Birth cohort, age, and sex strongly modulate effects of lipid risk alleles identified in genome-wide association studies

PLoS ONE

Volumn 10, Issue 8, 2015, Pages

  Kulminski, Alexander M ^a   Culminskaya, Irina ^a   Arbeev, Konstantin G ^a   Arbeeva, Liubov ^a   Ukraintseva, Svetlana V ^a   Stallard, Eric ^a   Wu, Deqing ^a   Yashin, Anatoliy I ^a  

^a DUKE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHOLESTEROL; HEPATOCYTE NUCLEAR FACTOR 4ALPHA; HFE PROTEIN; HLA DR ANTIGEN; URATE TRANSPORTER;

ADULT; AGE; ARTICLE; BIRTH; CETP GENE; CHOLESTEROL BLOOD LEVEL; COHORT ANALYSIS; CONTROLLED STUDY; EFCAB13 GENE; ENVIRONMENTAL EXPOSURE; FEMALE; FRK GENE; GENE; GENE FUNCTION; GENETIC ASSOCIATION; GENOTYPE; HEREDITY; HFE GENE; HLA DRA GENE; HNF4A GENE; HUMAN; MALE; PCSK9 GENE; SEX; SINGLE NUCLEOTIDE POLYMORPHISM; SLC22A1 GENE; SPTY2D1 GENE; ST3GAL4 GENE; ALLELE; BLOOD; EPIDEMIOLOGY; GENETIC PREDISPOSITION; GENETICS; GENOME-WIDE ASSOCIATION STUDY; META ANALYSIS; QUANTITATIVE TRAIT; SEX DIFFERENCE; STATISTICS AND NUMERICAL DATA;

ADULT; AGE FACTORS; ALLELES; CHOLESTEROL; FEMALE; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HUMANS; MALE; POLYMORPHISM, SINGLE NUCLEOTIDE; QUANTITATIVE TRAIT, HERITABLE; SEX FACTORS;

EID: 84942882007     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0136319     Document Type: Article

References (82)

1. Sierra F, Hadley E, Suzman R, Hodes R. Prospects for life span extension. Annu Rev Med. 2009; 60: 457-69. Epub 2008/09/27. doi: 10.1146/annurev.med.60.061607.220533 PMID: 18817460.
2. Olshansky SJ, Perry D, Miller RA, Butler RN. Pursuing the longevity dividend: Scientific goals for an aging world. Ann N Y Acad Sci. 2007; 1114: 11-3. Epub 2007/11/08. doi: 1114/1/11 [pii] doi: 10.1196/annals.1396.050 PMID: 17986572.
3. Aging NIo. Living Long & Well in the 21st Century: Strategic Directions for Research on Aging 2010 [cited 2013 May, 15]. Available from: Http://www.nia.nih.gov/sites/default/files/strategic-plan108.pdf.
4. Gibson G. Rare and common variants: Twenty arguments. Nat Rev Genet. 2011; 13 (2) : 135-45. Epub 2012/01/19. doi: Nrg3118 [pii] doi: 10.1038/nrg3118 PMID: 22251874.
5. Eichler EE, Flint J, Gibson G, Kong A, Leal SM, Moore JH, et al. Missing heritability and strategies for finding the underlying causes of complex disease. Nat Rev Genet. 2010; 11 (6) : 446-50. Epub 2010/05/19. doi: Nrg2809 [pii] doi: 10.1038/nrg2809 PMID: 20479774; PubMed Central PMCID: PMC2942068.
6. MacRae CA, Vasan RS. Next-generation genome-wide association studies: Time to focus on phenotype? Circ Cardiovasc Genet. 2011; 4 (4) : 334-6. Epub 2011/08/19. doi: 4/4/334 [pii] doi: 10.1161/CIRCGENETICS.111.960765 PMID: 21846867; PubMed Central PMCID: PMC3187849.
7. Kulminski AM. Unraveling genetic origin of aging-related traits: Evolving concepts. Rejuvenation Res. 2013; 16 (4) : 304-12. Epub 2013/06/19. doi: 10.1089/rej.2013.1441 PMID: 23768105; PubMed Central PMCID: PMC3746287.
8. Vijg J, Suh Y. Genetics of longevity and aging. Annu Rev Med. 2005; 56: 193-212. Epub 2005/01/22. doi: 10.1146/annurev.med.56.082103.104617 PMID: 15660509.
