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Article: Four novel loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation In vivo

TitleFour novel loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation In vivo
Authors
Issue Date2010
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosgenetics.org/
Citation
PLoS Genetics, 2010, v. 6 n. 10, article number e1001184 How to Cite?
AbstractThere is increasing evidence that the microcirculation plays an important role in the pathogenesis of cardiovascular diseases. Changes in retinal vascular caliber reflect early microvascular disease and predict incident cardiovascular events. We performed a genome-wide association study to identify genetic variants associated with retinal vascular caliber. We analyzed data from four population-based discovery cohorts with 15,358 unrelated Caucasian individuals, who are members of the Cohort for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and replicated findings in four independent Caucasian cohorts (n = 6,652). All participants had retinal photography and retinal arteriolar and venular caliber measured from computer software. In the discovery cohorts, 179 single nucleotide polymorphisms (SNP) spread across five loci were significantly associated (p<5.0×10-8) with retinal venular caliber, but none showed association with arteriolar caliber. Collectively, these five loci explain 1.0%-3.2% of the variation in retinal venular caliber. Four out of these five loci were confirmed in independent replication samples. In the combined analyses, the top SNPs at each locus were: rs2287921 (19q13; p = 1.61×10-25, within the RASIP1 locus), rs225717 (6q24; p = 1.25×10-16, adjacent to the VTA1 and NMBR loci), rs10774625 (12q24; p = 2.15×10-13, in the region of ATXN2,SH2B3 and PTPN11 loci), and rs17421627 (5q14; p = 7.32×10-16, adjacent to the MEF2C locus). In two independent samples, locus 12q24 was also associated with coronary heart disease and hypertension. Our population-based genome-wide association study demonstrates four novel loci associated with retinal venular caliber, an endophenotype of the microcirculation associated with clinical cardiovascular disease. These data provide further insights into the contribution and biological mechanisms of microcirculatory changes that underlie cardiovascular disease.
Persistent Identifierhttp://hdl.handle.net/10722/183600
ISSN
2014 Impact Factor: 7.528
2015 SCImago Journal Rankings: 6.308
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorKamran Ikram, Men_US
dc.contributor.authorXueling, Sen_US
dc.contributor.authorJensen, RAen_US
dc.contributor.authorCotch, MFen_US
dc.contributor.authorHewitt, AWen_US
dc.contributor.authorIkram, MAen_US
dc.contributor.authorWang, JJen_US
dc.contributor.authorKlein, Ren_US
dc.contributor.authorKlein, BEKen_US
dc.contributor.authorBreteler, MMBen_US
dc.contributor.authorCheung, Nen_US
dc.contributor.authorLiew, Gen_US
dc.contributor.authorMitchell, Pen_US
dc.contributor.authorUitterlinden, AGen_US
dc.contributor.authorRivadeneira, Fen_US
dc.contributor.authorHofman, Aen_US
dc.contributor.authorDe Jong, PTVMen_US
dc.contributor.authorVan Duijn, CMen_US
dc.contributor.authorKao, Len_US
dc.contributor.authorCheng, CYen_US
dc.contributor.authorSmith, AVen_US
dc.contributor.authorGlazer, NLen_US
dc.contributor.authorLumley, Ten_US
dc.contributor.authorMcknight, Ben_US
dc.contributor.authorPsaty, BMen_US
dc.contributor.authorJonasson, Fen_US
dc.contributor.authorEiriksdottir, Gen_US
dc.contributor.authorAspelund, Ten_US
dc.contributor.authorHarris, TBen_US
dc.contributor.authorLauner, LJen_US
dc.contributor.authorTaylor, KDen_US
