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| Open AccessA genome-wide association study identifies six novel risk loci for primary biliary cholangitis
Primary biliary cholangitis is an autoimmune liver disease. Here, the authors show that variants in interleukin genes which potentially deregulate their expression are associated with this condition, and suggest that the IL21 signalling pathway may have a role in disease aetiology.
- Fang Qiu
- , Ruqi Tang
- & Xiong Ma
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Article
| Open AccessGenome-wide association study identifies three novel loci in Fuchs endothelial corneal dystrophy
Fuchs endothelial corneal dystrophy (FECD) is one of the most common reasons for corneal transplantation, and is known to cluster in families. Here, the authors discover new genetic loci associated with FECD with sex-specific effects and implications for disease mechanism.
- Natalie A. Afshari
- , Robert P. Igo Jr
- & Sudha K. Iyengar
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Article
| Open AccessIdentification of common non-coding variants at 1p22 that are functional for non-syndromic orofacial clefting
Many genetic variants have been associated with complex congenital disorders, but their function is not always clear. Here, the authors develop a pipeline to functionally characterize such variants, and show potential roles for three SNPs in non-syndromic cleft lip and palate.
- Huan Liu
- , Elizabeth J. Leslie
- & Robert A. Cornell
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Article
| Open AccessMeta-analysis identifies novel risk loci and yields systematic insights into the biology of male-pattern baldness
Male-pattern baldness is a common condition in which hair is progressively lost from the scalp. Here, the authors find 23 new genetic variants associated with this condition and suggest that it is not an isolated trait but may share an underlying biological basis with various diseases.
- Stefanie Heilmann-Heimbach
- , Christine Herold
- & Markus M. Nöthen
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Article
| Open AccessConnecting genetic risk to disease end points through the human blood plasma proteome
Individual genetic variation can affect the levels of protein in blood, but detailed data sets linking these two types of data are rare. Here, the authors carry out a genome-wide association study of levels of over a thousand different proteins, and describe many new SNP-protein interactions.
- Karsten Suhre
- , Matthias Arnold
- & Johannes Graumann
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| Open AccessSequence variant at 8q24.21 associates with sciatica caused by lumbar disc herniation
Lumbar disc herniation (LDH) can cause persistent sciatica, and in some cases surgery is required to relieve symptoms. Here, the authors carry out a genome-wide association study using microdiscectomy as an indicator of severe LDH, and find a locus on chromosome 8 associated with this condition.
- Gyda Bjornsdottir
- , Stefania Benonisdottir
- & Kari Stefansson
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Article
| Open AccessA genome-wide association study yields five novel thyroid cancer risk loci
Non-medullary thyroid cancers include papillary and follicular subtypes, and are the most common type of thyroid cancer. Here, the authors extend previous work by performing a large genome-wide association study and find five novel loci associated with this disease.
- Julius Gudmundsson
- , Gudmar Thorleifsson
- & Kari Stefansson
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Article
| Open AccessGenome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia
Chronic lymphocytic leukaemia has a hereditary component, much of which remains to be identified. Here, the authors perform a genome-wide association study and find new risk loci for the disease, which are associated with genes involved in immune function.
- Philip J. Law
- , Sonja I. Berndt
- & Susan Slager
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Article
| Open AccessGenome-wide association study of prostate-specific antigen levels identifies novel loci independent of prostate cancer
Prostate-specific antigen is used as a biomarker of prostate cancer, but levels can be affected by other factors not related to cancer. Here, the authors find genes associated with prostate specific antigen levels in healthy men, which could be used to reduce over-diagnosis and over-treatment.
- Thomas J. Hoffmann
- , Michael N. Passarelli
- & John S. Witte
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Article
| Open AccessNovel genetic loci associated with hippocampal volume
The hippocampus in mammalian brain varies in size across individuals. Here, Hibar and colleagues perform a genome-wide association meta-analysis to find six genetic loci with significant association to hippocampus volume.
