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Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo.
Tuesday,2012-11-06 12:25 America/Los_Angeles — eenright
| Title | Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo. |
| Publication Type | Journal Article |
| Year of Publication | 2010 |
| Authors | M Ikram, K, Sim, X, Xueling, S, Jensen, RA, Cotch, MFrances, Hewitt, AW, Ikram, AM, Wang, JJin, Klein, R, Klein, BEK, Breteler, MMB, Cheung, N, Liew, G, Mitchell, P, Uitterlinden, AG, Rivadeneira, F, Hofman, A, de Jong, PTVM, van Duijn, CM, Kao, L, Cheng, C-Y, Smith, AVernon, Glazer, NL, Lumley, T, McKnight, B, Psaty, BM, Jonasson, F, Eiriksdottir, G, Aspelund, T, Harris, TB, Launer, LJ, Taylor, KD, Li, X, Iyengar, SK, Xi, Q, Sivakumaran, TA, Mackey, DA, Macgregor, S, Martin, NG, Young, TL, Bis, JC, Wiggins, KL, Heckbert, SR, Hammond, CJ, Andrew, T, Fahy, S, Attia, J, Holliday, EG, Scott, RJ, Islam, FMAmirul, Rotter, JI, McAuley, AK, Boerwinkle, E, Tai, SE, Gudnason, V, Siscovick, DS, Vingerling, JR, Wong, TY |
| Corporate/Institutional Authors | Global BPgen Consortium |
| Journal | PLoS Genet |
| Volume | 6 |
| Issue | 10 |
| Pagination | e1001184 |
| Date Published | 2010 Oct 28 |
| ISSN | 1553-7404 |
| Keywords | Adolescent, Adult, Aged, Aged, 80 and over, Cardiovascular Diseases, Child, Child, Preschool, Chromosomes, Human, Pair 12, Chromosomes, Human, Pair 19, Chromosomes, Human, Pair 5, Chromosomes, Human, Pair 6, Cohort Studies, European Continental Ancestry Group, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Meta-Analysis as Topic, Microcirculation, Middle Aged, Polymorphism, Single Nucleotide, Retinal Vessels, Young Adult |
| Abstract | <p>There 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.</p> |
| DOI | 10.1371/journal.pgen.1001184 |
| Alternate Journal | PLoS Genet. |
| PubMed ID | 21060863 |
| PubMed Central ID | PMC2965750 |
| Grant List | N01HC55020 / HL / NHLBI NIH HHS / United States UL1RR025005 / RR / NCRR NIH HHS / United States T32 HL007902 / HL / NHLBI NIH HHS / United States ZIA EY000401-09 / / Intramural NIH HHS / United States ZIA EY000401-13 / / Intramural NIH HHS / United States G0801056 / / Medical Research Council / United Kingdom N01AG12100 / AG / NIA NIH HHS / United States N01HC55018 / HL / NHLBI NIH HHS / United States Z01 EY000426-05 / / Intramural NIH HHS / United States MC_UP_A100_1003 / / Medical Research Council / United Kingdom R01 EY018246 / EY / NEI NIH HHS / United States Z99 EY999999 / / Intramural NIH HHS / United States UL1 RR025005 / RR / NCRR NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States ZIA EY000401-11 / / Intramural NIH HHS / United States ZIA EY000403-13 / / Intramural NIH HHS / United States ZIA EY000426-10 / / Intramural NIH HHS / United States N01-HC-55022 / HC / NHLBI NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States M01 RR000069 / RR / NCRR NIH HHS / United States N01-HC-55016 / HC / NHLBI NIH HHS / United States ZIA EY000426-13 / / Intramural NIH HHS / United States ZIA EY000403-14 / / Intramural NIH HHS / United States ZIA EY000426-08 / / Intramural NIH HHS / United States ZIA EY000401-08 / / Intramural NIH HHS / United States MC_U105630924 / / Medical Research Council / United Kingdom R01 HL087652 / HL / NHLBI NIH HHS / United States U01 HG004402 / HG / NHGRI NIH HHS / United States T32HL007902 / HL / NHLBI NIH HHS / United States N01HC55022 / HL / NHLBI NIH HHS / United States ZIA EY000403-11 / / Intramural NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01-HC-55021 / HC / NHLBI NIH HHS / United States ZIA EY000401-12 / / Intramural NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01HC55015 / HL / NHLBI NIH HHS / United States Z01 EY000426-04 / / Intramural NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States U01HG004402 / HG / NHGRI NIH HHS / United States N01HC-55222 / HC / NHLBI NIH HHS / United States ZIA EY000426-11 / / Intramural NIH HHS / United States ZIA EY000403-10 / / Intramural NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States N01-HC-55019 / HC / NHLBI NIH HHS / United States Z01 EY000426 / EY / NEI NIH HHS / United States R01HL087641 / HL / NHLBI NIH HHS / United States N01-HC-55015 / HC / NHLBI NIH HHS / United States ZIA EY000403-09 / / Intramural NIH HHS / United States G0401527 / / Medical Research Council / United Kingdom G0701863 / / Medical Research Council / United Kingdom Z01 EY000403-06 / / Intramural NIH HHS / United States M01RR00069 / RR / NCRR NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States ZIA EY000403-08 / / Intramural NIH HHS / United States N01-HC-55020 / HC / NHLBI NIH HHS / United States N01HC55016 / HL / NHLBI NIH HHS / United States ZIA EY000401-15 / / Intramural NIH HHS / United States Z01 EY000403-07 / / Intramural NIH HHS / United States Z01 EY000401 / EY / NEI NIH HHS / United States Z01 EY000401-06 / / Intramural NIH HHS / United States ZIA EY000426-09 / / Intramural NIH HHS / United States ZIA EY000426-07 / / Intramural NIH HHS / United States N01HC55019 / HL / NHLBI NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States ZIA EY000426-12 / / Intramural NIH HHS / United States DK063491 / DK / NIDDK NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States ZIA EY000426-06 / / Intramural NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01-HC-55018 / HC / NHLBI NIH HHS / United States ZIA EY000403-15 / / Intramural NIH HHS / United States N01HC55021 / HL / NHLBI NIH HHS / United States R01 HL087641 / HL / NHLBI NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States Z01 AG007380 / AG / NIA NIH HHS / United States ZIA EY000401-14 / / Intramural NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States Z01 EY000401-07 / / Intramural NIH HHS / United States ZIA EY000401-10 / / Intramural NIH HHS / United States ZIA EY000403-12 / / Intramural NIH HHS / United States |