dc.contributor.authorLi, Xen_US
dc.contributor.authorIyengar, SKen_US
dc.contributor.authorXi, Qen_US
dc.contributor.authorSivakumaran, TAen_US
dc.contributor.authorMackey, DAen_US
dc.contributor.authorMacgregor, Sen_US
dc.contributor.authorMartin, NGen_US
dc.contributor.authorYoung, TLen_US
dc.contributor.authorBis, JCen_US
dc.contributor.authorWiggins, KLen_US
dc.contributor.authorHeckbert, SRen_US
dc.contributor.authorHammond, CJen_US
dc.contributor.authorAndrew, Ten_US
dc.contributor.authorFahy, Sen_US
dc.contributor.authorAttia, Jen_US
dc.contributor.authorHolliday, EGen_US
dc.contributor.authorScott, RJen_US
dc.contributor.authorIslam, FMAen_US
dc.contributor.authorRotter, JIen_US
dc.contributor.authorMcauley, AKen_US
dc.contributor.authorBoerwinkle, Een_US
dc.contributor.authorTai, ESen_US
dc.contributor.authorGudnason, Ven_US
dc.contributor.authorSiscovick, DSen_US
dc.contributor.authorVingerling, JRen_US
dc.contributor.authorWong, TYen_US
dc.date.accessioned2013-05-28T06:15:15Z-
dc.date.available2013-05-28T06:15:15Z-
dc.date.issued2010en_US
dc.identifier.citationPLoS Genetics, 2010, v. 6 n. 10, article number e1001184en_US
dc.identifier.issn1553-7390en_US
dc.identifier.urihttp://hdl.handle.net/10722/183600-
dc.description.abstractThere is increasing evidence that the microcirculation plays an important role in the pathogenesis of cardiovascular diseases. Changes in retinal vascular caliber reflect early microvascular disease and predict incident cardiovascular events. We performed a genome-wide association study to identify genetic variants associated with retinal vascular caliber. We analyzed data from four population-based discovery cohorts with 15,358 unrelated Caucasian individuals, who are members of the Cohort for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and replicated findings in four independent Caucasian cohorts (n = 6,652). All participants had retinal photography and retinal arteriolar and venular caliber measured from computer software. In the discovery cohorts, 179 single nucleotide polymorphisms (SNP) spread across five loci were significantly associated (p<5.0×10-8) with retinal venular caliber, but none showed association with arteriolar caliber. Collectively, these five loci explain 1.0%-3.2% of the variation in retinal venular caliber. Four out of these five loci were confirmed in independent replication samples. In the combined analyses, the top SNPs at each locus were: rs2287921 (19q13; p = 1.61×10-25, within the RASIP1 locus), rs225717 (6q24; p = 1.25×10-16, adjacent to the VTA1 and NMBR loci), rs10774625 (12q24; p = 2.15×10-13, in the region of ATXN2,SH2B3 and PTPN11 loci), and rs17421627 (5q14; p = 7.32×10-16, adjacent to the MEF2C locus). In two independent samples, locus 12q24 was also associated with coronary heart disease and hypertension. Our population-based genome-wide association study demonstrates four novel loci associated with retinal venular caliber, an endophenotype of the microcirculation associated with clinical cardiovascular disease. These data provide further insights into the contribution and biological mechanisms of microcirculatory changes that underlie cardiovascular disease.en_US
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosgenetics.org/en_US
dc.relation.ispartofPLoS Geneticsen_US
dc.titleFour novel loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation In vivoen_US
dc.typeArticleen_US
dc.identifier.emailCheung, N: dannycheung@hotmail.comen_US
dc.identifier.emailLauner, LJ: dannycheung@hotmail.comen_US
dc.identifier.authorityCheung, N=rp01752en_US
dc.identifier.authorityLauner, LJ=rp01752en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1371/journal.pgen.1001184en_US
