6533b820fe1ef96bd1279109
RESEARCH PRODUCT
SNPs associated withHHIPexpression have differential effects on lung function in males and females
Peter D. SlyRe FoongRe FoongOzren PolasekNicole Probst-henschNicole Probst-henschIan P. HallGraham L. HallGraham L. HallTobinTobinPirro G. HysiTeemu PalviainenMika KähönenVeronique VitartLouise V. WainLouise V. WainCarl A. MelbourneDon D. SinAnna L. GuyattHenry VölzkeCa WangKatherine A. FawcettDavid J. PorteousJohn M. StarrClaudia LangenbergIgor RudanKe HaoStefan WeissTerho LehtimäkiKirsi H. PietiläinenDavid M. EvansIan J. DearyJian'an LuanJames F. WilsonJames F. WilsonDavid P. StrachanTaina RantanenCatherine JohnNicola PirastuO T RaitakariO T RaitakariBerge M Van DenKarina PatasovaClaudia FlexederMedea ImbodenMedea ImbodenThibaud BoutinMangino MassimoArchie CampbellLucija KlaricLeo-pekka LyytikäinenNick ShrineSebastian May-wilsonBeate StubbeRalf EwertDirk KeidelDirk KeidelSarah E. HarrisTim D. SpectorMa'en ObeidatJohn HendersonCosetta MinelliMoksnesRaquel GranellBlair H. SmithArnulf LanghammerCraig E. PennellNicholas J. WarehamCaroline HaywardBen Michael BrumptonBen Michael BrumptonYohan BosséPeter K. JoshiSusan M. RingSandosh PadmanabhanCristen J. WillerKristian HveemDeborah JarvisJ KaprioLaura PortasAnne Richmondsubject
Spirometry0303 health sciencesCOPDmedicine.medical_specialtyLungmedicine.diagnostic_testSingle-nucleotide polymorphismBiologymedicine.disease03 medical and health sciences0302 clinical medicinemedicine.anatomical_structureEndocrinology030228 respiratory systemInternal medicinemedicineSNPAlleleBeta (finance)Lung function030304 developmental biologydescription
AbstractAdult lung function is highly heritable and 279 genetic loci were recently reported as associated with spirometry-based measures of lung function. Though lung development and function differ between males and females throughout life, there has been no genome-wide study to identify genetic variants with differential effects on lung function in males and females. Here, we present the first genome-wide genotype-by-sex interaction study on four lung function traits in 303,612 participants from the UK Biobank. We detected five SNPs showing genome-wide significant (P<5 × 10−8) interactions with sex on lung function, as well as 21 suggestively significant interactions (P<1 × 10−6). The strongest sex interaction signal came from rs7697189 at 4:145436894 on forced expiratory volume in 1 second (FEV1) (P = 3.15 × 10−15), and was replicated (P = 0.016) in 75,696 individuals in the SpiroMeta consortium. Sex-stratified analyses demonstrated that the minor (C) allele of rs7697189 increased lung function to a greater extent in males than females (untransformed FEV1β = 0.028 [SE 0.0022] litres in males vs β = 0.009 [SE 0.0014] litres in females), and this effect was not accounted for by differential effects on height, smoking or age at puberty. This SNP resides upstream of the gene encoding hedgehog-interacting protein (HHIP) and has previously been reported for association with lung function andHHIPexpression in lung tissue. In our analyses, whileHHIPexpression in lung tissue was significantly different between the sexes with females having higher expression (most significant probeset P=6.90 × 10−6) after adjusting for age and smoking, rs7697189 did not demonstrate sex differential effects on expression. Establishing the mechanism by whichHHIPSNPs have different effects on lung function in males and females will be important for our understanding of lung health and diseases, such as chronic obstructive pulmonary disease (COPD), in both sexes.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2019-03-31 |