9. Vaupel JW. Biodemography of human ageing. Nature. 2010; 464 (7288) : 536-42. Epub 2010/03/26. doi: Nature08984 [pii] doi: 10.1038/nature08984 PMID: 20336136.
10. Teslovich TM, Musunuru K, Smith AV, Edmondson AC, Stylianou IM, Koseki M, et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature. 2010; 466 (7307) : 707-13. Epub 2010/08/06. doi: Nature09270 [pii] doi: 10.1038/nature09270 PMID: 20686565; PubMed Central PMCID: PMC3039276.
11. Watt AJ, Garrison WD, Duncan SA. HNF4: A central regulator of hepatocyte differentiation and function. Hepatology. 2003; 37 (6) : 1249-53. Epub 2003/05/30. doi: 10.1053/jhep.2003.50273 S0270913903004208 [pii]. PMID: 12774000.
12. Bolotin E, Liao H, Ta TC, Yang C, Hwang-Verslues W, Evans JR, et al. Integrated approach for the identification of human hepatocyte nuclear factor 4alpha target genes using protein binding microarrays. Hepatology. 2010; 51 (2) : 642-53. Epub 2010/01/08. doi: 10.1002/hep.23357 PMID: 20054869; PubMed Central PMCID: PMC3581146.
13. Seidah NG, Benjannet S, Wickham L, Marcinkiewicz J, Jasmin SB, Stifani S, et al. The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1) : Liver regeneration and neuronal differentiation. Proc Natl Acad Sci U S A. 2003; 100 (3) : 928-33. Epub 2003/01/29. doi: 10.1073/pnas. 0335507100 0335507100 [pii]. PMID: 12552133; PubMed Central PMCID: PMC298703.
14. Bonde Y, Breuer O, Luetjohann D, Sjoberg S, Angelin B, Rudling M. Thyroid hormone reduces PCSK9 and stimulates bile acid synthesis in humans. J Lipid Res. 2014. Epub 2014/08/31. doi: Jlr.M051664 [pii] doi: 10.1194/jlr.M051664 PMID: 25172631.
15. Baass A, Dubuc G, Tremblay M, Delvin EE, O'Loughlin J, Levy E, et al. Plasma PCSK9 is associated with age, sex, and multiple metabolic markers in a population-based sample of children and adolescents. Clin Chem. 2009; 55 (9) : 1637-45. Epub 2009/07/25. doi: Clinchem.2009.126987 [pii] doi: 10. 1373/clinchem.2009.126987 PMID: 19628659.
16. Lakoski SG, Lagace TA, Cohen JC, Horton JD, Hobbs HH. Genetic and metabolic determinants of plasma PCSK9 levels. J Clin Endocrinol Metab. 2009; 94 (7) : 2537-43. Epub 2009/04/09. doi: Jc.2009- 0141 [pii] doi: 10.1210/jc.2009-0141 PMID: 19351729; PubMed Central PMCID: PMC2708952.
17. Rezen T, Rozman D, Pascussi JM, Monostory K. Interplay between cholesterol and drug metabolism. Biochim Biophys Acta. 2011; 1814 (1) : 146-60. Epub 2010/06/24. doi: S1570-9639 (10) 00139-1 [pii] doi: 10.1016/j.bbapap.2010.05.014 PMID: 20570756.
18. Ganz T. Molecular control of iron transport. J Am Soc Nephrol. 2007; 18 (2) : 394-400. Epub 2007/01/19. doi: ASN.2006070802 [pii] doi: 10.1681/ASN.2006070802 PMID: 17229910.
19. Takami T, Sakaida I. Iron regulation by hepatocytes and free radicals. J Clin Biochem Nutr. 2011; 48 (2) : 103-6. Epub 2011/03/05. doi: 10.3164/jcbn.10-76 PMID: 21373260; PubMed Central PMCID: PMC3045680.
20. Rohrlich PS, Fazilleau N, Ginhoux F, Firat H, Michel F, Cochet M, et al. Direct recognition by alphabeta cytolytic T cells of Hfe, a MHC class Ib molecule without antigen-presenting function. Proc Natl Acad Sci U S A. 2005; 102 (36) : 12855-60. Epub 2005/08/27. doi: 0502309102 [pii] doi: 10.1073/pnas. 0502309102 PMID: 16123136; PubMed Central PMCID: PMC1200262.
