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

Open Access 01-09-2007 | Introduction

The Framingham Heart Study 100K SNP genome-wide association study resource: overview of 17 phenotype working group reports

Authors: L Adrienne Cupples, Heather T Arruda, Emelia J Benjamin, Ralph B D'Agostino Sr, Serkalem Demissie, Anita L DeStefano, Josée Dupuis, Kathleen M Falls, Caroline S Fox, Daniel J Gottlieb, Diddahally R Govindaraju, Chao-Yu Guo, Nancy L Heard-Costa, Shih-Jen Hwang, Sekar Kathiresan, Douglas P Kiel, Jason M Laramie, Martin G Larson, Daniel Levy, Chun-Yu Liu, Kathryn L Lunetta, Matthew D Mailman, Alisa K Manning, James B Meigs, Joanne M Murabito, Christopher Newton-Cheh, George T O'Connor, Christopher J O'Donnell, Mona Pandey, Sudha Seshadri, Ramachandran S Vasan, Zhen Y Wang, Jemma B Wilk, Philip A Wolf, Qiong Yang, Larry D Atwood

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

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Abstract

Background

The Framingham Heart Study (FHS), founded in 1948 to examine the epidemiology of cardiovascular disease, is among the most comprehensively characterized multi-generational studies in the world. Many collected phenotypes have substantial genetic contributors; yet most genetic determinants remain to be identified. Using single nucleotide polymorphisms (SNPs) from a 100K genome-wide scan, we examine the associations of common polymorphisms with phenotypic variation in this community-based cohort and provide a full-disclosure, web-based resource of results for future replication studies.

Methods

Adult participants (n = 1345) of the largest 310 pedigrees in the FHS, many biologically related, were genotyped with the 100K Affymetrix GeneChip. These genotypes were used to assess their contribution to 987 phenotypes collected in FHS over 56 years of follow up, including: cardiovascular risk factors and biomarkers; subclinical and clinical cardiovascular disease; cancer and longevity traits; and traits in pulmonary, sleep, neurology, renal, and bone domains. We conducted genome-wide variance components linkage and population-based and family-based association tests.

Results

The participants were white of European descent and from the FHS Original and Offspring Cohorts (examination 1 Offspring mean age 32 ± 9 years, 54% women). This overview summarizes the methods, selected findings and limitations of the results presented in the accompanying series of 17 manuscripts. The presented association results are based on 70,897 autosomal SNPs meeting the following criteria: minor allele frequency ≥ 10%, genotype call rate ≥ 80%, Hardy-Weinberg equilibrium p-value ≥ 0.001, and satisfying Mendelian consistency. Linkage analyses are based on 11,200 SNPs and short-tandem repeats. Results of phenotype-genotype linkages and associations for all autosomal SNPs are posted on the NCBI dbGaP website at http://​www.​ncbi.​nlm.​nih.​gov/​projects/​gap/​cgi-bin/​study.​cgi?​id=​phs000007.

Conclusion

We have created a full-disclosure resource of results, posted on the dbGaP website, from a genome-wide association study in the FHS. Because we used three analytical approaches to examine the association and linkage of 987 phenotypes with thousands of SNPs, our results must be considered hypothesis-generating and need to be replicated. Results from the FHS 100K project with NCBI web posting provides a resource for investigators to identify high priority findings for replication.
Appendix
Available only for authorised users
Literature
1.
Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, Haase N, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O'Donnell CJ, Roger V, Rumsfeld J, Sorlie P, Steinberger J, Thom T, Wasserthiel-Smoller S, Hong Y, American Heart Association Statistics Committee and Stroke Statistics Subcommittee: Heart disease and stroke statistics – 2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2007, 115 (5): e69-171. 10.1161/CIRCULATIONAHA.106.179918.CrossRefPubMed
2.
Myers RH, Kiely DK, Cupples LA, Kannel WB: Parental history is an independent risk factor for coronary artery disease: the Framingham Study. Am Heart J. 1990, 120 (4): 963-969. 10.1016/0002-8703(90)90216-K.CrossRefPubMed
3.
Lloyd-Jones DM, Nam BH, D'Agostino RB, Levy D, Murabito JM, Wang TJ, Wilson PWJ, O'Donnell CJ: Parental cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults: a prospective study of parents and offspring. JAMA. 2004, 291: 2204-2211. 10.1001/jama.291.18.2204.CrossRefPubMed
4.
Murabito JM, Pencina MJ, Nam BH, D'Agostino RB, Wang TJ, Lloyd-Jones D, Wilson PW, O'Donnell CJ: Sibling cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults. JAMA. 2005, 294: 3117-3123. 10.1001/jama.294.24.3117.CrossRefPubMed
5.
O'Donnell CJ, Chazaro I, Wilson PW, Fox C, Hannan MT, Kiel DP, Cupples LA: Evidence for heritability of abdominal aortic calcific deposits in the Framingham Heart Study. Circulation. 2002, 106 (3): 337-341. 10.1161/01.CIR.0000022663.26468.5B.CrossRefPubMed
6.
