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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2007

Open Access 01-09-2007 | Research

Genome-wide association with select biomarker traits in the Framingham Heart Study

Authors: Emelia J Benjamin, Josée Dupuis, Martin G Larson, Kathryn L Lunetta, Sarah L Booth, Diddahally R Govindaraju, Sekar Kathiresan, John F Keaney Jr, Michelle J Keyes, Jing-Ping Lin, James B Meigs, Sander J Robins, Jian Rong, Renate Schnabel, Joseph A Vita, Thomas J Wang, Peter WF Wilson, Philip A Wolf, Ramachandran S Vasan

Published in: BMC Medical Genetics | Special Issue 1/2007

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Abstract

Background

Systemic biomarkers provide insights into disease pathogenesis, diagnosis, and risk stratification. Many systemic biomarker concentrations are heritable phenotypes. Genome-wide association studies (GWAS) provide mechanisms to investigate the genetic contributions to biomarker variability unconstrained by current knowledge of physiological relations.

Methods

We examined the association of Affymetrix 100K GeneChip single nucleotide polymorphisms (SNPs) to 22 systemic biomarker concentrations in 4 biological domains: inflammation/oxidative stress; natriuretic peptides; liver function; and vitamins. Related members of the Framingham Offspring cohort (n = 1012; mean age 59 ± 10 years, 51% women) had both phenotype and genotype data (minimum-maximum per phenotype n = 507–1008). We used Generalized Estimating Equations (GEE), Family Based Association Tests (FBAT) and variance components linkage to relate SNPs to multivariable-adjusted biomarker residuals. Autosomal SNPs (n = 70,987) meeting the following criteria were studied: minor allele frequency ≥ 10%, call rate ≥ 80% and Hardy-Weinberg equilibrium p ≥ 0.001.

Results

With GEE, 58 SNPs had p < 10-6: the top SNPs were rs2494250 (p = 1.00*10-14) and rs4128725 (p = 3.68*10-12) for monocyte chemoattractant protein-1 (MCP1), and rs2794520 (p = 2.83*10-8) and rs2808629 (p = 3.19*10-8) for C-reactive protein (CRP) averaged from 3 examinations (over about 20 years). With FBAT, 11 SNPs had p < 10-6: the top SNPs were the same for MCP1 (rs4128725, p = 3.28*10-8, and rs2494250, p = 3.55*10-8), and also included B-type natriuretic peptide (rs437021, p = 1.01*10-6) and Vitamin K percent undercarboxylated osteocalcin (rs2052028, p = 1.07*10-6). The peak LOD (logarithm of the odds) scores were for MCP1 (4.38, chromosome 1) and CRP (3.28, chromosome 1; previously described) concentrations; of note the 1.5 support interval included the MCP1 and CRP SNPs reported above (GEE model). Previous candidate SNP associations with circulating CRP concentrations were replicated at p < 0.05; the SNPs rs2794520 and rs2808629 are in linkage disequilibrium with previously reported SNPs. GEE, FBAT and linkage results are posted at http://​www.​ncbi.​nlm.​nih.​gov/​projects/​gap/​cgi-bin/​study.​cgi?​id=​phs000007.

