当前位置： SCI文献检索 > HUMAN MOLECULAR GENETICS期刊下所有文献 > Genome-wide association analysis of 350 000 Caucasians from the UK Biobank identifies novel loci for asthma, hay fever and eczema.

Genome-wide association analysis of 350 000 Caucasians from the UK Biobank identifies novel loci for asthma, hay fever and eczema.

Abstract：

:Even though heritability estimates suggest that the risk of asthma, hay fever and eczema is largely due to genetic factors, previous studies have not explained a large part of the genetics behind these diseases. In this genome-wide association study, we include 346 545 Caucasians from the UK Biobank to identify novel loci for asthma, hay fever and eczema and replicate novel loci in three independent cohorts. We further investigate if associated lead single nucleotide polymorphisms (SNPs) have a significantly larger effect for one disease compared to the other diseases, to highlight possible disease-specific effects. We identified 141 loci, of which 41 are novel, to be associated (P ≤ 3 × 10-8) with asthma, hay fever or eczema, analyzed separately or as disease phenotypes that includes the presence of different combinations of these diseases. The largest number of loci was associated with the combined phenotype (asthma/hay fever/eczema). However, as many as 20 loci had a significantly larger effect on hay fever/eczema only compared to their effects on asthma, while 26 loci exhibited larger effects on asthma compared with their effects on hay fever/eczema. At four of the novel loci, TNFRSF8, MYRF, TSPAN8, and BHMG1, the lead SNPs were in Linkage Disequilibrium (LD) (>0.8) with potentially casual missense variants. Our study shows that a large amount of the genetic contribution is shared between the diseases. Nonetheless, a number of SNPs have a significantly larger effect on one of the phenotypes, suggesting that part of the genetic contribution is more phenotype specific.

journal_name

Hum Mol Genet

journal_title

Human molecular genetics

authors

Johansson Å,Rask-Andersen M,Karlsson T,Ek WE

doi

10.1093/hmg/ddz175

subject

Has Abstract

pub_date

2019-12-01 00:00:00

pages

4022-4041

issue

23

eissn

0964-6906

issn

1460-2083

pii

5540983

journal_volume

28

pub_type

杂志文章

相关文献

HUMAN MOLECULAR GENETICS文献大全
  • Full-length dystrophin expression in half of the heart cells ameliorates beta-isoproterenol-induced cardiomyopathy in mdx mice.

    abstract：:Gene therapy holds great promise for curing Duchenne muscular dystrophy (DMD), the most common fatal inherited childhood muscle disease. Success of DMD gene therapy depends upon functional improvement in both skeletal and cardiac muscle. Numerous gene transfer studies have been performed to correct skeletal muscle pat...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddh174

    authors： Yue Y,Skimming JW,Liu M,Strawn T,Duan D

    更新日期：2004-08-01 00:00:00

  • Mitofusin 2 is necessary for striatal axonal projections of midbrain dopamine neurons.

    abstract：:Mitochondrial dysfunction is implicated in aging and degenerative disorders such as Parkinson's disease (PD). Continuous fission and fusion of mitochondria shapes their morphology and is essential to maintain oxidative phosphorylation. Loss-of-function mutations in PTEN-induced kinase1 (PINK1) or Parkin cause a recess...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/dds352

    authors： Lee S,Sterky FH,Mourier A,Terzioglu M,Cullheim S,Olson L,Larsson NG

    更新日期：2012-11-15 00:00:00

  • Evidence for inter-generational instability in the CAG repeat in the MJD1 gene and for conserved haplotypes at flanking markers amongst Japanese and Caucasian subjects with Machado-Joseph disease.

    abstract：:The size of the (CAG)n repeat array in the 3' end of the MJD1 gene and the haplotype at a series of microsatellite markers surrounding the MJD1 gene were examined in a large cohort of Japanese and Caucasian subjects affected with Machado-Joseph disease (MJD). Our data provide five novel observations. First, MJD is ass...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/4.7.1137

    authors： Takiyama Y,Igarashi S,Rogaeva EA,Endo K,Rogaev EI,Tanaka H,Sherrington R,Sanpei K,Liang Y,Saito M

    更新日期：1995-07-01 00:00:00

  • The Leri-Weill and Turner syndrome homeobox gene SHOX encodes a cell-type specific transcriptional activator.