Fox CS, Polak JF, Chazaro I, Cupples A, Wolf PA, D'Agostino RA, O'Donnell CJ: Genetic and environmental contributions to atherosclerosis phenotypes in men and women: heritability of carotid intima-media thickness in the Framingham Heart Study. Stroke. 2003, 34 (2): 397-401. 10.1161/01.STR.0000048214.56981.6F.CrossRefPubMed
7.
Murabito JM, Guo C-Y, Fox CS, D'Agostino RB: Genetic Contributions to Peripheral Arterial Disease: Heritability of the Ankle-Brachial Blood Pressure Index in the Framingham Heart Study. Am J Epidemiol. 2006, 164 (10): 963-968. 10.1093/aje/kwj295.CrossRefPubMed
8.
Fox CS, Parise H, D'Agostino RB, Lloyd-Jones DM, Vasan RS, Wang TJ, Levy D, Wolf PA, Benjamin EJ: Parental atrial fibrillation as a risk factor for atrial fibrillation in offspring. JAMA. 2004, 291: 2851-2855. 10.1001/jama.291.23.2851.CrossRefPubMed
9.
Shearman AM, Cooper JA, Kotwinski PJ, Miller GJ, Humphries SE, Ardlie KG, Jordan B, Irenze K, Lunetta KL, Schuit SC, Uitterlinden AG, Pols HA, Demissie S, Cupples LA, Mendelsohn ME, Levy D, Housman DE: Estrogen receptor alpha gene variation is associated with risk of myocardial infarction in more than seven thousand men from five cohorts. Circ Res. 2006, 98 (5): 590-592. 10.1161/01.RES.0000210578.62102.a6.CrossRefPubMed
10.
Samani NJ, Burton P, Mangino M, Ball SG, Balmforth AJ, Barrett J, Bishop T, Hall A, BHF Family Heart Study Research Group: A genomewide linkage study of 1,933 families affected by premature coronary artery disease: The British Heart Foundation (BHF) Family Heart Study. Am J Hum Genet. 2005, 77 (6): 1011-1020. 10.1086/498653.CrossRefPubMed
11.
Wang L, Hauser ER, Shah SH, Pericak-Vance MA, Haynes C, Crosslin D, Harris M, Nelson S, Hale AB, Granger CB, Haines JL, Jones CJ, Crossman D, Seo D, Gregory SG, Kraus WE, Goldschmidt-Clermont PJ, Vance JM: Peakwide mapping on chromosome 3q13 identifies the kalirin gene as a novel candidate gene for coronary artery disease. Am J Hum Genet. 2007, 80 (4): 650-663. 10.1086/512981.PubMedCentralCrossRefPubMed
12.
Shearman AM, Cupples LA, Demissie S, Peter I, Schmid CH, Karas RH, Mendelsohn ME, Housman DE, Levy D: Association between estrogen receptor alpha gene variation and cardiovascular disease. Jama. 2003, 290 (17): 2263-2270. 10.1001/jama.290.17.2263.CrossRefPubMed
13.
Lahoz C, Schaefer EJ, Cupples LA, Wilson PW, Levy D, Osgood D, Parpos S, Pedro-Botet J, Daly JA, Ordovas JM: Apolipoprotein E genotype and cardiovascular disease in the Framingham Heart Study. Atherosclerosis. 2001, 154 (3): 529-537. 10.1016/S0021-9150(00)00570-0.CrossRefPubMed
14.
O'Donnell CJ, Lindpaintner K, Larson MG, Rao VS, Ordovas JM, Schaefer EJ, Myers RH, Levy D: Evidence for association and genetic linkage of the angiotensin-converting enzyme locus with hypertension and blood pressure in men but not women in the Framingham Heart Study. Circulation. 1998, 97 (18): 1766-1772.CrossRefPubMed
15.
Levy D, DeStefano AL, Larson MG, O'Donnell CJ, Lifton RP, Gavras H, Cupples LA, Myers RH: Evidence for a gene influencing blood pressure on chromosome 17. Genome scan linkage results for longitudinal blood pressure phenotypes in subjects from the framingham heart study. Hypertension. 2000, 36 (4): 477-483.CrossRefPubMed
16.
DeStefano AL, Larson MG, Mitchell GF, Benjamin EJ, Vasan RS, Li J, Corey D, Levy D: Genome-wide scan for pulse pressure in the National Heart, Lung and Blood Institute's Framingham Heart Study. Hypertension. 2004, 44 (2): 152-155. 10.1161/01.HYP.0000135248.62303.81.CrossRefPubMed
17.
Shearman AM, Ordovas JM, Cupples LA, Schaefer EJ, Harmon MD, Shao Y, Keen JD, DeStefano AL, Joost O, Wilson PW, Housman DE, Myers RH: Evidence for a gene influencing the TG/HDL-C ratio on chromosome 7q32.3-qter: a genome-wide scan in the Framingham study. Hum Mol Genet. 2000, 9 (9): 1315-1320. 10.1093/hmg/9.9.1315.CrossRefPubMed
18.
Lai CQ, Demissie S, Cupples LA, Zhu Y, Adiconis X, Parnell LD, Corella D, Ordovas JM: Influence of the APOA5 locus on plasma triglyceride, lipoprotein subclasses, and CVD risk in the Framingham Heart Study. J Lipid Res. 2004, 45 (11): 2096-2105. 10.1194/jlr.M400192-JLR200.CrossRefPubMed
19.