- Derrek P. Hibar
- , Hieab H. H. Adams
- & M. Arfan Ikram
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Article
| Open AccessA large-scale genome-wide association and meta-analysis identified four novel susceptibility loci for leprosy
Previous studies have shown genetic associations between leprosy and 18 different genes/loci. Here, Wang and colleagues perform genome-wide association study in Han Chinese leprosy patients and describe four novel loci to be associated to the disease.
- Zhenzhen Wang
- , Yonghu Sun
- & Furen Zhang
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Article
| Open AccessMultiple myeloma risk variant at 7p15.3 creates an IRF4-binding site and interferes with CDCA7L expression
Genome wide association studies have identified multiple risk loci for multiple myeloma. Here, the authors show that the expression of CDCA7Lis associated with patient survival and expression of the gene is influenced by a risk variant at 7p15.3, which creates a transcription factor binding site for IRF4.
- Ni Li
- , David C. Johnson
- & Richard S. Houlston
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Article
| Open AccessA principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
Past genome-wide associate studies have identified hundreds of genetic loci that influence body size and shape when examined one trait at a time. Here, Jeff and colleagues develop an aggregate score of various body traits, and use meta-analysis to find new loci linked to body shape.
- Janina S. Ried
- , Janina Jeff M.
- & Ruth J. F. Loos
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Article
| Open AccessSalinity tolerance loci revealed in rice using high-throughput non-invasive phenotyping
Image-based plant phenotyping can be used to collect data with high temporal and spatial resolution. Here, the authors develop a computationally efficient method using smoothing splines and a new marker-by-trait association model to identify loci in a diverse rice population associated with early response to salinity.
- Nadia Al-Tamimi
- , Chris Brien
- & Sónia Negrão
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Article
| Open AccessEpigenetic and genetic components of height regulation
Adult height has a strong genetic component and is highly heritable. Here the authors whole-genome sequence 8,453 Icelanders and find novel parent-of-origin derived associations in IGF2-H19 and DLK1-MEG3.
- Stefania Benonisdottir
- , Asmundur Oddsson
- & Kari Stefansson
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| Open AccessA multi-marker association method for genome-wide association studies without the need for population structure correction
Currently available methods for phenotype to genetic markers association need to account for population structure. Here, Klasen et al. devise a statistical method called Quantitative Trait Cluster Association Test (QTCAT) that overcomes the need for population structure correction.
- Jonas R. Klasen
- , Elke Barbez
- & Korbinian Schneeberger
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Article
| Open AccessGenome-wide association study of 12 agronomic traits in peach
Peach is both an economically important crop species and a model for Rosaceae fruit development research. Here, the authors perform genome-wide association analysis in peach and find candidate genes associated with variation in agronomically important fruit phenotypes.
- Ke Cao
- , Zhengkui Zhou
- & Lirong Wang
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| Open AccessComparative and parallel genome-wide association studies for metabolic and agronomic traits in cereals
The plant metabolome is often considered as a bridge between genomic and phenotypic variation. Here, the authors perform metabolic and phenotypic genome-wide association studies in rice grain, and compare to prior studies on rice leaf and maize kernel, to demonstrate a new strategy to investigate complex traits.
- Wei Chen
- , Wensheng Wang
- & Jie Luo
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Article
| Open AccessGenome-wide association study for acute otitis media in children identifies FNDC1 as disease contributing gene
Acute otitis media (AOM) is an acute infection of middle ear mucosa and among the most common pediatric diseases. Here, the authors performed a genome-wide association study to link a variant in the FNDC1 locus on 6q25.3 and differential methylation status of the FNDC1gene with predisposition to AOM.
- Gijs van Ingen
- , Jin Li
- & Hakon Hakonarson
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Article
| Open AccessSequence element enrichment analysis to determine the genetic basis of bacterial phenotypes
Plasticity and clonal population structure in bacterial genomes can hinder traditional SNP-based genetic association studies. Here, Corander and colleagues present a method to identify variable-length sequence elements enriched in a phenotype of interest, and demonstrate its use in human pathogens.