Conclusion

The Framingham GWAS represents a resource to describe potentially novel genetic influences on systemic biomarker variability. The newly described associations will need to be replicated in other studies.
Literature
1.
Vasan RS: Biomarkers of cardiovascular disease: molecular basis and practical considerations. Circulation. 2006, 113: 2335-2362. 10.1161/CIRCULATIONAHA.104.482570.CrossRefPubMed
2.
3.
Blankenberg S, McQueen MJ, Smieja M, Pogue J, Balion C, Lonn E, Rupprecht HJ, Bickel C, Tiret L, Cambien F, Gerstein H, Munzel T, Yusuf S: Comparative impact of multiple biomarkers and N-Terminal pro-brain natriuretic peptide in the context of conventional risk factors for the prediction of recurrent cardiovascular events in the Heart Outcomes Prevention Evaluation (HOPE) Study. Circulation. 2006, 114: 201-208. 10.1161/CIRCULATIONAHA.105.590927.CrossRefPubMed
4.
Kistorp C, Raymond I, Pedersen F, Gustafsson F, Faber J, Hildebrandt P: N-terminal pro-brain natriuretic peptide, C-reactive protein, and urinary albumin levels as predictors of mortality and cardiovascular events in older adults. JAMA. 2005, 293: 1609-1616. 10.1001/jama.293.13.1609.CrossRefPubMed
5.
Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Omland T, Wolf PA, Vasan RS: Plasma natriuretic peptide levels and the risk of cardiovascular events and death. N Engl J Med. 2004, 350: 655-663. 10.1056/NEJMoa031994.CrossRefPubMed
6.
Wannamethee G, Ebrahim S, Shaper AG: Gamma-glutamyltransferase: determinants and association with mortality from ischemic heart disease and all causes. Am J Epidemiol. 1995, 142: 699-708.PubMed
7.
Lee DS, Evans JC, Robins SJ, Wilson PW, Albano I, Fox CS, Wang TJ, Benjamin EJ, D'Agostino RB, Vasan RS: Gamma glutamyl transferase and metabolic syndrome, cardiovascular disease, and mortality risk: the Framingham Heart Study. Arterioscler Thromb Vasc Biol. 2007, 27: 127-133. 10.1161/01.ATV.0000251993.20372.40.CrossRefPubMed
8.
Scragg R, Jackson R, Holdaway IM, Lim T, Beaglehole R: Myocardial infarction is inversely associated with plasma 25-hydroxyvitamin D3 levels: a community-based study. Int J Epidemiol. 1990, 19: 559-563. 10.1093/ije/19.3.559.CrossRefPubMed
9.
Ridker PM, Hennekens CH, Buring JE, Rifai N: C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000, 342: 836-843. 10.1056/NEJM200003233421202.CrossRefPubMed
10.
Danesh J, Collins R, Appleby P, Peto R: Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies. JAMA. 1998, 279: 1477-1482. 10.1001/jama.279.18.1477.CrossRefPubMed
11.
Kuller LH, Tracy RP, Shaten J, Meilahn EN, the MRFIT Research Group: Relation of C-reactive protein and coronary heart disease in the MRFIT nested case-control study. Am J Epidemiol. 1996, 144: 537-547.CrossRefPubMed
12.
Ridker PM, Hennekens CH, Roitman-Johnson B, Stampfer MJ, Allen J: Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy men. Lancet. 1998, 351: 88-92. 10.1016/S0140-6736(97)09032-6.CrossRefPubMed
13.
Harris TB, Ferrucci L, Tracy RP, Corti MC, Wacholder S, Ettinger WH, Heimovitz H, Cohen HJ, Wallace R: Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. Am J Med. 1999, 106: 506-512. 10.1016/S0002-9343(99)00066-2.CrossRefPubMed
14.
Dupuis J, Larson MG, Vasan RS, Massaro JM, Wilson PW, Lipinska I, Corey D, Vita JA, Keaney JF, Benjamin EJ: Genome scan of systemic biomarkers of vascular inflammation in the Framingham Heart Study: evidence for susceptibility loci on 1q. Atherosclerosis. 2005, 182: 307-314. 10.1016/j.atherosclerosis.2005.02.015.CrossRefPubMed