21. Truksa J, Lee P, Beutler E. Two BMP responsive elements, STAT, and bZIP/HNF4/COUP motifs of the hepcidin promoter are critical for BMP, SMAD1, and HJV responsiveness. Blood. 2009; 113 (3) : 688-95. Epub 2008/11/11. doi: Blood-2008-05-160184 [pii] doi: 10.1182/blood-2008-05-160184 PMID: 18997172; PubMed Central PMCID: PMC2628375.
22. Jiang K, Frank MB, Chen Y, Osban J, Jarvis JN. Genomic characterization of remission in juvenile idiopathic arthritis. Arthritis Res Ther. 2013; 15 (4) : R100. Epub 2013/09/05. doi: Ar4280 [pii] doi: 10.1186/ar4280 PMID: 24000795.
23. Broxmeyer HE, Cooper S, Hangoc G, Chang CH. Class II transactivator-mediated regulation of major histocompatibility complex class II antigen expression is important for hematopoietic progenitor cell suppression by chemokines and iron-binding proteins. Exp Hematol. 2006; 34 (8) : 1078-84. Epub 2006/07/26. doi: S0301-472X (06) 00246-3 [pii] doi: 10.1016/j.exphem.2006.04.008 PMID: 16863914.
24. Chelladurai M, Honn KV, Walz DA. HLA-DR is a procoagulant. Biochem Biophys Res Commun. 1991; 178 (2) : 467-73. Epub 1991/07/31. doi: 0006-291X (91) 90130-Y [pii]. PMID: 1859406.
25. Chandrasekharan S, Qiu TH, Alkharouf N, Brantley K, Mitchell JB, Liu ET. Characterization of mice deficient in the Src family nonreceptor tyrosine kinase Frk/rak. Mol Cell Biol. 2002; 22 (14) : 5235-47. Epub 2002/06/22. PMID: 12077350; PubMed Central PMCID: PMC139782.
26. Pibiri M, Ledda-Columbano GM, Cossu C, Simbula G, Menegazzi M, Shinozuka H, et al. Cyclin D1 is an early target in hepatocyte proliferation induced by thyroid hormone (T3) . FASEB J. 2001; 15 (6) : 1006-13. Epub 2001/04/09. PMID: 11292661.
27. Timchenko NA. Aging and liver regeneration. Trends Endocrinol Metab. 2009; 20 (4) : 171-6. Epub 2009/04/11. doi: S1043-2760 (09) 00039-3 [pii] doi: 10.1016/j.tem.2009.01.005 PMID: 19359195.
28. Zhang Q, Lei X, Lu H. Alterations of epigenetic signatures in hepatocyte nuclear factor 4alpha deficient mouse liver determined by improved ChIP-qPCR and (h) MeDIP-qPCR assays. PLoS One. 2014; 9 (1) : E84925. Epub 2014/01/16. doi: 10.1371/journal.pone.0084925 PONE-D-13-30177 [pii]. PMID: 24427299; PubMed Central PMCID: PMC3888413.
29. Osakabe A, Tachiwana H, Takaku M, Hori T, Obuse C, Kimura H, et al. Vertebrate Spt2 is a novel nucleolar histone chaperone that assists in ribosomal DNA transcription. J Cell Sci. 2013; 126 (Pt 6) : 1323-32. Epub 2013/02/05. doi: Jcs.112623 [pii] doi: 10.1242/jcs.112623 PMID: 23378026.
30. Daigo K, Kawamura T, Ohta Y, Ohashi R, Katayose S, Tanaka T, et al. Proteomic analysis of native hepatocyte nuclear factor-4alpha (HNF4alpha) isoforms, phosphorylation status, and interactive cofactors. J Biol Chem. 2011; 286 (1) : 674-86. Epub 2010/11/05. doi: M110.154732 [pii] doi: 10.1074/jbc. M110.154732 PMID: 21047794; PubMed Central PMCID: PMC3013027.
31. Zacharski LR, Ornstein DL, Woloshin S, Schwartz LM. Association of age, sex, and race with body iron stores in adults: Analysis of NHANES III data. Am Heart J. 2000; 140 (1) : 98-104. Epub 2000/06/30. doi: S0002-8703 (00) 41567-X [pii] doi: 10.1067/mhj.2000.106646 PMID: 10874269.
32. Kumar R, Burns EA. Age-related decline in immunity: Implications for vaccine responsiveness. Expert Rev Vaccines. 2008; 7 (4) : 467-79. Epub 2008/05/01. doi: 10.1586/14760584.7.4.467 PMID: 18444893.