- John A. Lees
- , Minna Vehkala
- & Jukka Corander
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| Open AccessProteome-wide association studies identify biochemical modules associated with a wing-size phenotype in Drosophila melanogaster
How genetic diversity generates complex phenotypes along a continuum remains a fundamental question of biology. Here—applying the emerging SWATH proteomics technology—the authors describe a proteome wide association study (PWAS) of Drosophila wing size and identify functional protein clusters associated with this trait.
- Hirokazu Okada
- , H. Alexander Ebhardt
- & Ernst Hafen
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Article
| Open AccessA protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis
While hundreds of loci are linked with inflammatory bowel diseases (IBDs), the functional consequences of the associated variants remain unclear. Here, the authors screened in ulcerative colitis (UC) patients’ genomes for protein-truncating variants near IBD loci, and identify a protein truncating variant in RNF186to be protective against UC.
- Manuel A. Rivas
- , Daniel Graham
- & Mark J. Daly
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Article
| Open AccessCommon variants upstream of KDR encoding VEGFR2 and in TTC39B associate with endometriosis
Endometriosis is a common gynaecological disease but the underlying pathogenesis is poorly understood, however there is a strong familial component. Here the authors conduct a genome wide association study and identify a novel susceptibility locus that correlates with disease severity.
- Valgerdur Steinthorsdottir
- , Gudmar Thorleifsson
- & Kari Stefansson
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Article
| Open AccessGenome-wide association study identifies novel susceptibility loci for cutaneous squamous cell carcinoma
Cutaneous squamous cell carcinoma is the second most common type of skin cancer. In this genome-wide association study, which includes over 7,000 cases, the authors identify 4 new susceptibility loci for this cancer and also provide independent replication of 9 previously reported susceptibility loci.
- Harvind S. Chahal
- , Yuan Lin
- & Kavita Y. Sarin
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Article
| Open AccessGenome-wide association study identifies multiple susceptibility loci for multiple myeloma
Previous genome-wide association studies have identified loci associated with the risk of multiple myeloma. Here, the authors present a meta-analysis of six genome wide association studies of the disease and identify eight new loci; functional studies identify genes as candidates for the basis of these associations.
- Jonathan S. Mitchell
- , Ni Li
- & Richard S. Houlston
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Article
| Open AccessProsaposin is a regulator of progranulin levels and oligomerization
Increasing progranulin (PGRN) levels is a promising approach for treating frontotemporal dementia and other neurodegenerative diseases. Here Nicholson et al.show that the prosaposin (PSAP) locus is associated with plasma PGRN levels and demonstrate that PSAP can alter PGRN levels and its oligomerization.
- Alexandra M. Nicholson
- , NiCole A. Finch
- & Rosa Rademakers
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Article
| Open AccessGenome-wide association study identifies 8p21.3 associated with persistent hepatitis B virus infection among Chinese
This genome-wide association study on persistent hepatitis B virus (HBV) infection among Chinese confirms previously associated genetic loci while discovering a novel protective locus at 8p21.3. The study also demonstrates the nearby gene INST10 suppresses HBV replication in vitro.
- Yuanfeng Li
- , Lanlan Si
- & Gangqiao Zhou
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Article
| Open AccessA genome-wide association scan implicates DCHS2, RUNX2, GLI3, PAX1 and EDAR in human facial variation
Humans show great diversity in facial appearance and this variation is highly heritable. Here, Andres Ruiz-Linares and colleagues examined facial features in admixed Latin Americans and identify genome-wide associations for 14 facial traits, including four gene loci (RUNX2, GLI3, DCHS2 and PAX1) influencing nose morphology.
- Kaustubh Adhikari
- , Macarena Fuentes-Guajardo
- & Andrés Ruiz-Linares
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Article
| Open AccessCommon genetic variation in ETV6 is associated with colorectal cancer susceptibility
Genome-wide association studies have been performed to identify genetic variants that are associated with susceptibility to colorectal cancer. Here, the authors expand on these studies and identify a variant that regulates the expression of ETV6 and find that over-expression of ETV6 blocks cell proliferation in vitro.