15.
Pankow JS, Folsom AR, Cushman M, Borecki IB, Hopkins PN, Eckfeldt JH, Tracy RP: Familial and genetic determinants of systemic markers of inflammation: the NHLBI family heart study. Atherosclerosis. 2001, 154: 681-689. 10.1016/S0021-9150(00)00586-4.CrossRefPubMed
16.
Wang TJ, Larson MG, Levy D, Benjamin EJ, Corey D, Leip EP, Vasan RS: Heritability and genetic linkage of plasma natriuretic peptide levels. Circulation. 2003, 108: 13-16. 10.1161/01.CIR.0000081657.83724.A7.CrossRefPubMed
17.
Bathum L, Petersen HC, Rosholm JU, Hyltoft PP, Vaupel J, Christensen K: Evidence for a substantial genetic influence on biochemical liver function tests: results from a population-based Danish twin study. Clin Chem. 2001, 47: 81-87.PubMed
18.
Pilia G, Chen WM, Scuteri A, Orru M, Albai G, Dei M, Lai S, Usala G, Lai M, Loi P, Mameli C, Vacca L, Deiana M, Olla N, Masala M, Cao A, Najjar SS, Terracciano A, Nedorezov T, Sharov A, Zonderman AB, Abecasis GR, Costa P, Lakatta E, Schlessinger D: Heritability of cardiovascular and personality traits in 6,148 Sardinians. PLoS Genet. 2006, 2: e132-10.1371/journal.pgen.0020132.PubMedCentralCrossRefPubMed
19.
Hunter D, De Lange M, Snieder H, MacGregor AJ, Swaminathan R, Thakker RV, Spector TD: Genetic contribution to bone metabolism, calcium excretion, and vitamin D and parathyroid hormone regulation. J Bone Miner Res. 2001, 16: 371-378. 10.1359/jbmr.2001.16.2.371.CrossRefPubMed
20.
Carlson CS, Aldred SF, Lee PK, Tracy RP, Schwartz SM, Rieder M, Liu K, Williams OD, Iribarren C, Lewis EC, Fornage M, Boerwinkle E, Gross M, Jaquish C, Nickerson DA, Myers RM, Siscovick DS, Reiner AP: Polymorphisms within the C-reactive protein (CRP) promoter region are associated with plasma CRP levels. Am J Hum Genet. 2005, 77: 64-77. 10.1086/431366.PubMedCentralCrossRefPubMed
21.
Cupples LA, Arruda HT, Benjamin EJ, D'Agostino RB, Demissie S, DeStefano AL, Dupuis J, Falls K, Fox CS, Gottlieb DJ, Govindaraju DR, Guo CY, Heard-Costa NL, Hwang SJ, Kathiresan S, Kiel DP, Laramie JM, Larson MG, Levy D, Liu CY, Lunetta KL, Mailman MD, Manning AK, Meigs JB, Murabito JM, Newton-Cheh C, O'Connor GT, O'Donnell CJ, Pandey MA, Seshadri S, Vasan RS, Wang ZY, Wilk JB, Wolf PA, Yang Q, Atwood LD: The Framingham Heart Study 100K SNP genome-wide association study resource: Overview of 17 phenotype working group reports. BMC Med Genet. 2007, 8 (Suppl 1): S1-PubMedCentralCrossRefPubMed
22.
Kannel WB, Feinleib M, McNamara PM, Garrison RJ, Castelli WP: An investigation of coronary heart disease in families. The Framingham offspring study. Am J Epidemiol. 1979, 110: 281-290.PubMed
23.
Vasan RS, Benjamin EJ, Larson MG, Leip EP, Wang TJ, Wilson PW, Levy D: Plasma natriuretic peptides for community screening for left ventricular hypertrophy and systolic dysfunction: the Framingham heart study. JAMA. 2002, 288: 1252-1259. 10.1001/jama.288.10.1252.CrossRefPubMed
24.
Walters MI, Gerarde HW: A microspectrophotometric method for the determination of bilirubin. Microchemical J. 1968, 13: 253-272. 10.1016/0026-265X(68)90015-5.CrossRef
25.
Djousse L, Levy D, Cupples LA, Evans JC, D'Agostino RB, Ellison RC: Total serum bilirubin and risk of cardiovascular disease in the Framingham offspring study. Am J Cardiol. 2001, 87: 1196-1200. 10.1016/S0002-9149(01)01494-1.CrossRefPubMed
26.
Roy AV: Rapid method for determining alkaline phosphatase activity in serum with thymolphthalein monophosphate. Clin Chem. 1970, 16: 431-436.PubMed