Yang Q, Lai CQ, Parnell L, Cupples LA, Adiconis X, Zhu Y, Wilson PW, Housman DE, Shearman AM, D'Agostino RB, Ordovas JM: Genome-wide linkage analyses and candidate gene fine mapping for HDL3 cholesterol: the Framingham Study. J Lipid Res. 2005, 46 (7): 1416-1425. 10.1194/jlr.M400382-JLR200.CrossRefPubMed
20.
Demissie S, Cupples LA, Shearman AM, Gruenthal KM, Peter I, Schmid CH, Karas RH, Housman DE, Mendelsohn ME, Ordovas JM: Estrogen receptor-alpha variants are associated with lipoprotein size distribution and particle levels in women: the Framingham Heart Study. Atherosclerosis. 2006, 185 (1): 210-218. 10.1016/j.atherosclerosis.2005.06.008.CrossRefPubMed
21.
Meigs JB, Cupples LA, Wilson PW: Parental transmission of type 2 diabetes: the Framingham Offspring Study. Diabetes. 2000, 49 (12): 2201-2207. 10.2337/diabetes.49.12.2201.CrossRefPubMed
22.
Meigs JB, Panhuysen CI, Myers RH, Wilson PW, Cupples LA: A genome-wide scan for loci linked to plasma levels of glucose and HbA(1c) in a community-based sample of Caucasian pedigrees: The Framingham Offspring Study. Diabetes. 2002, 51 (3): 833-840. 10.2337/diabetes.51.3.833.CrossRefPubMed
23.
Panhuysen CI, Cupples LA, Wilson PW, Herbert AG, Myers RH, Meigs JB: A genome scan for loci linked to quantitative insulin traits in persons without diabetes: the Framingham Offspring Study. Diabetologia. 2003, 46 (4): 579-587.PubMed
24.
Atwood LD, Heard-Costa NL, Fox CS, Jaquish CE, Cupples LA: Sex and age specific effects of chromosomal regions linked to body mass index in the Framingham Study. BMC Genet. 2006, 7: 7-10.1186/1471-2156-7-7.PubMedCentralCrossRefPubMed
25.
Atwood LD, Heard-Costa NL, Cupples LA, Jaquish CE, Wilson PW, D'Agostino RB: Genomewide linkage analysis of body mass index across 28 years of the Framingham Heart Study. Am J Hum Genet. 2002, 71 (5): 1044-1050. 10.1086/343822.PubMedCentralCrossRefPubMed
26.
Gottlieb DJ, O'Connor GT, Wilk JB: Genome-wide association of sleep and circadian phenotypes. BMC Med Genet. 2007, 8 (Suppl 1): S9-10.1186/1471-2350-8-S1-S9.PubMedCentralCrossRefPubMed
27.
Newton-Cheh C, Guo C-Y, Wang TJ, O'Donnell CJ, Levy D, Larson MG: Genome-wide association study of electrocardiographic and heart rate variability traits: the Framingham Heart Study. BMC Med Genet. 2007, 8 (Suppl 1): S7-10.1186/1471-2350-8-S1-S7.PubMedCentralCrossRefPubMed
28.
Levy D, Larson MG, Benjamin EJ, Newton-Cheh C, Wang TJ, Hwang SJ, Vasan RS, Mitchell GF: Framingham Heart Study 100K Project: Genome-wide associations for blood pressure and arterial stiffness. BMC Med Genet. 2007, 8 (Suppl 1): S3-10.1186/1471-2350-8-S1-S3.PubMedCentralCrossRefPubMed
29.
O'Donnell CJ, Cupples LA, D'Agostino RB, Fox CS, Hoffmann U, Hwang S-J, Ingellson E, Liu C-Y, Murabito JM, Polak JF, Wolf PA, Demissie S: Genome-wide association study for subclinical atherosclerosis in major arterial territories in the NHLBI's Framingham Heart Study. BMC Med Genet. 2007, 8 (Suppl 1): S4-10.1186/1471-2350-8-S1-S4.PubMedCentralCrossRefPubMed
30.
Larson MG, Atwood LD, Benjamin EJ, Cupples LA, D'Agostino RB, Fox CS, Govindaraju DR, Guo CY, Heard-Costa NL, Hwang SJ, Murabito JM, Newton-Cheh C, O'Donnell CJ, Seshadri S, Vasan RS, Wang TJ, Wolf PA, Levy D: Framingham Heart Study 100K project: genome-wide associations for cardiovascular disease outcomes. BMC Med Genet. 2007, 8 (Suppl 1): S5-10.1186/1471-2350-8-S1-S5.PubMedCentralCrossRefPubMed
31.
Murabito JM, Rosenberg CL, Finger D, Kreger BE, Levy D, Splansky GL, Antman K, Hwang S-J: A genome-wide association study of breast and prostate cancer in the NHLBI's Framingham Heart Study. BMC Med Genet. 2007, 8 (Suppl 1): S6-10.1186/1471-2350-8-S1-S6.PubMedCentralCrossRefPubMed
32.
