correlation.
- Oleksandr Frei
- , Dominic Holland
- & Anders M. Dale
-
Article
| Open AccessA systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis
Genome-wide association studies (GWAS) have so far uncovered more than 200 loci for multiple sclerosis (MS). Here, the authors integrate data from various sources for a cell type-specific pathway analysis of MS GWAS results that specifically highlights the involvement of the immune system in disease pathogenesis.
- Lohith Madireddy
- , Nikolaos A. Patsopoulos
- & Sergio E. Baranzini
-
Article
| Open AccessJoint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis
Streptococcus pneumoniae is a causative agent of meningitis and bacteremia. In a combined pathogen and host GWAS, Lees et al. find that host genetic variation is associated with both susceptibility and severity of pneumococcal meningitis, and specific bacterial genetic variation associated with susceptibility.
- John A. Lees
- , Bart Ferwerda
- & Diederik van de Beek
-
Article
| Open AccessAssociation analyses identify 31 new risk loci for colorectal cancer susceptibility
In colorectal cancer (CRC), finding loci associated with risk may give insight into disease aetiology. Here, the authors report a genome-wide association analysis in Europeans of 34,627 CRC cases and 71,379 controls, and find 31 new risk loci and 17 new risk SNPs at previously reported loci.
- Philip J. Law
- , Maria Timofeeva
- & Malcolm G. Dunlop
-
Article
| Open AccessGWAS for quantitative resistance phenotypes in Mycobacterium tuberculosis reveals resistance genes and regulatory regions
Resistance to antibiotics hampers the treatment of infectious diseases such as tuberculosis (TB). Here, Farhat et al. perform genome-wide association testing for minimum inhibitory concentration (MIC) of 12 anti-TB drugs in whole-genome sequenced clinical M. tuberculosis isolates and identify 13 genomic loci.
- Maha R. Farhat
- , Luca Freschi
- & Megan Murray
-
Article
| Open AccessGWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures
Size and shape of bones are important for height and body shape. Here, Styrkarsdottir et al identify 12 loci in a GWAS for bone area derived from DXA scans and show that these loci associate with other bone-related phenotypes including osteoarthritis, height, bone mineral density and risk of hip fracture.
- Unnur Styrkarsdottir
- , Olafur A. Stefansson
- & Kari Stefansson
-
Article
| Open AccessSex-specific and pleiotropic effects underlying kidney function identified from GWAS meta-analysis
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 AccessGenome-wide association study of medication-use and associated disease in the UK Biobank
An understanding of the genetic variants associated with medication use may shed light on the underlying biological pathways of disease, and aid in drug development. Here, Wu and colleagues conduct a GWAS for self-reported medication-use in the UK Biobank, finding more than 500 independent variants and many promising leads for future work.
- Yeda Wu
- , Enda M. Byrne
- & Naomi R. Wray
-
Article
| Open AccessPolygenic prediction via Bayesian regression and continuous shrinkage priors
Polygenic risk scores (PRS) have the potential to predict complex diseases and traits from genetic data. Here, Ge et al. develop PRS-CS which uses a Bayesian regression framework, continuous shrinkage (CS) priors and an external LD reference panel for polygenic prediction of binary and quantitative traits from GWAS summary statistics.
- Tian Ge
- , Chia-Yen Chen
- & Jordan W. Smoller
-
Article
| Open AccessA PRPH splice-donor variant associates with reduced sural nerve amplitude and risk of peripheral neuropathy
Diagnosis and classification of peripheral neuropathy (PN) is facilitated by nerve conduction (NC) studies. Here, Bjornsdottir et al. find a low-frequency PRPH splice-donor variant that associates with NC amplitude and neurological assessment of recalled PRPH variant carriers reveals increased risk of a mild sensory-negative PN.
- Gyda Bjornsdottir
- , Erna V. Ivarsdottir
- & Kari Stefansson
-
Article
| Open AccessGenetic studies of accelerometer-based sleep measures yield new insights into human sleep behaviour
Quality, quantity and timing of sleep are important factors for overall human health. Here, the authors perform GWAS for sleep traits estimated using wearable accelerometers and identify 47 genetic associations, including 26 novel associations for measures of sleep quality and 10 for nocturnal sleep duration.
- Samuel E. Jones
- , Vincent T. van Hees
- & Andrew R. Wood
-
Article
| Open AccessAdjustment for index event bias in genome-wide association studies of subsequent events
Different from GWAS for susceptibility to disease, GWAS for prognosis or survival may be vulnerable to selection bias. Here, Dudbridge et al present an approach to reduce index event bias in simulated and realistic situations, and apply it to GWAS of survival with idiopathic pulmonary fibrosis and Crohn’s disease prognosis.
- Frank Dudbridge
- , Richard J. Allen
- & Riyaz S. Patel
-
Article
| Open AccessMeta-analysis of genome-wide association studies provides insights into genetic control of tomato flavor
Flavor is one of the most important traits for improving tomato sensory quality and consumer acceptability. Here, the authors report meta-analysis of genome-wide association studies of flavor related traits and show genetic insights into the influence of human selection during domestication and improvement.
- Jiantao Zhao
- , Christopher Sauvage
- & Mathilde Causse
-
Article
| Open AccessWhole genome sequencing of canids reveals genomic regions under selection and variants influencing morphology
Being man’s best friend, dogs have been bred and selected for certain morphologic traits and breed-associated behaviours. Here, Plassais et al. analyse 722 canine whole genome sequences including modern breeds, wild canids and village dogs by GWAS and search for signatures of selection.
- Jocelyn Plassais
- , Jaemin Kim
- & Elaine A. Ostrander
-
Article
| Open AccessGenome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations
The genetic underpinnings of alcohol use disorder and consumption are incompletely understood. Here, the authors perform GWAS for Alcohol Use Disorder (AUD) Identification Test-Consumption scores and AUD diagnosis from electronic health records of 274,424 individuals and identify a total of 18 associated loci.
- Henry R. Kranzler
- , Hang Zhou
- & Joel Gelernter
-
Article
| Open AccessParent of origin genetic effects on methylation in humans are common and influence complex trait variation
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 AccessSequence variation at ANAPC1 accounts for 24% of the variability in corneal endothelial cell density
The corneal endothelium is crucial for proper vision. Here, Ivarsdottir et al. perform genome-wide association studies for various corneal endothelial cell measurements and find that an intergenic variant near ANAPC1 explains 24% of the variance of endothelial cell density and associates with corneal hysteresis.
- Erna V. Ivarsdottir
- , Stefania Benonisdottir
- & Kari Stefansson
-
Article
| Open AccessWhole-genome resequencing reveals Brassica napus origin and genetic loci involved in its improvement
Brassica napus is a globally important oil crop, but the origin of the allotetraploid genome and its improvement process are largely unknown. Here, the authors take a population genetic approach to resolve its origin and evolutionary history, and identify candidate genes related to important agricultural traits.
- Kun Lu
- , Lijuan Wei
- & Jiana Li