27.
Proksch GJ, Bonderman DP, Griep JA: AutoAnalyzer assay for serum alkaline phosphatase activity, with sodium thymolphthalein monophosphate as substrate. Clin Chem. 1973, 19: 103-105.PubMed
28.
Henry RJ, Chiamori N, Golub OJ, Berkman S: Revised spectrophotometric methods for the determination of glutamic-oxalacetic transaminase, glutamic-pyruvic transaminase, and lactic acid dehydrogenase. Am J Clin Pathol. 1960, 34: 381-398.PubMed
29.
Davidson KW, Sadowski JA: Determination of vitamin K compounds in plasma or serum by high-performance liquid chromatography using postcolumn chemical reduction and fluorimetric detection. Methods Enzymol. 1997, 282: 408-421.CrossRefPubMed
30.
Gundberg CM, Hauschka PV, Lian JB, Gallop PM: Osteocalcin: isolation, characterization, and detection. Methods Enzymol. 1984, 107: 516-544.CrossRefPubMed
31.
Gundberg CM, Nieman SD, Abrams S, Rosen H: Vitamin K status and bone health: an analysis of methods for determination of undercarboxylated osteocalcin. J Clin Endocrinol Metab. 1998, 83: 3258-3266. 10.1210/jc.83.9.3258.PubMed
32.
Kathiresan S, Larson MG, Vasan RS, Guo CY, Gona P, Keaney JF, Wilson PW, Newton-Cheh C, Musone SL, Camargo AL, Drake JA, Levy D, O'Donnell CJ, Hirschhorn JN, Benjamin EJ: Contribution of clinical correlates and 13 C-reactive protein gene polymorphisms to interindividual variability in serum C-reactive protein level. Circulation. 2006, 113: 1415-1423. 10.1161/CIRCULATIONAHA.105.591271.CrossRefPubMed
33.
Herbert A, Gerry NP, McQueen MB, Heid IM, Pfeufer A, Illig T, Wichmann HE, Meitinger T, Hunter D, Hu FB, Colditz G, Hinney A, Hebebrand J, Koberwitz K, Zhu X, Cooper R, Ardlie K, Lyon H, Hirschhorn JN, Laird NM, Lenburg ME, Lange C, Christman MF: A common genetic variant is associated with adult and childhood obesity. Science. 2006, 312: 279-283. 10.1126/science.1124779.CrossRefPubMed
34.
Abecasis GR, Cherny SS, Cookson WO, Cardon LR: Merlin – rapid analysis of dense genetic maps using sparse gene flow trees. Nat Genet. 2002, 30: 97-101. 10.1038/ng786.CrossRefPubMed
35.
36.
Nagelkerke NJD: A note on a general definition of the coefficient of determination. Biometrika. 1991, 78: 691-692. 10.1093/biomet/78.3.691.CrossRef
37.
Cockayne S, Adamson J, Lanham-New S, Shearer MJ, Gilbody S, Torgerson DJ: Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials. Arch Intern Med. 2006, 166: 1256-1261. 10.1001/archinte.166.12.1256.CrossRefPubMed
38.
Szulc P, Chapuy MC, Meunier PJ, Delmas PD: Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture in elderly women. J Clin Invest. 1993, 91: 1769-1774.PubMedCentralCrossRefPubMed
39.
Lin JP, Cupples LA, Wilson PW, Heard-Costa N, O'Donnell CJ: Evidence for a gene influencing serum bilirubin on chromosome 2q telomere: a genomewide scan in the Framingham study. Am J Hum Genet. 2003, 72: 1029-1034. 10.1086/373964.PubMedCentralCrossRefPubMed
40.
Lin JP, O'Donnell CJ, Schwaiger JP, Cupples LA, Lingenhel A, Hunt SC, Yang S, Kronenberg F: Association between the UGT1A1*28 allele, bilirubin levels, and coronary heart disease in the Framingham Heart Study. Circulation. 2006, 114: 1476-1481. 10.1161/CIRCULATIONAHA.106.633206.CrossRefPubMed
41.
Zee RY, Ridker PM: Polymorphism in the human C-reactive protein (CRP) gene, plasma concentrations of CRP, and the risk of future arterial thrombosis. Atherosclerosis. 2002, 162: 217-219. 10.1016/S0021-9150(01)00703-1.CrossRefPubMed
