A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
Variants associated with HHIP expression have sex-differential effects on lung function [version 1; peer review: 2 approved] (2020)
Fawcett, 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]. Wellcome Open Research, 5, Article 111. https://doi.org/10.12688/wellcomeopenres.15846.1
JYU-tekijät tai -toimittajat
Julkaisun tiedot
Julkaisun kaikki tekijät tai toimittajat: Fawcett, KA; Obeidat, M; Melbourne, C; Shrine, N; Guyatt, AL; John, C; Luan, J; Richmond, A; Moksnes, MR; Granell, R; et al.
Lehti tai sarja: Wellcome Open Research
eISSN: 2398-502X
Julkaisuvuosi: 2020
Volyymi: 5
Artikkelinumero: 111
Kustantaja: Wellcome Trust
Julkaisumaa: Britannia
Julkaisun kieli: englanti
DOI: https://doi.org/10.12688/wellcomeopenres.15846.1
Julkaisun avoin saatavuus: Avoimesti saatavilla
Julkaisukanavan avoin saatavuus: Kokonaan avoin julkaisukanava
Julkaisu on rinnakkaistallennettu (JYX): https://jyx.jyu.fi/handle/123456789/71082
Tiivistelmä
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.
YSO-asiasanat: hengityselimet; keuhkot; toimintakyky; geneettiset tekijät; geeniekspressio; genotyyppi; sukupuoli
Vapaat asiasanat: genome-wide interaction study; lung function; sex; HHIP; expression
Liittyvät organisaatiot
OKM-raportointi: Kyllä
Raportointivuosi: 2020
JUFO-taso: 0
