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dc.contributor.authorFawcett, Katherine A
dc.contributor.authorObeidat, Ma'en
dc.contributor.authorMelbourne, Carl
dc.contributor.authorShrine, Nick
dc.contributor.authorGuyatt, Anna L
dc.contributor.authorJohn, Catherine
dc.contributor.authorLuan, Jian'an
dc.contributor.authorRichmond, Anne
dc.contributor.authorMoksnes, Marta R
dc.contributor.authorGranell, Raquel
dc.contributor.authorWeiss, Stefan
dc.contributor.authorImboden, Medea
dc.contributor.authorMay-Wilson, Sebastian
dc.contributor.authorHysi, Pirro
dc.contributor.authorBoutin, Thibaud S
dc.contributor.authorPortas, Laura
dc.contributor.authorFlexeder, Claudia
dc.contributor.authorHarris, Sarah E
dc.contributor.authorWang, Carol A
dc.contributor.authorLyytikäinen, Leo-Pekka
dc.contributor.authorPalviainen, Teemu
dc.contributor.authorFoong, Rachel E
dc.contributor.authorKeidel, Dirk
dc.contributor.authorMinelli, Cosetta
dc.contributor.authorLangenberg, Claudia
dc.contributor.authorBossé, Yohan
dc.contributor.authorVan den Berge, Maarten
dc.contributor.authorSin, Don D
dc.contributor.authorHao, Ke
dc.contributor.authorCampbell, Archie
dc.contributor.authorPorteous, David
dc.contributor.authorPadmanabhan, Sandosh
dc.contributor.authorSmith, Blair H
dc.contributor.authorEvans, David M
dc.contributor.authorRing, Sue
dc.contributor.authorLanghammer, Arnulf
dc.contributor.authorHveem, Kristian
dc.contributor.authorWiller, Cristen
dc.contributor.authorEwert, Ralf
dc.contributor.authorStubbe, Beate
dc.contributor.authorPirastu, Nicola
dc.contributor.authorKlaric, Lucija
dc.contributor.authorJoshi, Peter K
dc.contributor.authorPatasova, Karina
dc.contributor.authorMassimo, Mangino
dc.contributor.authorPolasek, Ozren
dc.contributor.authorStarr, John M
dc.contributor.authorKarrasch, Stefan
dc.contributor.authorStrauch, Konstantin
dc.contributor.authorMeitinger, Thomas
dc.contributor.authorRudan, Igor
dc.contributor.authorRantanen, Taina
dc.contributor.authorPietiläinen, Kirsi
dc.contributor.authorKähönen, Mika
dc.contributor.authorRaitakari, Olli T
dc.contributor.authorHall, Graham L
dc.contributor.authorSly, Peter D
dc.contributor.authorPennell, Craig E
dc.contributor.authorKaprio, Jaakko
dc.contributor.authorLehtimäki, Terho
dc.contributor.authorVitart, Veronique
dc.contributor.authorDeary, Ian J
dc.contributor.authorJarvis, Debbie
dc.contributor.authorWilson, James F
dc.contributor.authorSpector, Tim
dc.contributor.authorProbst-Hensch, Nicole
dc.contributor.authorWareham, Nicholas J
dc.contributor.authorVölzke, Henry
dc.contributor.authorHenderson, John
dc.contributor.authorStrachan, David P
dc.contributor.authorBrumpton, Ben M
dc.contributor.authorHayward, Caroline
dc.contributor.authorHall, Ian P
dc.contributor.authorTobin, Martin D
dc.contributor.authorWain, Louise V
dc.date.accessioned2022-01-08T00:31:01Z
dc.date.available2022-01-08T00:31:01Z
dc.date.issued2020
dc.identifier.issn2398-502X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332463
dc.description.abstractBackground: Lung function is highly heritable and differs between the sexes throughout life. However, little is known about sex-differential genetic effects on lung function. We aimed to conduct the first genome-wide genotype-by-sex interaction study on lung function to identify genetic effects that differ between males and females. Methods: We tested for interactions between 7,745,864 variants and sex on spirometry-based measures of lung function in UK Biobank (N=303,612), and sought replication in 75,696 independent individuals from the SpiroMeta consortium. Results: Five independent single-nucleotide polymorphisms (SNPs) showed genome-wide significant (P<5x10 -8) interactions with sex on lung function, and 21 showed suggestive interactions (P<1x10 -6). The strongest signal, from rs7697189 (chr4:145436894) on forced expiratory volume in 1 second (FEV 1) (P=3.15x10 -15), was replicated (P=0.016) in SpiroMeta. The C allele increased FEV 1 more in males (untransformed FEV 1 β=0.028 [SE 0.0022] litres) than females (β=0.009 [SE 0.0014] litres), and this effect was not accounted for by differential effects on height, smoking or pubertal age. rs7697189 resides upstream of the hedgehog-interacting protein ( HHIP) gene and was previously associated with lung function and HHIP lung expression. We found HHIP expression was significantly different between the sexes (P=6.90x10 -6), but we could not detect sex differential effects of rs7697189 on expression. Conclusions: We identified a novel genotype-by-sex interaction at a putative enhancer region upstream of the HHIP gene. Establishing the mechanism by which HHIP SNPs have different effects on lung function in males and females will be important for our understanding of lung health and diseases in both sexes.