42.
Szalai AJ, McCrory MA, Cooper GS, Wu J, Kimberly RP: Association between baseline levels of C-reactive protein (CRP) and a dinucleotide repeat polymorphism in the intron of the CRP gene. Genes Immun. 2002, 3: 14-19. 10.1038/sj.gene.6363820.CrossRefPubMed
43.
Suk HJ, Ridker PM, Cook NR, Zee RY: Relation of polymorphism within the C-reactive protein gene and plasma CRP levels. Atherosclerosis. 2005, 178: 139-145. 10.1016/j.atherosclerosis.2004.07.033.CrossRefPubMed
44.
Davey SG, Lawlor DA, Harbord R, Timpson N, Rumley A, Lowe GD, Day IN, Ebrahim S: Association of C-reactive protein with blood pressure and hypertension: life course confounding and mendelian randomization tests of causality. Arterioscler Thromb Vasc Biol. 2005, 25: 1051-1056. 10.1161/01.ATV.0000160351.95181.d0.CrossRef
45.
Balistreri CR, Vasto S, Listi F, Grimaldi MP, Lio D, Colonna-Romano G, Caruso M, Caimi G, Hoffmann E, Caruso C, Candore G: Association between +1059G/C CRP polymorphism and acute myocardial infarction in a cohort of patients from Sicily: a pilot study. Ann N Y Acad Sci. 2006, 1067: 276-281. 10.1196/annals.1354.036.CrossRefPubMed
46.
Miller DT, Zee RY, Suk DJ, Kozlowski P, Chasman DI, Lazarus R, Cook NR, Ridker PM, Kwiatkowski DJ: Association of Common CRP Gene Variants with CRP Levels and Cardiovascular Events. Ann Hum Genet. 2005, 69: 623-638. 10.1111/j.1529-8817.2005.00210.x.CrossRefPubMed
47.
Eklund C, Lehtimaki T, Hurme M: Epistatic effect of C-reactive protein (CRP) single nucleotide polymorphism (SNP) +1059 and interleukin-1B SNP +3954 on CRP concentration in healthy male blood donors. Int J Immunogenet. 2005, 32: 229-232.CrossRefPubMed
48.
Szalai AJ, Wu J, Lange EM, McCrory MA, Langefeld CD, Williams A, Zakharkin SO, George V, Allison DB, Cooper GS, Xie F, Fan Z, Edberg JC, Kimberly RP: Single-nucleotide polymorphisms in the C-reactive protein (CRP) gene promoter that affect transcription factor binding, alter transcriptional activity, and associate with differences in baseline serum CRP level. J Mol Med. 2005, 83: 440-447. 10.1007/s00109-005-0658-0.CrossRefPubMed
49.
D'Aiuto F, Casas JP, Shah T, Humphries SE, Hingorani AD, Tonetti MS: C-reactive protein (+1444C>T) polymorphism influences CRP response following a moderate inflammatory stimulus. Atherosclerosis. 2005, 179: 413-417. 10.1016/j.atherosclerosis.2004.10.036.CrossRefPubMed
50.
Kovacs A, Green F, Hansson LO, Lundman P, Samnegard A, Boquist S, Ericsson CG, Watkins H, Hamsten A, Tornvall P: A novel common single nucleotide polymorphism in the promoter region of the C-reactive protein gene associated with the plasma concentration of C-reactive protein. Atherosclerosis. 2005, 178: 193-198. 10.1016/j.atherosclerosis.2004.08.018.CrossRefPubMed
51.
Register TC, Burdon KP, Lenchik L, Bowden DW, Hawkins GA, Nicklas BJ, Lohman K, Hsu FC, Langefeld CD, Carr JJ: Variability of serum soluble intercellular adhesion molecule-1 measurements attributable to a common polymorphism. Clin Chem. 2004, 50: 2185-2187. 10.1373/clinchem.2004.036806.CrossRefPubMed
52.
Puthothu B, Krueger M, Bernhardt M, Heinzmann A: ICAM1 amino-acid variant K469E is associated with paediatric bronchial asthma and elevated sICAM1 levels. Genes Immun. 2006, 7: 322-326. 10.1038/sj.gene.6364302.CrossRefPubMed
53.
Kronig H, Riedel M, Schwarz MJ, Strassnig M, Moller HJ, Ackenheil M, Muller N: ICAM G241A polymorphism and soluble ICAM-1 serum levels: evidence for an active immune process in schizophrenia. Neuroimmunomodulation. 2005, 12: 54-59. 10.1159/000082364.CrossRefPubMed