- Meilin Wang
- , Dongying Gu
- & Jinfei Chen
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Article
| Open AccessIdentification of four novel susceptibility loci for oestrogen receptor negative breast cancer
Oestrogen negative breast cancer is associated with a poor prognosis. In this study, the authors perform a meta-analysis of 11 breast cancer genome-wide association studies and identify four new loci associated with oestrogen negative breast cancer risk. These findings may aid in stratifying patients in the clinic.
- Fergus J. Couch
- , Karoline B. Kuchenbaecker
- & Antonis C. Antoniou
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Article
| Open AccessAtlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation
Over one hundred loci have been identified to be associated with the familial risk of prostate cancer but the functional effects are poorly understood. Here the authors use single-nucleotide variant and epigentic data to show an underlying genetic architecture marked by histone modification.
- Alexander Gusev
- , Huwenbo Shi
- & Bogdan Pasaniuc
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Article
| Open AccessMeta-analysis of gene–environment-wide association scans accounting for education level identifies additional loci for refractive error
This report by the Consortium for Refractive Error and Myopia uses gene-environment-wide interaction study (GEWIS) to identify genetic loci that affect environmental influence in myopia development, and identifies ethnic specific genetic loci that attribute to eye refractive errors.
- Qiao Fan
- , Virginie J. M. Verhoeven
- & Kari Matti Mäkelä
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Article
| Open AccessGenome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA
Circulating metabolites reflect human health and disease. Here, Kettunen et al. perform a genome-wide association study on 123 circulating metabolic traits and identify novel genetic loci influencing systemic metabolism. They also link new molecular pathways with a known cardiovascular risk factor Lp(a).
- Johannes Kettunen
- , Ayşe Demirkan
- & Mika Ala-Korpela
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Article
| Open AccessGenome-wide association analysis identifies novel loci for chronotype in 100,420 individuals from the UK Biobank
Here, Richa Saxena and colleagues perform a genome-wide association study (GWAS) of self-reported morningness/eveningness preference in the UKBiobank cohort, and identify new genetic loci that contribute to a person's chronotype.
- Jacqueline M. Lane
- , Irma Vlasac
- & Richa Saxena
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Article
| Open AccessMeta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia
Chronic lymphocytic leukemia is a highly inheritable cancer. Here the authors conduct a metaanalysis of four genome-wide association studies and identify three novel loci located near EOMES, SERPINB6 and LPPassociated with risk of this disease.
- Sonja I. Berndt
- , Nicola J. Camp
- & Susan L. Slager
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Article
| Open AccessA genome-wide association scan in admixed Latin Americans identifies loci influencing facial and scalp hair features
By examining Latin American individuals of mixed European, Native American and African ancestry, Adhikari et al. identify novel loci influencing various features of facial and scalp hair. The study also provides experimental evidence that one of the implicated genes (PRSS53) is expressed in the hair follicle and that the top associated variant alters processing of this enzyme.
- Kaustubh Adhikari
- , Tania Fontanil
- & Andrés Ruiz-Linares
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Article
| Open AccessGenome-wide association study identifies multiple susceptibility loci for craniofacial microsomia
Craniofacial microsomia is a congenital anomaly that affects the development of the skull. Here, the authors perform a genome-wide association study on patients in China and identify particular loci that provide insights into genetic mechanisms.
- Yong-Biao Zhang
- , Jintian Hu
- & Qingguo Zhang
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Article
| Open AccessGenome-wide association and high-resolution phenotyping link Oryza sativa panicle traits to numerous trait-specific QTL clusters
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
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Article
| Open AccessOpen access resources for genome-wide association mapping in rice
Understanding the link between genotype and phenotype can facilitate efforts by breeders to utilize natural variation and develop new crop varieties. Here the authors present a diverse germplasm collection, a high-density genotyping array and a set of bioinformatic tools to enable association mapping in rice.