Wilk JB, Walter RE, Laramie JM, Gottlieb DJ, O'Connor GT: Framingham Heart Study genome-wide association: results for pulmonary function measures. BMC Med Genet. 2007, 8 (Suppl 1): S8-10.1186/1471-2350-8-S1-S8.PubMedCentralCrossRefPubMed
33.
Benjamin EJ, Dupuis J, Larson MG, Lunetta KL, Booth SL, Govindaraju DR, Kathiresan S, Keaney JF, Keyes MJ, Lin JP, Meigs JB, Robins SJ, Rong J, Schnabel R, Vita JA, Wang TJ, Wilson PWF, Wolf PA, Vasan RS: Genome-wide association with select biomarker traits in the Framingham Heart Study. BMC Med Genet. 2007, 8 (Suppl 1): S11-10.1186/1471-2350-8-S1-S11.PubMedCentralCrossRefPubMed
34.
Yang Q, Kathiresan S, Lin JP, Tofler GH, O'Donnell CJ: Genome-wide association and linkage analyses of hemostatic factors and hematological phenotypes in the Framingham Heart Study. BMC Med Genet. 2007, 8 (Suppl 1): S12-10.1186/1471-2350-8-S1-S12.PubMedCentralCrossRefPubMed
35.
Lunetta KL, D'Agostino RB, Karasik D, Benjamin EJ, Guo C-Y, Govindaraju R, Kiel DP, Kelly-Hayes M, Massaro JM, Pencina MJ, Seshadri S, Murabito JM: Genetic correlates of longevity and selected age-related phenotypes: a genome-wide association study in the Framingham Study. BMC Med Genet. 2007, 8 (Suppl 1): S13-10.1186/1471-2350-8-S1-S13.PubMedCentralCrossRefPubMed
36.
Kiel DP, Demissie S, Dupuis J, Lunetta KL, Murabito JM, Karasik D: Genome-wide association with bone mass and geometry in the Framingham Heart Study. BMC Med Genet. 2007, 8 (Suppl 1): S14-10.1186/1471-2350-8-S1-S14.PubMedCentralCrossRefPubMed
37.
Seshadri S, DeStefano AL, Au R, Massaro JM, Beiser AS, Kelly-Hayes M, Kase CS, D'Agostino RB, DeCarli C, Atwood LD, Wolf PA: Genetic correlates of brain aging on MRI and cognitive test measures: a genome-wide association and linkage analysis in the Framingham Study. BMC Med Genet. 2007, 8 (Suppl 1): S15-10.1186/1471-2350-8-S1-S15.PubMedCentralCrossRefPubMed
38.
Meigs JB, Manning AK, Fox CS, Florez JC, Liu C-Y, Cupples LA, Dupuis J: Genome-wide association with diabetes-related traits in the Framingham Heart Study. BMC Med Genet. 2007, 8 (Suppl 1): S16-10.1186/1471-2350-8-S1-S16.PubMedCentralCrossRefPubMed
39.
Kathiresan S, Manning AK, Demissie S, D'Agostino RB, Surti A, Guiducci C, Gianniny L, Burtt NP, Melander O, Orho-Melander M, Arnett D, Peloso GM, Ordovas JM, Cupples LA: A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study. BMC Med Genet. 2007, 8 (Suppl 1): S17-10.1186/1471-2350-8-S1-S17.PubMedCentralCrossRefPubMed
40.
Fox CS, Heard-Costa N, Cupples LA, Dupuis J, Vasan RS, Atwood LD: Genome-wide association to body mass index and waist circumference: the Framingham Heart Study 100K project. BMC Med Genet. 2007, 8 (Suppl 1): S18-10.1186/1471-2350-8-S1-S18.PubMedCentralCrossRefPubMed
41.
Vasan RS, Larson MG, Aragam J, Wang TJ, Mitchell GF, Kathiresan S, Newton-Cheh C, Vita JA, Keyes MJ, O'Donnell CJ, Levy D, Benjamin EJ: Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham Heart Study. BMC Med Genet. 2007, 8 (Suppl 1): S2-10.1186/1471-2350-8-S1-S2.PubMedCentralCrossRefPubMed
42.
Hwang S-J, Yang Q, Meigs JB, Pearce EN, Fox CS: A Genome-Wide Association for Kidney Function and Endocrine-Related Traits in the NHLBI's Framingham Heart Study. BMC Med Genet. 2007, 8 (Suppl 1): S10-10.1186/1471-2350-8-S1-S10.PubMedCentralCrossRefPubMed
43.
Dawber T: The Framingham Study: The Epidemiology of Atherosclerotic Disease. 1980, Cambridge, Massachusetts: Harvard University PressCrossRef
44.
Dawber TRMG, Moore FE: Epidemiologic approaches to heart disease: the Framingham study. Am J Public Health. 1951, 41: 279-286.CrossRef
45.
Dawber TRKW, Lyell LP: An approach to longitudinal studies in a community: the Framingham Heart Study. Ann N Y Acad Sci. 1963, 107: 539-556. 10.1111/j.1749-6632.1963.tb13299.x.CrossRefPubMed
46.