    abstract：:Functional impairment of the human homeobox gene SHOX causes short stature and Madelung deformity in Leri-Weill syndrome (LWS) and has recently been implicated in additional skeletal malformations frequently observed in Turner syndrome. To enhance our understanding of the underlying mechanism of action, we have establ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/10.26.3083

    authors： Rao E,Blaschke RJ,Marchini A,Niesler B,Burnett M,Rappold GA

    更新日期：2001-12-15 00:00:00

  • Utrophin A is essential in mediating the functional adaptations of mdx mouse muscle following chronic AMPK activation.

    abstract：:Duchenne muscular dystrophy (DMD) is caused by the absence of dystrophin along muscle fibers. An attractive therapeutic avenue for DMD consists in the upregulation of utrophin A, a protein with high sequence identity and functional redundancy with dystrophin. Recent work has shown that pharmacological interventions th...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddu535

    authors： Al-Rewashdy H,Ljubicic V,Lin W,Renaud JM,Jasmin BJ

    更新日期：2015-03-01 00:00:00

  • Sub-physiological sarcoglycan expression contributes to compensatory muscle protection in mdx mice.

    abstract：:Sarcoglycans are a group of single-pass transmembrane glycoproteins. In striated muscle, sarcoglycans interact with dystrophin and other dystrophin-associated proteins (DAPs) to form the dystrophin-associated glycoprotein complex (DGC). The DGC protects the sarcolemma from contraction-induced injury. Duchenne muscular...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddp015

    authors： Li D,Long C,Yue Y,Duan D

    更新日期：2009-04-01 00:00:00

  • Mutant SPTLC1 dominantly inhibits serine palmitoyltransferase activity in vivo and confers an age-dependent neuropathy.

    abstract：:Mutations in enzymes involved in sphingolipid metabolism and trafficking cause a variety of neurological disorders, but details of the molecular pathophysiology remain obscure. SPTLC1 encodes one subunit of serine palmitoyltransferase (SPT), the rate-limiting enzyme in sphingolipid synthesis. Mutations in SPTLC1 cause...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddi380

    authors： McCampbell A,Truong D,Broom DC,Allchorne A,Gable K,Cutler RG,Mattson MP,Woolf CJ,Frosch MP,Harmon JM,Dunn TM,Brown RH Jr

    更新日期：2005-11-15 00:00:00

  • Hypermorphic and hypomorphic AARS alleles in patients with CMT2N expand clinical and molecular heterogeneities.

    abstract：:Aminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed enzymes implicated in several dominant and recessive disease phenotypes. The canonical function of ARSs is to couple an amino acid to a cognate transfer RNA (tRNA). We identified three novel disease-associated missense mutations in the alanyl-tRNA synthetase...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddy290

    authors： Weterman MAJ,Kuo M,Kenter SB,Gordillo S,Karjosukarso DW,Takase R,Bronk M,Oprescu S,van Ruissen F,Witteveen RJW,Bienfait HME,Breuning M,Verhamme C,Hou YM,de Visser M,Antonellis A,Baas F

    更新日期：2018-12-01 00:00:00

  • Urogenital development in Pallister-Hall syndrome is disrupted in a cell-lineage-specific manner by constitutive expression of GLI3 repressor.

    abstract：:Pallister-Hall syndrome (PHS) is a rare disorder caused by mutations in GLI3 that produce a transcriptional repressor (GLI3R). Individuals with PHS present with a variably penetrant variety of urogenital system malformations, including renal aplasia or hypoplasia, hydroureter, hydronephrosis or a common urogenital sin...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddv483

    authors： Blake J,Hu D,Cain JE,Rosenblum ND

    更新日期：2016-02-01 00:00:00

  • Uromodulin is expressed in renal primary cilia and UMOD mutations result in decreased ciliary uromodulin expression.

    abstract：:Uromodulin (UMOD) mutations are responsible for three autosomal dominant tubulo-interstitial nephropathies including medullary cystic kidney disease type 2 (MCKD2), familial juvenile hyperuricemic nephropathy and glomerulocystic kidney disease. Symptoms include renal salt wasting, hyperuricemia, gout, hypertension and...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddq077

    authors： Zaucke F,Boehnlein JM,Steffens S,Polishchuk RS,Rampoldi L,Fischer A,Pasch A,Boehm CW,Baasner A,Attanasio M,Hoppe B,Hopfer H,Beck BB,Sayer JA,Hildebrandt F,Wolf MT

