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dc.contributor.authorFawcett, KA
dc.contributor.authorObeidat, M
dc.contributor.authorMelbourne, C
dc.contributor.authorShrine, N
dc.contributor.authorGuyatt, AL
dc.contributor.authorJohn, C
dc.contributor.authorLuan, J
dc.contributor.authorRichmond, A
dc.contributor.authorMoksnes, MR
dc.contributor.authorGranell, R
dc.contributor.authorWeiss, S
dc.contributor.authorImboden, M
dc.contributor.authorMay-Wilson, S
dc.contributor.authorHysi, P
dc.contributor.authorBoutin, TS
dc.contributor.authorPortas, L
dc.contributor.authorFlexeder, C
dc.contributor.authorHarris, SE
dc.contributor.authorWang, CA
dc.contributor.authorLyytikäinen, LP
dc.contributor.authorPalviainen, T
dc.contributor.authorFoong, RE
dc.contributor.authorKeidel, D
dc.contributor.authorMinelli, C
dc.contributor.authorLangenberg, C
dc.contributor.authorBossé, Y
dc.contributor.authorVan den Berge, M
dc.contributor.authorSin, DD
dc.contributor.authorHao, K
dc.contributor.authorCampbell, A
dc.contributor.authorPorteous, D
dc.contributor.authorPadmanabhan, S
dc.contributor.authorSmith, BH
dc.contributor.authorEvans, DM
dc.contributor.authorRing, S
dc.contributor.authorLanghammer, A
dc.contributor.authorHveem, K
dc.contributor.authorWiller, C
dc.contributor.authorEwert, R
dc.contributor.authorStubbe, B
dc.contributor.authorPirastu, N
dc.contributor.authorKlaric, L
dc.contributor.authorJoshi, PK
dc.contributor.authorPatasova, K
dc.contributor.authorMassimo, M
dc.contributor.authorPolasek, O
dc.contributor.authorStarr, JM
dc.contributor.authorKarrasch, S
dc.contributor.authorStrauch, K
dc.contributor.authorMeitinger, T
dc.contributor.authorRudan, I
dc.contributor.authorRantanen, T.
dc.contributor.authorPietiläinen, K
dc.contributor.authorKähönen, M
dc.contributor.authorRaitakari, OT
dc.contributor.authorHall, GL
dc.contributor.authorSly, PD
dc.contributor.authorPennell, CE
dc.contributor.authorKaprio, J
dc.contributor.authorLehtimäki, T
dc.contributor.authorVitart, V
dc.contributor.authorDeary, IJ
dc.contributor.authorJarvis, D
dc.contributor.authorWilson, JF
dc.contributor.authorSpector, T
dc.contributor.authorProbst-Hensch, N
dc.contributor.authorWareham, NJ
dc.contributor.authorVölzke, H
dc.contributor.authorHenderson, J
dc.contributor.authorStrachan, DP
dc.contributor.authorBrumpton, BM
dc.contributor.authorHayward, C
dc.contributor.authorHall, IP
dc.contributor.authorTobin, MD
dc.contributor.authorWain, LV
dc.date.accessioned2020-07-06T09:33:19Z
dc.date.available2020-07-06T09:33:19Z
dc.date.issued2020
dc.identifier.citationFawcett, K., Obeidat, M., Melbourne, C., Shrine, N., Guyatt, A., John, C., Luan, J., Richmond, A., Moksnes, M., Granell, R., Weiss, S., Imboden, M., May-Wilson, S., Hysi, P., Boutin, T., Portas, L., Flexeder, C., Harris, S., Wang, C., . . . Wain, L. (2020). Variants associated with HHIP expression have sex-differential effects on lung function [version 1; peer review: 2 approved]. <i>Wellcome Open Research</i>, <i>5</i>, Article 111. <a href="https://doi.org/10.12688/wellcomeopenres.15846.1" target="_blank">https://doi.org/10.12688/wellcomeopenres.15846.1</a>
dc.identifier.otherCONVID_35892372
dc.identifier.urihttps://jyx.jyu.fi/handle/123456789/71082
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 (FEV1) (P=3.15x10-15), was replicated (P=0.016) in SpiroMeta. The C allele increased FEV1 more in males (untransformed FEV1 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.en
dc.format.mimetypeapplication/pdf
dc.languageeng
dc.language.isoeng
dc.publisherWellcome Trust
dc.relation.ispartofseriesWellcome Open Research
dc.rightsCC BY 4.0
dc.subject.othergenome-wide interaction study
dc.subject.otherlung function
dc.subject.othersex
dc.subject.otherHHIP
dc.subject.otherexpression
dc.titleVariants associated with HHIP expression have sex-differential effects on lung function [version 1; peer review: 2 approved]
dc.typearticle
dc.identifier.urnURN:NBN:fi:jyu-202007065255
dc.contributor.laitosLiikuntatieteellinen tiedekuntafi
dc.contributor.laitosFaculty of Sport and Health Sciencesen
dc.contributor.oppiaineGerontologia ja kansanterveysfi
dc.contributor.oppiaineGerontology and Public Healthen
dc.type.urihttp://purl.org/eprint/type/JournalArticle
dc.description.reviewstatuspeerReviewed
dc.relation.issn2398-502X
dc.relation.volume5
dc.type.versionacceptedVersion
dc.rights.copyright© Authors, 2020
dc.rights.accesslevelopenAccessfi
dc.subject.ysogenotyyppi
dc.subject.ysotoimintakyky
dc.subject.ysokeuhkot
dc.subject.ysogeneettiset tekijät
dc.subject.ysosukupuoli
dc.subject.ysogeeniekspressio
dc.subject.ysohengityselimet
dc.format.contentfulltext
jyx.subject.urihttp://www.yso.fi/onto/yso/p8863
jyx.subject.urihttp://www.yso.fi/onto/yso/p10213
jyx.subject.urihttp://www.yso.fi/onto/yso/p3185
jyx.subject.urihttp://www.yso.fi/onto/yso/p21661
jyx.subject.urihttp://www.yso.fi/onto/yso/p5291
jyx.subject.urihttp://www.yso.fi/onto/yso/p25831
jyx.subject.urihttp://www.yso.fi/onto/yso/p3186
dc.rights.urlhttps://creativecommons.org/licenses/by/4.0/
dc.relation.doi10.12688/wellcomeopenres.15846.1
jyx.fundinginformationAcademy of Finland (213506) (T.R.)


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