Cupples LA, D'Agostino RB: Some risk factors related to the annual incidence of cardiovascular disease and death using pooled repeated biennial measurements: Framingham Study, 30-year follow-up. The Framingham Heart Study: An Epidemiological Investigation of Cardiovascular Disease. Edited by: Kannel WB, Wolf PA, Garrison RJ. 1987, Washington, DC: Government Printing Office, NIH publication 87-203:
47.
Feinleib M, Kannel WB, Garrison RJ, McNamara PM, Castelli WP: The Framingham Offspring Study: design and preliminary data. Prev Med. 1975, 4: 518-525. 10.1016/0091-7435(75)90037-7.CrossRefPubMed
48.
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
49.
Cupples LA, Yang Q, Demissie S, Copenhafer D, Levy D: Description of the Framingham Heart Study data for Genetic Analysis Workshop 13. BMC Genet. 2003, 4 (Suppl 1): S2-10.1186/1471-2156-4-S1-S2.PubMedCentralCrossRefPubMed
50.
Yang Q, Chazaro I, Cui J, Guo CY, Demissie S, Larson M, Atwood LD, Cupples LA, DeStefano AL: Genetic analyses of longitudinal phenotype data: a comparison of univariate methods and a multivariate approach. BMC Genet. 2003, 4 (Suppl 1): S29-10.1186/1471-2156-4-S1-S29.PubMedCentralCrossRefPubMed
51.
Fox CS, Yang Q, Cupples LA, Guo CY, Larson MG, Leip EP, Wilson PW, Levy D: Genomewide linkage analysis to serum creatinine, GFR, and creatinine clearance in a community-based population: the Framingham Heart Study. J Am Soc Nephrol. 2004, 15 (9): 2457-2461. 10.1097/01.ASN.0000135972.13396.6F.CrossRefPubMed
52.
Fox CS, Cupples LA, Chazaro I, Polak JF, Wolf PA, D'Agostino RB, Ordovas JM, O'Donnell CJ: Genomewide linkage analysis for internal carotid artery intimal medial thickness: evidence for linkage to chromosome 12. Am J Hum Genet. 2004, 74 (2): 253-261. 10.1086/381559.PubMedCentralCrossRefPubMed
53.
Karasik D, Hannan MT, Cupples LA, Felson DT, Kiel DP: Genetic contribution to biological aging: the Framingham Study. J Gerontol A Biol Sci Med Sci. 2004, 59 (3): 218-226.PubMedCentralCrossRefPubMed
54.
Karasik D, Myers RH, Cupples LA, Hannan MT, Gagnon DR, Herbert A, Kiel DP: Genome screen for quantitative trait loci contributing to normal variation in bone mineral density: the Framingham Study. J Bone Miner Res. 2002, 17 (9): 1718-1727. 10.1359/jbmr.2002.17.9.1718.CrossRefPubMed
55.
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 (2): 307-314. 10.1016/j.atherosclerosis.2005.02.015.CrossRefPubMed
56.
Murabito JM, Yang Q, Fox CS, Cupples LA: Genome-wide linkage analysis to age at natural menopause in a community-based sample: the Framingham Heart Study. Fertil Steril. 2005, 84 (6): 1674-1679. 10.1016/j.fertnstert.2005.05.046.CrossRefPubMed
57.
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 (5771): 279-283. 10.1126/science.1124779.CrossRefPubMed
58.
Di X, Matsuzaki H, Webster TA, Hubbell E, Liu G, Dong S, Bartell D, Huang J, Chiles R, Yang G, Shen MM, Kulp D, Kennedy GC, Mei R, Jones KW, Cawley S: Dynamic model based algorithms for screening and genotyping over 100K SNPs on oligonucleotide microarrays. Bioinformatics. 2005, 21 (9): 1958-1963. 10.1093/bioinformatics/bti275.CrossRefPubMed
59.
Weber JL, May PE: Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am J Hum Genet. 1989, 44: 388-396.PubMedCentralPubMed
60.
Yuan BVD, Weber JL, Beck J, Sheffield VC: Improved set of short-tandem-repeat polymorphisms for screening the human genome [letter]. Am J Hum Genet. 1997, 60: 459-460.PubMedCentralPubMed
61.
62.
O'Connell JR, Weeks DE: PedCheck: a program for identification of genotype incompatibilities in linkage analysis. Am J Hum Genet. 1998, 63: 259-266. 10.1086/301904.PubMedCentralCrossRefPubMed
63.
Emigh T: On the number of observed classes from a multinomial distribution. Biometrics. 1983, 39: 485-491. 10.2307/2531019.CrossRef
64.
Warnes G, Leisch F: Genetics: Population Genetics. R package Version 1.1.4. 2005
65.
R_Development_Core_Team: R: A language and environment for statistical computing. 2005, Vienna, Austria: R Foundation for Statistical Computing
66.
Huang Q, Shete S, Amos CI: Ignoring linkage disequilibrium among tightly linked markers induces false-positive evidence of linkage for affected sib pair analysis. Am J Hum Genet. 2004, 75 (6): 1106-1112. 10.1086/426000.PubMedCentralCrossRefPubMed
67.
