Genome-wide association analysis of 350 000 Caucasians from the UK Biobank identifies novel loci for asthma, hay fever and eczema.
Adult
Aged
Asthma
/ ethnology
Biological Specimen Banks
Eczema
/ ethnology
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
/ methods
Humans
Ki-1 Antigen
/ genetics
Linkage Disequilibrium
Male
Membrane Proteins
/ genetics
Middle Aged
Phenotype
Polymorphism, Single Nucleotide
Rhinitis, Allergic, Seasonal
/ ethnology
Tetraspanins
/ genetics
Transcription Factors
/ genetics
United Kingdom
/ ethnology
White People
/ genetics
Journal
Human molecular genetics
ISSN: 1460-2083
Titre abrégé: Hum Mol Genet
Pays: England
ID NLM: 9208958
Informations de publication
Date de publication:
01 12 2019
01 12 2019
Historique:
received:
07
03
2019
revised:
29
05
2019
accepted:
03
06
2019
pubmed:
31
7
2019
medline:
2
6
2020
entrez:
31
7
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31361310
pii: 5540983
doi: 10.1093/hmg/ddz175
pmc: PMC6969355
doi:
Substances chimiques
Ki-1 Antigen
0
Membrane Proteins
0
Myrf protein, human
0
TSPAN8 protein, human
0
Tetraspanins
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4022-4041Subventions
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press.
Références
Nat Genet. 2018 Jun;50(6):857-864
pubmed: 29785011
Nature. 2015 Oct 1;526(7571):82-90
pubmed: 26367797
J Allergy Clin Immunol. 2004 May;113(5):925-31
pubmed: 15131576
J Allergy Clin Immunol. 2014 Jun;133(6):1564-71
pubmed: 24388013
Proc Natl Acad Sci U S A. 2014 Dec 9;111(49):E5272-81
pubmed: 25422463
Cell Rep. 2016 Dec 13;17(11):2955-2965
pubmed: 27974209
Eur J Hum Genet. 2016 Aug;24(8):1202-5
pubmed: 26733288
Nat Genet. 2015 Dec;47(12):1449-1456
pubmed: 26482879
Allergy. 2016 Feb;71(2):230-8
pubmed: 26786172
Nat Genet. 2016 Oct;48(10):1279-83
pubmed: 27548312
Twin Res Hum Genet. 2008 Apr;11(2):121-31
pubmed: 18361712
Proc Natl Acad Sci U S A. 1998 Jan 20;95(2):588-93
pubmed: 9435236
Biopreserv Biobank. 2015 Oct;13(5):307-8
pubmed: 26484569
PLoS One. 2013 Jul 10;8(7):e67920
pubmed: 23874467
PLoS Med. 2005 Aug;2(8):e124
pubmed: 16060722
Curr Genomics. 2007 Nov;8(7):453-65
pubmed: 19412418
PLoS Genet. 2015 Mar 10;11(3):e1005076
pubmed: 25757221
Am J Respir Crit Care Med. 2015 Mar 1;191(5):530-7
pubmed: 25562107
Nat Genet. 2015 Mar;47(3):291-5
pubmed: 25642630
Nat Genet. 2012 Mar 18;44(4):369-75, S1-3
pubmed: 22426310
Nat Commun. 2018 Dec 3;9(1):5141
pubmed: 30510157
N Engl J Med. 2010 Sep 23;363(13):1211-1221
pubmed: 20860503
J Allergy Clin Immunol. 2016 Sep;138(3):676-699
pubmed: 27297995
Proc Natl Acad Sci U S A. 2012 Jan 24;109(4):1193-8
pubmed: 22223662
Nat Genet. 2012 Nov;44(11):1222-6
pubmed: 23042114
Allergy. 2012 Jan;67(1):83-90
pubmed: 21933193
Nat Genet. 2018 Jan;50(1):42-53
pubmed: 29273806
Nat Neurosci. 2005 Nov;8(11):1534-41
pubmed: 16234806
N Engl J Med. 2010 Jan 7;362(1):36-44
pubmed: 20032318
Am J Hum Genet. 2009 May;84(5):581-93
pubmed: 19426955
Ann Allergy Asthma Immunol. 2010 Aug;105(2):99-106; quiz 107-9, 117
pubmed: 20674819
Nature. 2011 Aug 10;476(7359):214-9
pubmed: 21833088
Hum Genomics. 2009 Oct;4(1):43-55
pubmed: 19951893
Cell. 2016 Nov 17;167(5):1415-1429.e19
pubmed: 27863252
Nat Commun. 2015 Nov 06;6:8804
pubmed: 26542096
Nat Genet. 2013 Aug;45(8):907-11
pubmed: 23817569
Am J Respir Crit Care Med. 2015 Sep 1;192(5):559-69
pubmed: 26030696
Immunol Rev. 2011 Jul;242(1):10-30
pubmed: 21682736
Allergy. 2009 Dec;64(12):1758-65
pubmed: 19839980
J Allergy Clin Immunol. 2006 Oct;118(4):942-8
pubmed: 17030250
Genome Res. 2001 May;11(5):863-74
pubmed: 11337480
Nat Genet. 2017 Dec;49(12):1752-1757
pubmed: 29083406
Eur J Hum Genet. 2012 Jul;20(7):801-5
pubmed: 22293688
Nat Genet. 2008 May;40(5):631-7
pubmed: 18372901
Nat Methods. 2010 Apr;7(4):248-9
pubmed: 20354512
Toxicol Sci. 2015 Jul;146(1):192-201
pubmed: 25918132
Am J Hum Genet. 2007 Sep;81(3):559-75
pubmed: 17701901
J Eur Acad Dermatol Venereol. 2012 Sep;26(9):1067-73
pubmed: 22243446
Am J Clin Nutr. 2008 Oct;88(4):941-9
pubmed: 18842780
Ann Rheum Dis. 2005 Nov;64 Suppl 4:iv70-6
pubmed: 16239393
Am J Hum Genet. 2012 May 4;90(5):809-20
pubmed: 22503634
Nat Genet. 2017 Feb;49(2):256-261
pubmed: 28067908
Nat Genet. 2018 Aug;50(8):1072-1080
pubmed: 30013184
J Allergy Clin Immunol. 2019 Feb;143(2):691-699
pubmed: 29679657
Bioinformatics. 2005 Aug 15;21(16):3439-40
pubmed: 16082012
Clin Exp Allergy. 2015 Jan;45(1):21-31
pubmed: 24766371
Asia Pac Allergy. 2011 Oct;1(3):157-67
pubmed: 22053313
Genet Res (Camb). 2010 Dec;92(5-6):371-9
pubmed: 21429269
Nat Genet. 2008 Apr;40(4):395-402
pubmed: 18311140