    更新日期：2010-05-15 00:00:00

  • PAX4 gene variations predispose to ketosis-prone diabetes.

    abstract：:Ketosis-prone diabetes (KPD) is a rare form of type 2 diabetes, mostly observed in subjects of west African origin (west Africans and African-Americans), characterized by fulminant and phasic insulin dependence, but lacking markers of autoimmunity observed in type 1 diabetes. PAX4 is a transcription factor essential f...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddh341

    authors： Mauvais-Jarvis F,Smith SB,Le May C,Leal SM,Gautier JF,Molokhia M,Riveline JP,Rajan AS,Kevorkian JP,Zhang S,Vexiau P,German MS,Vaisse C

    更新日期：2004-12-15 00:00:00

  • The origin and loss of the ubiquitin activating enzyme gene on the mammalian Y chromosome.

    abstract：:Mammalian sex chromosomes are thought to be descended from a homologous pair of autosomes: a testis-determining allele which defined the Y chromosome arose, recombination between the nascent X and Y chromosomes became restricted and the Y chromosome gradually lost its non-essential genetic functions. This model was or...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/7.3.429

    authors： Mitchell MJ,Wilcox SA,Watson JM,Lerner JL,Woods DR,Scheffler J,Hearn JP,Bishop CE,Graves JA

    更新日期：1998-03-01 00:00:00

  • Primary angle closure glaucoma (PACG) susceptibility gene PLEKHA7 encodes a novel Rac1/Cdc42 GAP that modulates cell migration and blood-aqueous barrier function.

    abstract：:PLEKHA7, a gene recently associated with primary angle closure glaucoma (PACG), encodes an apical junctional protein expressed in components of the blood aqueous barrier (BAB). We found that PLEKHA7 is down-regulated in lens epithelial cells and in iris tissue of PACG patients. PLEKHA7 expression also correlated with ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddx292

    authors： Lee MC,Shei W,Chan AS,Chua BT,Goh SR,Chong YF,Hilmy MH,Nongpiur ME,Baskaran M,Khor CC,Aung T,Hunziker W,Vithana EN

    更新日期：2017-10-15 00:00:00

  • Evolution of the sperm methylome of primates is associated with retrotransposon insertions and genome instability.

    abstract：:Changes in gene expression resulting from epigenetic and/or genetic changes play an important role in the evolutionary divergence of phenotypes. To explore how epigenetic and genetic changes are linked during primate evolution, we have compared the genome-wide DNA methylation profiles (methylomes) of humans and chimpa...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddx236

    authors： Fukuda K,Inoguchi Y,Ichiyanagi K,Ichiyanagi T,Go Y,Nagano M,Yanagawa Y,Takaesu N,Ohkawa Y,Imai H,Sasaki H

    更新日期：2017-09-15 00:00:00

  • Genome-wide scan identifies CDH13 as a novel susceptibility locus contributing to blood pressure determination in two European populations.

    abstract：:Hypertension is a complex disease that affects a large proportion of adult population. Although approximately half of the inter-individual variance in blood pressure (BP) level is heritable, identification of genes responsible for its regulation has remained challenging. Genome-wide association study (GWAS) is a novel...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddp135

    authors： Org E,Eyheramendy S,Juhanson P,Gieger C,Lichtner P,Klopp N,Veldre G,Döring A,Viigimaa M,Sõber S,Tomberg K,Eckstein G,KORA.,Kelgo P,Rebane T,Shaw-Hawkins S,Howard P,Onipinla A,Dobson RJ,Newhouse SJ,Brown M,Domini

    更新日期：2009-06-15 00:00:00

  • Gene therapy of muscular dystrophy.

    abstract：:Development of gene therapy for the muscular dystrophies represents a daunting challenge requiring significant advances in our knowledge of the defective genes, muscle promoters, viral vectors, immune system surveillance and methods for systemic delivery of vectors. However, tremendous progress has been made in develo...

    journal_title：Human molecular genetics

    pub_type： 杂志文章,评审

    doi：10.1093/hmg/11.20.2355

    authors： Chamberlain JS

    更新日期：2002-10-01 00:00:00

  • Functional role for senataxin, defective in ataxia oculomotor apraxia type 2, in transcriptional regulation.