Huang Q, Shete S, Swartz M, Amos CI: Examining the effect of linkage disequilibrium on multipoint linkage analysis. BMC Genet. 2005, 6 (Suppl 1): S83-10.1186/1471-2156-6-S1-S83.PubMedCentralCrossRefPubMed
68.
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
69.
70.
Rabinowitz D, Laird N: A unified approach to adjusting association tests for population admixture with arbitrary pedigree structure and arbitrary missing marker information. Hum Hered. 2000, 50 (4): 211-223. 10.1159/000022918.CrossRefPubMed
71.
Laird NM, Horvath S, Xu X: Implementing a unified approach to family-based tests of association. Genet Epidemiol. 2000, 19 (Suppl 1): S36-42. 10.1002/1098-2272(2000)19:1+<::AID-GEPI6>3.0.CO;2-M.CrossRefPubMed
72.
Ewens WJ, Spielman RS: What is the significance of a significant TDT?. Hum Hered. 2005, 60 (4): 206-210. 10.1159/000090544.CrossRefPubMed
73.
Ewens WJ, Spielman RS: The transmission/disequilibrium test: history, subdivision, and admixture. Am J Hum Genet. 1995, 57 (1): 455-464.PubMedCentralPubMed
74.
Liang KY, Zeger SL: Longitudinal Data Analysis using Generalized Linear Models. Biometrika. 1986, 73: 13-22. 10.1093/biomet/73.1.13.CrossRef
75.
Carey VJ, ported to R by Thomas Lumley (versions 3.13 and 4.4) and Brian Ripley (version 4.13): gee: Generalized Estimation Equation solver. R package Version 4.13-10. 2002
76.
Wilk JB, Manning AK, Dupuis J, Cupples LA, Larson MG, Newton-Cheh C, Demissie S, DeStefano AL, Hwang SJ, Liu C, Yang Q, Lunetta KL: No evidence of major population substructure in the Framingham Heart Study. Abstract 171 from the 14th Annual Meeting of the International Genetic Epidemiology Society. Genet Epidemiol. 2005, 29: 286-
77.
Clayton DG, Walker NM, Smyth DJ, Pask R, Cooper JD, Maier LM, Smink LJ, Lam AC, Ovington NR, Stevens HE, Nutland S, Howson JM, Faham M, Moorhead M, Jones HB, Falkowski M, Hardenbol P, Willis TD, Todd JA: Population structure, differential bias and genomic control in a large-scale, case-control association study. Nat Genet. 2005, 37 (11): 1243-1246. 10.1038/ng1653.CrossRefPubMed
78.
Kathiresan S, Yang Q, Larson MG, Camargo AL, Tofler GH, Hirschhorn JN, Gabriel SB, O'Donnell CJ: Common genetic variation in five thrombosis genes and relations to plasma hemostatic protein level and cardiovascular disease risk. Arterioscler Thromb Vasc Biol. 2006, 26 (6): 1405-1412. 10.1161/01.ATV.0000222011.13026.25.CrossRefPubMed
79.
Rogaeva E, Meng Y, Lee JH, Gu Y, Kawarai T, Zou F, Katayama T, Baldwin CT, Cheng R, Hasegawa H, Chen F, Shibata N, Lunetta KL, Pardossi-Piquard R, Bohm C, Wakutani Y, Cupples LA, Cuenco KT, Green RC, Pinessi L, Rainero I, Sorbi S, Bruni A, Duara R, Friedland R, Inzelberg R, Hampe W, Bujo H, Song Y, Andersen O, Graff-Radford N, Petersen R, Dickson D, Der SD, Fraser PE, Schmitt-Ulms G, Younkin S, Mayeux R, Farrer LA, St George-Hyslop P: The sortilin-related receptor SORL1 is genetically associated with Alzheimer's Disease. Nat Genet. 2007, 39 (2): 168-177. 10.1038/ng1943.PubMedCentralCrossRefPubMed
80.
Diabetes Genetics Initiative of Broad Institute of Harvard and MIT LU, and Novartis Institutes of BioMedical Research, Saxena R, Voight BF, Lyssenko V, Burtt NP, de Bakker PI, Chen H, Roix JJ, Kathiresan S, Hirschhorn JN, Daly MJ, Hughes TE, Groop L, Altshuler D, Almgren P, Florez JC, Meyer J, Ardlie K, Bengtsson Bostrom K, Isomaa B, Lettre G, Lindblad U, Lyon HN, Melander O, Newton-Cheh C, Nilsson P, Orho-Melander M, Rastam L, Speliotes EK, Taskinen MR, Tuomi T, Guiducci C, Berglund A, Carlson J, Gianniny L, Hackett R, Hall L, Holmkvist J, Laurila E, Sjogren M, Sterner M, Surti A, Svensson M, Svensson M, Tewhey R, Blumenstiel B, Parkin M, Defelice M, Barry R, Brodeur W, Camarata J, Chia N, Fava M, Gibbons J, Handsaker B, Healy C, Nguyen K, Gates C, Sougnez C, Gage D, Nizzari M, Gabriel SB, Chirn GW, Ma Q, Parikh H, Richardson D, Ricke D, Purcell S: Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science. 2007, 316 (5829): 1331-1336. 10.1126/science.1142358.CrossRef
81.
