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dc.contributor.authorFranceschini N
dc.contributor.authorvan Rooij FJ
dc.contributor.authorPrins BP
dc.contributor.authorFeitosa MF
dc.contributor.authorKarakas M
dc.contributor.authorEckfeldt JH
dc.contributor.authorFolsom AR
dc.contributor.authorKopp J
dc.contributor.authorVaez A
dc.contributor.authorAndrews JS
dc.contributor.authorBaumert J
dc.contributor.authorBoraska V
dc.contributor.authorBroer L
dc.contributor.authorHayward C
dc.contributor.authorNgwa JS
dc.contributor.authorOkada Y
dc.contributor.authorPolasek O
dc.contributor.authorWestra HJ
dc.contributor.authorWang YA
dc.contributor.authorDel Greco M F
dc.contributor.authorGlazer NL
dc.contributor.authorKapur K
dc.contributor.authorKema IP
dc.contributor.authorLopez LM
dc.contributor.authorSchillert A
dc.contributor.authorSmith AV
dc.contributor.authorWinkler CA
dc.contributor.authorZgaga L
dc.contributor.authorLifeLines Cohort Study
dc.contributor.authorBandinelli S
dc.contributor.authorBergmann S
dc.contributor.authorBoban M
dc.contributor.authorBochud M
dc.contributor.authorChen YD
dc.contributor.authorDavies G
dc.contributor.authorDehghan A
dc.contributor.authorDing J
dc.contributor.authorDoering A
dc.contributor.authorDurda JP
dc.contributor.authorFerrucci L
dc.contributor.authorFranco OH
dc.contributor.authorFranke L
dc.contributor.authorGunjaca G
dc.contributor.authorHofman A
dc.contributor.authorHsu FC
dc.contributor.authorKolcic I
dc.contributor.authorKraja A
dc.contributor.authorKubo M
dc.contributor.authorLackner KJ
dc.contributor.authorLauner L
dc.contributor.authorLoehr LR
dc.contributor.authorLi G
dc.contributor.authorMeisinger C
dc.contributor.authorNakamura Y
dc.contributor.authorSchwienbacher C
dc.contributor.authorStarr JM
dc.contributor.authorTakahashi A
dc.contributor.authorTorlak V
dc.contributor.authorUitterlinden AG
dc.contributor.authorVitart V
dc.contributor.authorWaldenberger M
dc.contributor.authorWild PS
dc.contributor.authorKirin M
dc.contributor.authorZeller T
dc.contributor.authorZemunik T
dc.contributor.authorZhang Q
dc.contributor.authorZiegler A
dc.contributor.authorBlankenberg S
dc.contributor.authorBoerwinkle E
dc.contributor.authorBorecki IB
dc.contributor.authorCampbell H
dc.contributor.authorDeary IJ
dc.contributor.authorFrayling TM
dc.contributor.authorGieger C
dc.contributor.authorHarris TB
dc.contributor.authorHicks AA
dc.contributor.authorKoenig W
dc.contributor.authorO' Donnell CJ
dc.contributor.authorFox CS
dc.contributor.authorPramstaller PP
dc.contributor.authorPsaty BM
dc.contributor.authorReiner AP
dc.contributor.authorRotter JI
dc.contributor.authorRudan I
dc.contributor.authorSnieder H
dc.contributor.authorTanaka T
dc.contributor.authorvan Duijn CM
dc.contributor.authorVollenweider P
dc.contributor.authorWaeber G
dc.contributor.authorWilson JF
dc.contributor.authorWitteman JC
dc.contributor.authorWolffenbuttel BH
dc.contributor.authorWright AF
dc.contributor.authorWu Q
dc.contributor.authorLiu Y
dc.contributor.authorJenny NS
dc.contributor.authorNorth KE
dc.contributor.authorFelix JF
dc.contributor.authorAlizadeh BZ
dc.contributor.authorCupples LA
dc.contributor.authorPerry JR
dc.contributor.authorMorris AP
dc.date.accessioned2018-10-30T09:52:19Z
dc.date.available2018-10-30T09:52:19Z
dc.date.issued2012
dc.identifier.issn0002-9297
dc.identifier.urihttp://dx.doi.org/10.1016/j.ajhg.2012.08.021
dc.identifier.urihttp://hdl.handle.net/10863/6736
dc.description.abstractMany disorders are associated with altered serum protein concentrations, including malnutrition, cancer, and cardiovascular, kidney, and inflammatory diseases. Although these protein concentrations are highly heritable, relatively little is known about their underlying genetic determinants. Through transethnic meta-analysis of European-ancestry and Japanese genome-wide association studies, we identified six loci at genome-wide significance (p < 5 × 10(-8)) for serum albumin (HPN-SCN1B, GCKR-FNDC4, SERPINF2-WDR81, TNFRSF11A-ZCCHC2, FRMD5-WDR76, and RPS11-FCGRT, in up to 53,190 European-ancestry and 9,380 Japanese individuals) and three loci for total protein (TNFRS13B, 6q21.3, and ELL2, in up to 25,539 European-ancestry and 10,168 Japanese individuals). We observed little evidence of heterogeneity in allelic effects at these loci between groups of European and Japanese ancestry but obtained substantial improvements in the resolution of fine mapping of potential causal variants by leveraging transethnic differences in the distribution of linkage disequilibrium. We demonstrated a functional role for the most strongly associated serum albumin locus, HPN, for which Hpn knockout mice manifest low plasma albumin concentrations. Other loci associated with serum albumin harbor genes related to ribosome function, protein translation, and proteasomal degradation, whereas those associated with serum total protein include genes related to immune function. Our results highlight the advantages of transethnic meta-analysis for the discovery and fine mapping of complex trait loci and have provided initial insights into the underlying genetic architecture of serum protein concentrations and their association with human disease.en_US
dc.language.isoenen_US
dc.rights
dc.titleDiscovery and fine mapping of serum protein loci through transethnic meta-analysisen_US
dc.typeArticleen_US
dc.date.updated2018-10-30T08:41:46Z
dc.language.isiEN-GB
dc.journal.titleAmerican journal of human genetics
dc.description.fulltextnoneen_US


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