33. Peeters RP. Thyroid hormones and aging. Hormones (Athens) . 2008; 7 (1) : 28-35. Epub 2008/03/25. PMID: 18359742.
34. Lebel M, de Souza-Pinto NC, Bohr VA. Metabolism, genomics, and DNA repair in the mouse aging liver. Curr Gerontol Geriatr Res. 2011; 2011: 859415. Epub 2011/05/12. doi: 10.1155/2011/859415 PMID: 21559242; PubMed Central PMCID: PMC3087416.
35. Ellies LG, Ditto D, Levy GG, Wahrenbrock M, Ginsburg D, Varki A, et al. Sialyltransferase ST3Gal-IV operates as a dominant modifier of hemostasis by concealing asialoglycoprotein receptor ligands. Proc Natl Acad Sci U S A. 2002; 99 (15) : 10042-7. Epub 2002/07/05. doi: 10.1073/pnas.142005099 142005099 [pii]. PMID: 12097641; PubMed Central PMCID: PMC126621.
36. Sage AP, Mallat Z. Sialyltransferase activity and atherosclerosis. Circ Res. 2014; 114 (6) : 935-7. Epub 2014/03/15. doi: CIRCRESAHA.114.303480 [pii] doi: 10.1161/CIRCRESAHA.114.303480 PMID: 24625722.
37. Deguchi H, Fernandez JA, Griffin JH. Plasma cholesteryl ester transfer protein and blood coagulability. Thromb Haemost. 2007; 98 (6) : 1160-4. Epub 2007/12/08. doi: 07121160 [pii]. PMID: 18064308.
38. Mineo C, Deguchi H, Griffin JH, Shaul PW. Endothelial and antithrombotic actions of HDL. Circ Res. 2006; 98 (11) : 1352-64. Epub 2006/06/10. doi: 98/11/1352 [pii] doi: 10.1161/01.RES.0000225982. 01988.93 PMID: 16763172.
39. Milman S, Atzmon G, Crandall J, Barzilai N. Phenotypes and genotypes of high density lipoprotein cholesterol in exceptional longevity. Curr Vasc Pharmacol. 2014; 12 (5) : 690-7. Epub 2013/12/20. doi: CVP-EPUB-58159 [pii]. PMID: 24350928; PubMed Central PMCID: PMC4087084.
40. Mari D, Mannucci PM, Coppola R, Bottasso B, Bauer KA, Rosenberg RD. Hypercoagulability in centenarians: The paradox of successful aging. Blood. 1995; 85 (11) : 3144-9. Epub 1995/06/01. PMID: 7756646.
41. Atzmon G, Pollin TI, Crandall J, Tanner K, Schechter CB, Scherer PE, et al. Adiponectin levels and genotype: A potential regulator of life span in humans. J Gerontol A Biol Sci Med Sci. 2008; 63 (5) : 447-53. Epub 2008/05/31. doi: 63/5/447 [pii]. PMID: 18511746.
42. Matsumoto C, Ito M, Yamada H, Yamakawa N, Yoshida H, Date A, et al. Genes that characterize T3- predominant Graves' thyroid tissues. Eur J Endocrinol. 2013; 168 (2) : 137-44. Epub 2012/10/31. doi: EJE-12-0507 [pii] doi: 10.1530/EJE-12-0507 PMID: 23109646.
43. Willer CJ, Schmidt EM, Sengupta S, Peloso GM, Gustafsson S, Kanoni S, et al. Discovery and refinement of loci associated with lipid levels. Nat Genet. 2013; 45 (11) : 1274-83. Epub 2013/10/08. doi: Ng.2797 [pii] doi: 10.1038/ng.2797 PMID: 24097068; PubMed Central PMCID: PMC3838666.
44. Corella D, Ordovas JM. Aging and cardiovascular diseases: The role of gene-diet interactions. Ageing Res Rev. 2014; 18: 53-73. Epub 2014/08/28. doi: S1568-1637 (14) 00103-2 [pii] doi: 10.1016/j.arr.2014. 08.002 PMID: 25159268.
45. Lambert G, Charlton F, Rye KA, Piper DE. Molecular basis of PCSK9 function. Atherosclerosis. 2009; 203 (1) : 1-7. Epub 2008/07/25. doi: S0021-9150 (08) 00437-1 [pii] doi: 10.1016/j.atherosclerosis.2008. 06.010 PMID: 18649882.
46. Horton JD, Cohen JC, Hobbs HH. PCSK9: A convertase that coordinates LDL catabolism. J Lipid Res. 2009; 50 Suppl: S172-7. Epub 2008/11/21. doi: R800091-JLR200 [pii] doi: 10.1194/jlr.R800091- JLR200 PMID: 19020338; PubMed Central PMCID: PMC2674748.