    abstract：:Ataxia oculomotor apraxia type 2 (AOA2) is an autosomal recessive neurodegenerative disorder characterized by cerebellar ataxia and oculomotor apraxia. The gene mutated in AOA2, SETX, encodes senataxin, a putative DNA/RNA helicase which shares high homology to the yeast Sen1p protein and has been shown to play a role ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddp278

    authors： Suraweera A,Lim Y,Woods R,Birrell GW,Nasim T,Becherel OJ,Lavin MF

    更新日期：2009-09-15 00:00:00

  • The combination of a genome-wide association study of lymphocyte count and analysis of gene expression data reveals novel asthma candidate genes.

    abstract：:Recent genome-wide association studies (GWAS) have identified a number of novel genetic associations with complex human diseases. In spite of these successes, results from GWAS generally explain only a small proportion of disease heritability, an observation termed the 'missing heritability problem'. Several sources f...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/dds021

    authors： Cusanovich DA,Billstrand C,Zhou X,Chavarria C,De Leon S,Michelini K,Pai AA,Ober C,Gilad Y

    更新日期：2012-05-01 00:00:00

  • Identification and characterization of a novel gene Saf transcribed from the opposite strand of Fas.

    abstract：:Apoptosis is a morphologically distinct form of cell death involved in many physiological and pathological processes. The regulation of Fas/Apo-1 involved in membrane-mediated apoptosis has also been known to play crucial roles in many systems. More and more naturally occurring antisense RNAs are now known to regulate...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddi156

    authors： Yan MD,Hong CC,Lai GM,Cheng AL,Lin YW,Chuang SE

    更新日期：2005-06-01 00:00:00

  • Enzyme replacement therapy in mice lacking arylsulfatase B targets bone-remodeling cells, but not chondrocytes.

    abstract：:Mucopolysaccharidosis type VI (MPS-VI), caused by mutational inactivation of the glycosaminoglycan-degrading enzyme arylsulfatase B (Arsb), is a lysosomal storage disorder primarily affecting the skeleton. We have previously reported that Arsb-deficient mice display high trabecular bone mass and impaired skeletal grow...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddaa006

    authors： Hendrickx G,Danyukova T,Baranowsky A,Rolvien T,Angermann A,Schweizer M,Keller J,Schröder J,Meyer-Schwesinger C,Muschol N,Paganini C,Rossi A,Amling M,Pohl S,Schinke T

    更新日期：2020-03-27 00:00:00

  • Inactivation of both APC alleles in an early stage of colon adenomas in a patient with familial adenomatous polyposis (FAP).

    abstract：:To examine whether the dosage effect of germ-line mutations in patients with familial adenomatous polyposis (FAP) is sufficient to cause colorectal adenomas, or an additional somatic mutation of the normal allele is required as well, we have investigated somatic mutations of the APC gene in multiple adenomas developed...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/1.6.387

    authors： Ichii S,Horii A,Nakatsuru S,Furuyama J,Utsunomiya J,Nakamura Y

    更新日期：1992-09-01 00:00:00

  • Insertional mutation by transposable element, L1, in the DMD gene results in X-linked dilated cardiomyopathy.

    abstract：:X-linked dilated cardiomyopathy (XLDCM) is a clinical phenotype of dystrophinopathy which is characterized by preferential myocardial involvement without any overt clinical signs of skeletal myopathy. To date, several mutations in the Duchenne muscular dystrophy gene, DMD , have been identified in patients with XLDCM,...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/7.7.1129

    authors： Yoshida K,Nakamura A,Yazaki M,Ikeda S,Takeda S

    更新日期：1998-07-01 00:00:00

  • Polar substitutions in helix 3 of the prion protein produce transmembrane isoforms that disturb vesicle trafficking.

    abstract：:Prion diseases encompass a diverse group of neurodegenerative conditions characterized by the accumulation of misfolded prion protein (PrP) isoforms. Other conformational variants of PrP have also been proposed to contribute to neurotoxicity in prion diseases, including misfolded intermediates as well as cytosolic and...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddt276

    authors： Sanchez-Garcia J,Arbelaez D,Jensen K,Rincon-Limas DE,Fernandez-Funez P

    更新日期：2013-11-01 00:00:00

  • Hypoxic drive caused type 3 neovascularization in a preclinical model of exudative age-related macular degeneration.