dc.identifier.pmid21060863-
dc.identifier.scopuseid_2-s2.0-78449249315en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78449249315&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume6en_US
dc.identifier.issue10en_US
dc.identifier.spagearticle number e1001184en_US
dc.identifier.epagearticle number e1001184en_US
dc.identifier.isiWOS:000283647800015-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridKamran Ikram, M=55196332300en_US
dc.identifier.scopusauthoridXueling, S=6506715419en_US
dc.identifier.scopusauthoridJensen, RA=7403518139en_US
dc.identifier.scopusauthoridCotch, MF=6603036992en_US
dc.identifier.scopusauthoridHewitt, AW=12142162700en_US
dc.identifier.scopusauthoridIkram, MA=15062786500en_US
dc.identifier.scopusauthoridWang, JJ=35231432000en_US
dc.identifier.scopusauthoridKlein, R=35232138400en_US
dc.identifier.scopusauthoridKlein, BEK=35433541400en_US
dc.identifier.scopusauthoridBreteler, MMB=7101734115en_US
dc.identifier.scopusauthoridCheung, N=8054683900en_US
dc.identifier.scopusauthoridLiew, G=12796147900en_US
dc.identifier.scopusauthoridMitchell, P=7402933815en_US
dc.identifier.scopusauthoridUitterlinden, AG=35231615000en_US
dc.identifier.scopusauthoridRivadeneira, F=7801419664en_US
dc.identifier.scopusauthoridHofman, A=36048731400en_US
dc.identifier.scopusauthoridde Jong, PTVM=7402785120en_US
dc.identifier.scopusauthoridvan Duijn, CM=6603813300en_US
dc.identifier.scopusauthoridKao, L=7403531208en_US
dc.identifier.scopusauthoridCheng, CY=55196332300en_US
dc.identifier.scopusauthoridSmith, AV=6506715419en_US
dc.identifier.scopusauthoridGlazer, NL=7403518139en_US
dc.identifier.scopusauthoridLumley, T=6603036992en_US
dc.identifier.scopusauthoridMcKnight, B=12142162700en_US
dc.identifier.scopusauthoridPsaty, BM=15062786500en_US
dc.identifier.scopusauthoridJonasson, F=35231432000en_US
dc.identifier.scopusauthoridEiriksdottir, G=35232138400en_US
dc.identifier.scopusauthoridAspelund, T=35433541400en_US
dc.identifier.scopusauthoridHarris, TB=7101734115en_US
dc.identifier.scopusauthoridLauner, LJ=8054683900en_US
dc.identifier.scopusauthoridTaylor, KD=12796147900en_US
dc.identifier.scopusauthoridLi, X=7402933815en_US
dc.identifier.scopusauthoridIyengar, SK=35231615000en_US
dc.identifier.scopusauthoridXi, Q=7801419664en_US
dc.identifier.scopusauthoridSivakumaran, TA=36048731400en_US
dc.identifier.scopusauthoridMacKey, DA=7402785120en_US
dc.identifier.scopusauthoridMacGregor, S=36037246700en_US
dc.identifier.scopusauthoridMartin, NG=55031027900en_US
dc.identifier.scopusauthoridYoung, TL=28767473300en_US
dc.identifier.scopusauthoridBis, JC=7406753503en_US
dc.identifier.scopusauthoridWiggins, KL=8509316100en_US
dc.identifier.scopusauthoridHeckbert, SR=7003921176en_US
dc.identifier.scopusauthoridHammond, CJ=7006533169en_US
dc.identifier.scopusauthoridAndrew, T=35374213400en_US
dc.identifier.scopusauthoridFahy, S=7003807327en_US
dc.identifier.scopusauthoridAttia, J=6602165684en_US
dc.identifier.scopusauthoridHolliday, EG=8703984700en_US
dc.identifier.scopusauthoridScott, RJ=35375662400en_US
dc.identifier.scopusauthoridIslam, FMA=7006392362en_US
dc.identifier.scopusauthoridRotter, JI=7403523428en_US
dc.identifier.scopusauthoridMcAuley, AK=35210582200en_US
dc.identifier.scopusauthoridBoerwinkle, E=7202158111en_US
dc.identifier.scopusauthoridTai, ES=9942277700en_US
dc.identifier.scopusauthoridGudnason, V=6701811456en_US
dc.identifier.scopusauthoridSiscovick, DS=22958177700en_US
dc.identifier.scopusauthoridVingerling, JR=35234029100en_US
dc.identifier.scopusauthoridWong, TY=35376988300en_US

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