54.
Ponthieux A, Lambert D, Herbeth B, Droesch S, Pfister M, Visvikis S: Association between Gly241Arg ICAM-1 gene polymorphism and serum sICAM-1 concentration in the Stanislas cohort. Eur J Hum Genet. 2003, 11: 679-686. 10.1038/sj.ejhg.5201033.CrossRefPubMed
55.
Brull DJ, Montgomery HE, Sanders J, Dhamrait S, Luong L, Rumley A, Lowe GD, Humphries SE: Interleukin-6 gene -174g>c and -572g>c promoter polymorphisms are strong predictors of plasma interleukin-6 levels after coronary artery bypass surgery. Arterioscler Thromb Vasc Biol. 2001, 21: 1458-1463.CrossRefPubMed
56.
Boiardi L, Casali B, Farnetti E, Pipitone N, Nicoli D, Cantini F, Macchioni P, Bajocchi G, Catanoso MG, Pulsatelli L, Consonni D, Salvarani C: Relationship between interleukin 6 promoter polymorphism at position -174, IL-6 serum levels, and the risk of relapse/recurrence in polymyalgia rheumatica. J Rheumatol. 2006, 33: 703-708.PubMed
57.
Liu Y, Berthier-Schaad Y, Fallin MD, Fink NE, Tracy RP, Klag MJ, Smith MW, Coresh J: IL-6 haplotypes, inflammation, and risk for cardiovascular disease in a multiethnic dialysis cohort. J Am Soc Nephrol. 2006, 17: 863-870. 10.1681/ASN.2005050465.CrossRefPubMed
58.
Libra M, Signorelli SS, Bevelacqua Y, Navolanic PM, Bevelacqua V, Polesel J, Talamini R, Stivala F, Mazzarino MC, Malaponte G: Analysis of G(-174)C IL-6 polymorphism and plasma concentrations of inflammatory markers in patients with type 2 diabetes and peripheral arterial disease. J Clin Pathol. 2006, 59: 211-215. 10.1136/jcp.2004.025452.PubMedCentralCrossRefPubMed
59.
Ravaglia G, Forti P, Maioli F, Chiappelli M, Dolzani P, Martelli M, Bianchin M, Mariani E, Bolondi L, Licastro F: Associations of the -174 G/C interleukin-6 gene promoter polymorphism with serum interleukin 6 and mortality in the elderly. Biogerontology. 2005, 6: 415-423. 10.1007/s10522-005-4908-x.CrossRefPubMed
60.
Cardellini M, Perego L, D'Adamo M, Marini MA, Procopio C, Hribal ML, Andreozzi F, Frontoni S, Giacomelli M, Paganelli M, Pontiroli AE, Lauro R, Folli F, Sesti G: C-174G polymorphism in the promoter of the interleukin-6 gene is associated with insulin resistance. Diabetes Care. 2005, 28: 2007-2012. 10.2337/diacare.28.8.2007.CrossRefPubMed
61.
Barbieri M, Rizzo MR, Papa M, Acampora R, De Angelis L, Olivieri F, Marchegiani F, Franceschi C, Paolisso G: Role of interaction between variants in the PPARG and interleukin-6 genes on obesity related metabolic risk factors. Exp Gerontol. 2005, 40: 599-604. 10.1016/j.exger.2005.05.004.CrossRefPubMed
62.
Haddy N, Sass C, Maumus S, Marie B, Droesch S, Siest G, Lambert D, Visvikis S: Biological variations, genetic polymorphisms and familial resemblance of TNF-alpha and IL-6 concentrations: STANISLAS cohort. Eur J Hum Genet. 2005, 13: 109-117. 10.1038/sj.ejhg.5201294.CrossRefPubMed
63.
McDermott DH, Yang Q, Kathiresan S, Cupples LA, Massaro JM, Keaney JF, Larson MG, Vasan RS, Hirschhorn JN, O'Donnell CJ, Murphy PM, Benjamin EJ: CCL2 polymorphisms are associated with serum monocyte chemoattractant protein-1 levels and myocardial infarction in the Framingham Heart Study. Circulation. 2005, 112: 1113-1120. 10.1161/CIRCULATIONAHA.105.543579.CrossRefPubMed
64.
Joven J, Coll B, Tous M, Ferre N, Alonso-Villaverde C, Parra S, Camps J: The influence of HIV infection on the correlation between plasma concentrations of monocyte chemoattractant protein-1 and carotid atherosclerosis. Clin Chim Acta. 2006, 368: 114-119. 10.1016/j.cca.2005.12.014.CrossRefPubMed