47. Ordovas JM. Gender, a significant factor in the cross talk between genes, environment, and health. Gend Med. 2007; 4 Suppl B: S111-22. Epub 2007/12/25. doi: S1550-8579 (07) 80052-0 [pii]. PMID: 18156097.
48. Rieker PP, Bird CE. Rethinking gender differences in health: Why we need to integrate social and biological perspectives. J Gerontol B Psychol Sci Soc Sci. 2005; 60 Spec No 2: 40-7. Epub 2005/10/28. PMID: 16251589.
49. Verbrugge LM, Wingard DL. Sex differentials in health and mortality. Health Matrix. 1987; 5 (2) : 3-19. PMID: 10283417.
50. Migeon BR. The role of X inactivation and cellular mosaicism in women's health and sex-specific diseases. JAMA. 2006; 295 (12) : 1428-33. Epub 2006/03/23. doi: 10.1001/jama.295.12.1428 PMID: 16551715.
51. Kolovou G, Damaskos D, Anagnostopoulou K, Cokkinos DV. Apolipoprotein E gene polymorphism and gender. Ann Clin Lab Sci. 2009; 39 (2) : 120-33. Epub 2009/05/12. doi: 39/2/120 [pii]. PMID: 19429797.
52. Corella D, Peloso G, Arnett DK, Demissie S, Cupples LA, Tucker K, et al. APOA2, dietary fat, and body mass index: Replication of a gene-diet interaction in 3 independent populations. Arch Intern Med. 2009; 169 (20) : 1897-906. Epub 2009/11/11. doi: 169/20/1897 [pii] doi: 10.1001/archinternmed.2009.343 PMID: 19901143; PubMed Central PMCID: PMC2874956.
53. Ordovas JM, Corella D. Nutritional genomics. Annu Rev Genomics Hum Genet. 2004; 5: 71-118. Epub 2004/10/16. doi: 10.1146/annurev.genom.5.061903.180008 PMID: 15485344.
54. Neel JV, Weder AB, Julius S. Type II diabetes, essential hypertension, and obesity as "syndromes of impaired genetic homeostasis": The "thrifty genotype" hypothesis enters the 21st century. Perspect Biol Med. 1998; 42 (1) : 44-74. Epub 1999/01/23. PMID: 9894356.
55. Kuningas M, Mooijaart SP, van Heemst D, Zwaan BJ, Slagboom PE, Westendorp RG. Genes encoding longevity: From model organisms to humans. Aging Cell. 2008; 7 (2) : 270-80. Epub 2008/01/23. doi: ACE366 [pii] doi: 10.1111/j.1474-9726.2008.00366.x PMID: 18208581.
56. Boomsma DI, Kempen HJ, Gevers Leuven JA, Havekes L, de Knijff P, Frants RR. Genetic analysis of sex and generation differences in plasma lipid, lipoprotein, and apolipoprotein levels in adolescent twins and their parents. Genet Epidemiol. 1996; 13 (1) : 49-60. Epub 1996/01/01. doi: 10.1002/(SICI) 1098-2272 (1996) 13: 13.0.CO;2-1 [pii]. PMID: 8647378.
57. Hershcopf RJ, Elahi D, Andres R, Baldwin HL, Raizes GS, Schocken DD, et al. Longitudinal changes in serum cholesterol in man: An epidemiologic search for an etiology. J Chronic Dis. 1982; 35 (2) : 101-14. Epub 1982/02/01. PMID: 7056835.
58. Scheen AJ. Diabetes mellitus in the elderly: Insulin resistance and/or impaired insulin secretion? Diabetes Metab. 2005; 31 Spec No 2: 5S27-5S34. Epub 2006/01/18. doi: MDOI-DM-12-2005-31-HS2-1262- 3636-101019-200509653 [pii]. PMID: 16415763.
59. Yashin AI, Akushevich IV, Arbeev KG, Akushevich L, Ukraintseva SV, Kulminski A. Insights on aging and exceptional longevity from longitudinal data: Novel findings from the Framingham Heart Study. Age. 2006; 28 (4) : 363-74. PMID: ISI: 000243203700006.
60. Akushevich I, Kravchenko J, Ukraintseva S, Arbeev K, Yashin AI. Age patterns of incidence of geriatric disease in the u.s. Elderly population: Medicare-based analysis. J Am Geriatr Soc. 2012; 60 (2) : 323-7. Epub 2012/01/31. doi: 10.1111/j.1532-5415.2011.03786.x PMID: 22283485; PubMed Central PMCID: PMC3288526.
