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dc.contributor.authorPrins, Bram
dc.contributor.authorKuchenbaecker, Karoline B
dc.contributor.authorBao, Yanchun
dc.contributor.authorSmart, Melissa
dc.contributor.authorZabaneh, Delilah
dc.contributor.authorFatemifar, Ghazaleh
dc.contributor.authorLuan, Jian'an
dc.contributor.authorWareham, Nicholas
dc.contributor.authorScott, Robert A
dc.contributor.authorPerry, John
dc.contributor.authorLangenberg, Claudia
dc.contributor.authorBenzeval, Michaela
dc.contributor.authorKumari, Meena
dc.contributor.authorZeggini, Eleftheria
dc.date.accessioned2017-12-12T16:08:52Z
dc.date.available2017-12-12T16:08:52Z
dc.date.issued2017-09-08
dc.identifier.issn2045-2322
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/270166
dc.description.abstractSerum biomarker levels are associated with the risk of complex diseases. Here, we aimed to gain insights into the genetic architecture of biomarker traits which can reflect health status. We performed genome-wide association analyses for twenty serum biomarkers involved in organ function and reproductive health. 9,961 individuals from the UK Household Longitudinal Study were genotyped using the Illumina HumanCoreExome array and variants imputed to the 1000 Genomes Project and UK10K haplotypes. We establish a polygenic heritability for all biomarkers, confirm associations of fifty-four established loci, and identify five novel, replicating associations at genome-wide significance. A low-frequency variant, rs28929474, (beta = 0.04, P = 2 × 10-10) was associated with levels of alanine transaminase, an indicator of liver damage. The variant is located in the gene encoding serine protease inhibitor, low levels of which are associated with alpha-1 antitrypsin deficiency which leads to liver disease. We identified novel associations (rs78900934, beta = 0.05, P = 6 × 10-12; rs2911280, beta = 0.09, P = 6 × 10-10) for dihydroepiandrosterone sulphate, a precursor to major sex-hormones, and for glycated haemoglobin (rs12819124, beta = -0.03, P = 4 × 10-9; rs761772, beta = 0.05, P = 5 × 10-9). rs12819124 is nominally associated with risk of type 2 diabetes. Our study offers insights into the genetic architecture of well-known and less well-studied biomarkers.
dc.description.sponsorshipPlease visit the publisher's website for further information.
dc.languageeng
dc.publisherSpringer Nature
dc.rightsAttribution 4.0 International
dc.rightsAttribution 4.0 International
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleGenome-wide analysis of health-related biomarkers in the UK Household Longitudinal Study reveals novel associations
dc.typeArticle
prism.issueIdentifier1
prism.number11008
prism.publicationDate2017
prism.publicationNameScientific Reports
prism.volume7
dc.identifier.doi10.17863/CAM.17000
dcterms.dateAccepted2017-08-08
rioxxterms.versionofrecord10.1038/s41598-017-10812-1
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.licenseref.startdate2017-09-08
dc.contributor.orcidLuan, Jian'an [0000-0003-3137-6337]
dc.contributor.orcidWareham, Nicholas [0000-0003-1422-2993]
dc.contributor.orcidPerry, John [0000-0001-6483-3771]
dc.contributor.orcidLangenberg, Claudia [0000-0002-5017-7344]
dc.identifier.eissn2045-2322
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMRC (MC_PC_13046)
pubs.funder-project-idMedical Research Council (MC_UU_12015/1)
pubs.funder-project-idMedical Research Council (MC_UU_12015/2)
pubs.funder-project-idMedical Research Council (MC_U106179471)
cam.issuedOnline2017-09-08


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