Sladek R, Rocheleau G, Rung J, Dina C, Shen L, Serre D, Boutin P, Vincent D, Belisle A, Hadjadj S, Balkau B, Heude B, Charpentier G, Hudson TJ, Montpetit A, Pshezhetsky AV, Prentki M, Posner BI, Balding DJ, Meyre D, Polychronakos C, Froguel P: A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature. 2007, 445 (7130): 881-885. 10.1038/nature05616.CrossRefPubMed
82.
Helgadottir A, Thorleifsson G, Manolescu A, Gretarsdottir S, Blondal T, Jonasdottir A, Jonasdottir A, Sigurdsson A, Baker A, Palsson A, Masson G, Gudbjartsson D, Magnusson KP, Andersen K, Levey AI, Backman VM, Matthiasdottir S, Jonsdottir T, Palsson S, Einarsdottir H, Gunnarsdottir S, Gylfason A, Vaccarino V, Hooper WC, Reilly MP, Granger CB, Austin H, Rader DJ, Shah SH, Quyyumi AA, Gulcher JR, Thorgeirsson G, Thorsteinsdottir U, Kong A, Stefansson K: A Common Variant on Chromosome 9p21 Affects the Risk of Myocardial Infarction. Science. 2007, 316 (5830): 1491-1493. 10.1126/science.1142842.CrossRefPubMed
83.
McPherson R, Pertsemlidis A, Kavaslar N, Stewart A, Roberts R, Cox DR, Hinds DA, Pennacchio LA, Tybjaerg-Hansen A, Folsom AR, Boerwinkle E, Hobbs HH, Cohen JC: A Common Allele on Chromosome 9 Associated with Coronary Heart Disease. Science. 2007, 316 (5830): 1488-1491. 10.1126/science.1142447.PubMedCentralCrossRefPubMed
84.
Steinthorsdottir V, Thorleifsson G, Reynisdottir I, Benediktsson R, Jonsdottir T, Walters GB, Styrkarsdottir U, Gretarsdottir S, Emilsson V, Ghosh S, Baker A, Snorradottir S, Bjarnason H, Ng MC, Hansen T, Bagger Y, Wilensky RL, Reilly MP, Adeyemo A, Chen Y, Zhou J, Gudnason V, Chen G, Huang H, Lashley K, Doumatey A, So WY, Ma RC, Andersen G, Borch-Johnsen K, Jorgensen T, van Vliet-Ostaptchouk JV, Hofker MH, Wijmenga C, Christiansen C, Rader DJ, Rotimi C, Gurney M, Chan JC, Pedersen O, Sigurdsson G, Gulcher JR, Thorsteinsdottir U, Kong A, Stefansson K: A variant in CDKAL1 influences insulin response and risk of type 2 diabetes. Nat Genet. 2007, 9 (6): 770-775. 10.1038/ng2043.CrossRef
85.
Scott LJ, Mohlke KL, Bonnycastle LL, Willer CJ, Li Y, Duren WL, Erdos MR, Stringham HM, Chines PS, Jackson AU, Prokunina-Olsson L, Ding CJ, Swift AJ, Narisu N, Hu T, Pruim R, Xiao R, Li XY, Conneely KN, Riebow NL, Sprau AG, Tong M, White PP, Hetrick KN, Barnhart MW, Bark CW, Goldstein JL, Watkins L, Xiang F, Saramies J, Buchanan TA, Watanabe RM, Valle TT, Kinnunen L, Abecasis GR, Pugh EW, Doheny KF, Bergman RN, Tuomilehto J, Collins FS, Boehnke M: A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science. 2007, 5829 (5829): 1341-1345. 10.1126/science.1142382.CrossRef
86.