65.
Cheung VG, Spielman RS, Ewens KG, Weber TM, Morley M, Burdick JT: Mapping determinants of human gene expression by regional and genome-wide association. Nature. 2005, 437: 1365-1369. 10.1038/nature04244.PubMedCentralCrossRefPubMed
66.
Eglite S, Morin JM, Metzger H: Synthesis and secretion of monocyte chemotactic protein-1 stimulated by the high affinity receptor for IgE. J Immunol. 2003, 170: 2680-2687.CrossRefPubMed
67.
Gonzalez-Espinosa C, Odom S, Olivera A, Hobson JP, Martinez ME, Oliveira-Dos-Santos A, Barra L, Spiegel S, Penninger JM, Rivera J: Preferential signaling and induction of allergy-promoting lymphokines upon weak stimulation of the high affinity IgE receptor on mast cells. J Exp Med. 2003, 197: 1453-1465. 10.1084/jem.20021806.PubMedCentralCrossRefPubMed
68.
Malo JL, L'Archeveque J, Lummus Z, Bernstein D: Changes in specific IgE and IgG and monocyte chemoattractant protein-1 in workers with occupational asthma caused by diisocyanates and removed from exposure. J Allergy Clin Immunol. 2006, 118: 530-533. 10.1016/j.jaci.2006.04.022.CrossRefPubMed
69.
Bernstein DI, Cartier A, Cote J, Malo JL, Boulet LP, Wanner M, Milot J, L'Archeveque J, Trudeau C, Lummus Z: Diisocyanate antigen-stimulated monocyte chemoattractant protein-1 synthesis has greater test efficiency than specific antibodies for identification of diisocyanate asthma. Am J Respir Crit Care Med. 2002, 166: 445-450. 10.1164/rccm.2109018.CrossRefPubMed
70.
Baghestanian M, Hofbauer R, Kiener HP, Bankl HC, Wimazal F, Willheim M, Scheiner O, Fureder W, Muller MR, Bevec D, Lechner K, Valent P: The c-kit ligand stem cell factor and anti-IgE promote expression of monocyte chemoattractant protein-1 in human lung mast cells. Blood. 1997, 90: 4438-4449.PubMed
71.
Matsuda K, Piliponsky AM, Iikura M, Nakae S, Wang EW, Dutta SM, Kawakami T, Tsai M, Galli SJ: Monomeric IgE enhances human mast cell chemokine production: IL-4 augments and dexamethasone suppresses the response. J Allergy Clin Immunol. 2005, 116: 1357-1363. 10.1016/j.jaci.2005.08.042.CrossRefPubMed
72.
Gosset P, Tillie-Leblond I, Oudin S, Parmentier O, Wallaert B, Joseph M, Tonnel AB: Production of chemokines and proinflammatory and antiinflammatory cytokines by human alveolar macrophages activated by IgE receptors. J Allergy Clin Immunol. 1999, 103: 289-297. 10.1016/S0091-6749(99)70504-X.CrossRefPubMed
73.
Lohmueller KE, Pearce CL, Pike M, Lander ES, Hirschhorn JN: Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nat Genet. 2003, 33: 177-182. 10.1038/ng1071.CrossRefPubMed
74.
Hegele RA: SNP judgments and freedom of association. Arterioscler Thromb Vasc Biol. 2002, 22: 1058-1061. 10.1161/01.ATV.0000026801.56080.14.CrossRefPubMed
Metadata
Title
Genome-wide association with select biomarker traits in the Framingham Heart Study
Authors
Emelia J Benjamin
Josée Dupuis
Martin G Larson
Kathryn L Lunetta
Sarah L Booth
Diddahally R Govindaraju
Sekar Kathiresan
John F Keaney Jr
Michelle J Keyes
Jing-Ping Lin
James B Meigs
Sander J Robins
Jian Rong
Renate Schnabel
Joseph A Vita
Thomas J Wang
Peter WF Wilson
Philip A Wolf
Ramachandran S Vasan
Publication date
01-09-2007
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue Special Issue 1/2007
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/1471-2350-8-S1-S11

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