    abstract：:Hypoxia associated with the high metabolic demand of rods has been implicated in the pathology of age-related macular degeneration (AMD), the most common cause of adult blindness in the developed world. The majority of AMD-associated severe vision loss cases are due to exudative AMD, characterized by neovascularizatio...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddz159

    authors： Zhang L,Cui X,Han Y,Park KS,Gao X,Zhang X,Yuan Z,Hu Y,Hsu CW,Li X,Bassuk AG,Mahajan VB,Wang NK,Tsang SH

    更新日期：2019-10-15 00:00:00

  • Multiple deletions of mtDNA in two brothers with sideroblastic anemia and mitochondrial myopathy and in their asymptomatic mother.

    abstract：:Two brothers presented with a clinical picture characterized by sideroblastic anemia, mild pancreatic insufficiency and progressive muscle weakness. The presence of an associated permanent basal lactic acidemia raised the suspicion of a mitochondrial disease. A muscle biopsy performed in both siblings proved the prese...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/3.11.1945

    authors： Casademont J,Barrientos A,Cardellach F,Rötig A,Grau JM,Montoya J,Beltrán B,Cervantes F,Rozman C,Estivill X

    更新日期：1994-11-01 00:00:00

  • The adipocyte differentiation protein APMAP is an endogenous suppressor of Aβ production in the brain.

    abstract：:The deposition of amyloid-beta (Aβ) aggregates in the brain is a major pathological hallmark of Alzheimer's disease (AD). Aβ is generated from the cleavage of C-terminal fragments of the amyloid precursor protein (APP-CTFs) by γ-secretase, an intramembrane-cleaving protease with multiple substrates, including the Notc...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddu449

    authors： Mosser S,Alattia JR,Dimitrov M,Matz A,Pascual J,Schneider BL,Fraering PC

    更新日期：2015-01-15 00:00:00

  • Thermosensory and mechanosensory perception in human genetic disease.

    abstract：:Peripheral sensory perception is established through an elaborate network of specialized neurons that mediate the translation of extraorganismal stimuli through the use of a broad array of receptors and downstream effector molecules. Studies of human genetic disorders, as well as mouse and other animal models, have id...

    journal_title：Human molecular genetics

    pub_type： 杂志文章,评审

    doi：10.1093/hmg/ddp412

    authors： Tan PL,Katsanis N

    更新日期：2009-10-15 00:00:00

  • The HLA class III subregion is responsible for an increased breast cancer risk.

    abstract：:BRCA1 and BRCA2 germline mutations account for <5% of breast cancer cases. Less penetrant breast cancer susceptibility genes are likely to exist. Earlier studies have suggested involvement of the HLA region. The HLA region was genotyped with 24 microsatellite markers and markers for two single nucleotide polymorphisms...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddg245

    authors： de Jong MM,Nolte IM,de Vries EG,Schaapveld M,Kleibeuker JH,Oosterom E,Oosterwijk JC,van der Hout AH,van der Steege G,Bruinenberg M,Boezen HM,Te Meerman GJ,van der Graaf WT

    更新日期：2003-09-15 00:00:00

  • DNA methylation profiling in human Huntington's disease brain.

    abstract：:Despite extensive progress in Huntington's disease (HD) research, very little is known about the association of epigenetic variation and HD pathogenesis in human brain tissues. Moreover, its contribution to the tissue-specific transcriptional regulation of the huntingtin gene (HTT), in which HTT expression levels are ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddw076

    authors： De Souza RA,Islam SA,McEwen LM,Mathelier A,Hill A,Mah SM,Wasserman WW,Kobor MS,Leavitt BR

    更新日期：2016-05-15 00:00:00

  • Gclc deficiency in mouse CNS causes mitochondrial damage and neurodegeneration.

    abstract：:Gamma glutamyl cysteine ligase (GCL) is the rate-limiting enzyme for intracellular glutathione (GSH) synthesis. The GSH concentration and GCL activity are declining with age in the central nervous system (CNS), and is accompanied by elevated reactive oxygen species (ROS). To study the biological effects of low GSH lev...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddx040

    authors： Feng W,Rosca M,Fan Y,Hu Y,Feng P,Lee HG,Monnier VM,Fan X

    更新日期：2017-04-01 00:00:00