dc.publisherF1000 Research Ltd
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectHHIP
dc.subjectexpression
dc.subjectgenome-wide interaction study
dc.subjectlung function
dc.subjectsex
dc.titleVariants associated with HHIP expression have sex-differential effects on lung function.
dc.typeArticle
dc.publisher.departmentMrc Epidemiology Unit
dc.publisher.departmentoffice of The School of Clinical Medicine
dc.date.updated2022-01-07T12:42:21Z
prism.publicationDate2020
prism.publicationNameWellcome Open Res
prism.startingPage111
prism.volume5
dc.identifier.doi10.17863/CAM.79909
dcterms.dateAccepted2021-05-19
rioxxterms.versionofrecord10.12688/wellcomeopenres.15846.2
rioxxterms.versionVoR
dc.contributor.orcidFawcett, Katherine A [0000-0002-6675-2112]
dc.contributor.orcidObeidat, Ma'en [0000-0002-5443-2752]
dc.contributor.orcidShrine, Nick [0000-0003-3641-4371]
dc.contributor.orcidWeiss, Stefan [0000-0002-3553-4315]
dc.contributor.orcidMay-Wilson, Sebastian [0000-0003-2668-5717]
dc.contributor.orcidBoutin, Thibaud S [0000-0003-4754-1675]
dc.contributor.orcidPortas, Laura [0000-0003-1789-1893]
dc.contributor.orcidHarris, Sarah E [0000-0002-4941-5106]
dc.contributor.orcidLyytikäinen, Leo-Pekka [0000-0002-7200-5455]
dc.contributor.orcidPalviainen, Teemu [0000-0002-7847-8384]
dc.contributor.orcidKeidel, Dirk [0000-0003-4706-5728]
dc.contributor.orcidMinelli, Cosetta [0000-0001-9166-3958]
dc.contributor.orcidLangenberg, Claudia [0000-0002-5017-7344]
dc.contributor.orcidBossé, Yohan [0000-0002-3067-3711]
dc.contributor.orcidVan den Berge, Maarten [0000-0002-9336-7340]
dc.contributor.orcidSin, Don D [0000-0002-0756-6643]
dc.contributor.orcidCampbell, Archie [0000-0003-0198-5078]
dc.contributor.orcidPorteous, David [0000-0003-1249-6106]
dc.contributor.orcidPadmanabhan, Sandosh [0000-0003-3869-5808]
dc.contributor.orcidSmith, Blair H [0000-0002-5362-9430]
dc.contributor.orcidRing, Sue [0000-0003-3103-9330]
dc.contributor.orcidRantanen, Taina [0000-0002-1604-1945]
dc.contributor.orcidPennell, Craig E [0000-0002-0937-6165]
dc.contributor.orcidKaprio, Jaakko [0000-0002-3716-2455]
dc.contributor.orcidVitart, Veronique [0000-0002-4991-3797]
dc.contributor.orcidHayward, Caroline [0000-0002-9405-9550]
dc.contributor.orcidHall, Ian P [0000-0001-9933-3216]
dc.contributor.orcidWain, Louise V [0000-0003-4951-1867]
dc.identifier.eissn2398-502X
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (MC_UU_12015/1)
pubs.funder-project-idMedical Research Council (MR/N003284/1)
pubs.funder-project-idMedical Research Council (G1000143)
pubs.funder-project-idMedical Research Council (G0500300)
pubs.funder-project-idMedical Research Council (G0401527)
pubs.funder-project-idMRC (MC_UU_00006/1)
pubs.funder-project-idWellcome Trust (082893/Z/07/Z)
pubs.funder-project-idTCC (None)
cam.issuedOnline2020-06-01
cam.depositDate2022-01-07
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International