Zeggini E, Weedon MN, Lindgren CM, Frayling TM, Elliott KS, Lango H, Timpson NJ, Perry JR, Rayner NW, Freathy RM, Barrett JC, Shields B, Morris AP, Ellard S, Groves CJ, Harries LW, Marchini JL, Owen KR, Knight B, Cardon LR, Walker M, Hitman GA, Morris AD, AS D, Wellcome Trust Case Control Consortium (WTCCC), Burton PR, Clayton DG, Craddock N, Deloukas P, Duncanson A, Kwiatkowski DP, Ouwehand WH, Samani NJ, Todd JA, Donnelly P, Davison D, Easton D, Evans D, Leung HT, Spencer CC, Tobin MD, Attwood AP, Boorman JP, Cant B, Everson U, Hussey JM, Jolley JD, Knight AS, Koch K, Meech E, Nutland S, Prowse CV, Stevens HE, Taylor NC, Walters GR, Walker NM, Watkins NA, Winzer T, Jones RW, McArdle WL, Ring SM, Strachan DP, Pembrey M, Breen G, St Clair D, Caesar S, Gordon-Smith K, Jones L, Fraser C, Green EK, Grozeva D, Hamshere ML, Holmans PA, Jones IR, Kirov G, Moskvina V, Nikolov I, O'donovan MC, Owen MJ, Collier DA, Elkin A, Farmer A, Williamson R, McGuffin P, Young AH, Ferrier IN, Ball SG, Balmforth AJ, Barrett JH, Bishop DT, Iles MM, Maqbool A, Yuldasheva N, Hall AS, Braund PS, Dixon RJ, Mangino M, Stevens S, Thompson JR, Bredin F, Tremelling M, Parkes M, Drummond H, Lees CW, Nimmo ER, Satsangi J, Fisher SA, Forbes A, Lewis CM, Onnie CM, Prescott NJ, Sanderson J, Mathew CG, Barbour J, Mohiuddin MK, Todhunter CE, Mansfield JC, Ahmad T, Cummings FR, Jewell DP, Webster J, Brown MJ, Lathrop GM, Connell J, Dominiczak A, Braga Marcano CA, Burke B, Dobson R, Gungadoo J, Lee KL, Munroe PB, Newhouse SJ, Onipinla A, Wallace C, Xue M, Caulfield M, Farrall M, Barton A, Bruce IN, Donovan H, Eyre S, Gilbert PD, Hider SL, Hinks AM, John SL, Potter C, Silman AJ, Symmons DP, Thomson W, Worthington J, Dunger DB, Widmer B, Newport M, Sirugo G, Lyons E, Vannberg F, Hill AV, Bradbury LA, Farrar C, Pointon JJ, Wordsworth P, Brown MA, Franklyn JA, Heward JM, Simmonds MJ, Gough SC, Seal S, Stratton MR, Rahman N, Ban M, Goris A, Sawcer SJ, Compston A, Conway D, Jallow M, Rockett KA, Bumpstead SJ, Chaney A, Downes K, Ghori MJ, Gwilliam R, Hunt SE, Inouye M, Keniry A, King E, McGinnis R, Potter S, Ravindrarajah R, Whittaker P, Widden C, Withers D, Cardin NJ, Ferreira T, Pereira-Gale J, Hallgrimsdottir IB, Howie BN, Su Z, Teo YY, Vukcevic D, Bentley D, Compston A, Ouwehand NJ, Samani MR, Isaacs JD, Morgan AW, Wilson GD, Ardern-Jones A, Berg J, Brady A, Bradshaw N, Brewer C, Brice G, Bullman B, Campbell J, Castle B, Cetnarsryj R, Chapman C, Chu C, Coates N, Cole T, Davidson R, Donaldson A, Dorkins H, Douglas F, Eccles D, Eeles R, Elmslie F, Evans DG, Goff S, Goodman S, Goudie D, Gray J, Greenhalgh L, Gregory H, Hodgson SV, Homfray T, Houlston RS, Izatt L, Jackson L, Jeffers L, Johnson-Roffey V, Kavalier F, Kirk C, Lalloo F, Langman C, Locke I, Longmuir M, Mackay J, Magee A, Mansour S, Miedzybrodzka Z, Miller J, Morrison P, Murday V, Paterson J, Pichert G, Porteous M, Rahman N, Rogers M, Rowe S, Shanley S, Saggar A, Scott G, Side L, Snadden L, Steel M, Thomas M, Thomas S, McCarthy MI, Hattersley AT: Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science. 2007, 316 (5829): 1336-1341. 10.1126/science.1142364.PubMedCentralCrossRefPubMed
87.
Herbert A, Lenburg ME, Ulrich D, Gerry NP, Schlauch K, Christman MF: Open-access database of candidate associations from a genome-wide SNP scan of the Framingham Heart Study. Nat Genet. 2007, 39 (2): 135-136. 10.1038/ng0207-135.CrossRefPubMed
88.
The International HapMap Consortium: A haplotype map of the human genome. Nature. 2005, 437 (7063): 1299-1320. 10.1038/nature04226.PubMedCentralCrossRef
89.
Rabbee N, Speed TP: A genotype calling algorithm for Affymetrix SNP arrays. Bioinformatics. 2006, 22: 7-12. 10.1093/bioinformatics/bti741.CrossRefPubMed
90.
Nicolae DL, Wen X, Voight BF, Cox NJ: Coverage and Characteristics of the Affymetrix GeneChip Human Mapping 100K SNP Set. PLoS Genetics. 2006, 2 (5): e67-10.1371/journal.pgen.0020067.PubMedCentralCrossRefPubMed
Metadata
Title
The Framingham Heart Study 100K SNP genome-wide association study resource: overview of 17 phenotype working group reports
Authors
L Adrienne Cupples
Heather T Arruda
Emelia J Benjamin
Ralph B D'Agostino Sr
Serkalem Demissie
Anita L DeStefano
Josée Dupuis
Kathleen M Falls
Caroline S Fox
Daniel J Gottlieb
Diddahally R Govindaraju
Chao-Yu Guo
Nancy L Heard-Costa
Shih-Jen Hwang
Sekar Kathiresan
Douglas P Kiel
Jason M Laramie
Martin G Larson
Daniel Levy
Chun-Yu Liu
Kathryn L Lunetta
Matthew D Mailman
Alisa K Manning
James B Meigs
Joanne M Murabito
Christopher Newton-Cheh
George T O'Connor
Christopher J O'Donnell
Mona Pandey
Sudha Seshadri
Ramachandran S Vasan
Zhen Y Wang
Jemma B Wilk
Philip A Wolf
Qiong Yang
Larry D Atwood
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-S1

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