- Susan R. McCouch
- , Mark H. Wright
- & Jason Mezey
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Article
| Open AccessGWAS of 89,283 individuals identifies genetic variants associated with self-reporting of being a morning person
Circadian rhythms and related behaviours vary across individuals. Here, a large genome-wide association study reveals common single nucleotide variants influencing whether an individual reports as being a ‘morning person’ by identifying 15 significant loci, including 7 near known circadian genes.
- Youna Hu
- , Alena Shmygelska
- & David A. Hinds
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Article
| Open AccessGenetic variants near MLST8 and DHX57 affect the epigenetic age of the cerebellum
This genome-wide association study identifies five significant SNPs in two loci which are associated with the epigenetic age of post-mortem cerebellar tissue according to a DNA methylation based biomarker of human aging.
- Ake T. Lu
- , Eilis Hannon
- & Steve Horvath
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Article
| Open AccessGenome-wide association study and targeted metabolomics identifies sex-specific association of CPS1 with coronary artery disease
Dietary choline metabolites, such as trimethylamine N-oxide and betaine, have been associated with coronary artery disease (CAD). Here, Hartiala et al. identify two genetic loci for betaine levels on chromosomes 2q34 and 5q14.1 and find that the 2q34 locus was also associated with other pathway intermediates, and decreased risk of CAD in women.
- Jaana A. Hartiala
- , W. H. Wilson Tang
- & Hooman Allayee
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Article
| Open AccessGenome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes
Here, Imamuraet al. conduct meta-analysis of genome-wide association studies to identify novel susceptibility loci for type 2 diabetes (T2D) in the Japanese population. By doing so, this study shows that both ethnicity-specific and ethnically-shared genetic loci can contribute to T2D risk.
- Minako Imamura
- , Atsushi Takahashi
- & Takashi Kadowaki
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Article
| Open AccessComplex disease and phenotype mapping in the domestic dog
The domestic dog is an important model organism for our understanding of cancer and other diseases. Here the authors conduct a genome-wide association study across multiple breeds and identify novel loci significantly associated with several complex diseases and morphological traits.
- Jessica J. Hayward
- , Marta G. Castelhano
- & Adam R. Boyko
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Article
| Open AccessGenetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
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.
- Cristian Pattaro
- , Alexander Teumer
- & Caroline S. Fox
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Article
| Open AccessGenome-wide association study identifies variation at 6q25.1 associated with survival in multiple myeloma
The prognosis of multiple myeloma patients varies widely. Here, to identify genetic factors associated with differing prognoses, the authors carried out a meta-analysis of four genome-wide association studies and identified a risk variant associated with survival interval.
- David C. Johnson
- , Niels Weinhold
- & Gareth J. Morgan
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Article
| Open AccessExome-wide association analysis reveals novel coding sequence variants associated with lipid traits in Chinese
An important risk factor for coronary artery disease is the level of blood lipids. Here the authors conduct an exome-wide association study in Chinese cohorts and identify three novel loci associated with lipid levels as well as three Asian-specific variants in known loci.
- Clara S. Tang
- , He Zhang
- & Wei Gao
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Article
| Open AccessA genome-wide association study identifies four novel susceptibility loci underlying inguinal hernia
Inguinal hernia has high lifetime prevalence, especially in men. This genome-wide association study identifies 4 loci to be associated with inguinal hernia, and shows expression of nearby genes in mouse connective tissues.
- Eric Jorgenson
- , Nadja Makki
- & Andrew Avins
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Article
| Open AccessThe genetic basis of natural variation in mushroom body size in Drosophila melanogaster
The mushroom bodies (MBs) in an insect brain integrate and process sensory information. Using fully sequenced/inbred lines of the Drosophila Genetic Reference Panel, this study performs genome wide association analyses and identifies candidate genes affecting MB size, and uses RNAi to functionally validate the identified loci.
- Liesbeth Zwarts
- , Lies Vanden Broeck
- & Patrick Callaerts