61. De Benedictis G, Carotenuto L, Carrieri G, De Luca M, Falcone E, Rose G, et al. Age-related changes of the 3'APOB-VNTR genotype pool in ageing cohorts. Ann Hum Genet. 1998; 62 (Pt 2) : 115-22. Epub 1998/10/06. doi: 10.1046/j.1469-1809.1998.6220115.x PMID: 9759473.
62. Ilveskoski E, Perola M, Lehtimaki T, Laippala P, Savolainen V, Pajarinen J, et al. Age-dependent association of apolipoprotein E genotype with coronary and aortic atherosclerosis in middle-aged men: An autopsy study. Circulation. 1999; 100 (6) : 608-13. Epub 1999/08/10. PMID: 10441097.
63. Yashin AI, Ukraintseva SV, De Benedictis G, Anisimov VN, Butov AA, Arbeev K, et al. Have the oldest old adults ever been frail in the past? A hypothesis that explains modern trends in survival. J Gerontol A Biol Sci Med Sci. 2001; 56 (10) : B432-42. PMID: 11584028.
64. Jarvik GP, Austin MA, Fabsitz RR, Auwerx J, Reed T, Christian JC, et al. Genetic influences on agerelated change in total cholesterol, low density lipoprotein-cholesterol, and triglyceride levels: Longitudinal apolipoprotein E genotype effects. Genet Epidemiol. 1994; 11 (4) : 375-84. Epub 1994/01/01. doi: 10.1002/gepi.1370110407 PMID: 7813899.
65. Jarvik GP, Goode EL, Austin MA, Auwerx J, Deeb S, Schellenberg GD, et al. Evidence that the apolipoprotein E-genotype effects on lipid levels can change with age in males: A longitudinal analysis. Am J Hum Genet. 1997; 61 (1) : 171-81. Epub 1997/07/01. doi: S0002-9297 (07) 64289-X [pii] doi: 10.1086/513902 PMID: 9245998; PubMed Central PMCID: PMC1715863.
66. Kulminski AM, Culminskaya I, Arbeev KG, Ukraintseva SV, Stallard E, Arbeeva L, et al. The role of lipid-related genes, aging-related processes, and environment in healthspan. Aging Cell. 2013; 12 (2) : 237-46. Epub 2013/01/17. doi: 10.1111/acel.12046 PMID: 23320904; PubMed Central PMCID: PMC3602307.
67. Williams GC. Pleiotropy, Natural-Selection, and the Evolution of Senescence. Evolution. 1957; 11 (4) : 398-411. PMID: ISI: A1957XE15100002.
68. Yashin AI, Wu D, Arbeev KG, Ukraintseva SV. Polygenic Effects of Common Single-Nucleotide Polymorphisms on Life Span: When Association Meets Causality. Rejuvenation Res. 2012. Epub 2012/04/27. doi: 10.1089/rej.2011.1257 PMID: 22533364.
69. Day-Williams AG, Zeggini E. The effect of next-generation sequencing technology on complex trait research. Eur J Clin Invest. 2011; 41 (5) : 561-7. Epub 2010/12/16. doi: 10.1111/j.1365-2362.2010. 02437.x PMID: 21155765; PubMed Central PMCID: PMC3107422.
70. McClellan J, King MC. Genetic heterogeneity in human disease. Cell. 2010; 141 (2) : 210-7. Epub 2010/04/21. doi: S0092-8674 (10) 00320-X [pii] doi: 10.1016/j.cell.2010.03.032 PMID: 20403315.
71. Neale BM, Sham PC. The future of association studies: Gene-based analysis and replication. Am J Hum Genet. 2004; 75 (3) : 353-62. Epub 2004/07/24. doi: 10.1086/423901 S0002-9297 (07) 63308-4 [pii]. PMID: 15272419; PubMed Central PMCID: PMC1182015.
72. Govindaraju DR, Cupples LA, Kannel WB, O'Donnell CJ, Atwood LD, D'Agostino RB Sr., et al. Genetics of the Framingham Heart Study population. Adv Genet. 2008; 62: 33-65. Epub 2008/11/18. doi: S0065- 2660 (08) 00602-0 [pii] doi: 10.1016/S0065-2660 (08) 00602-0 PMID: 19010253.
73. Splansky GL, Corey D, Yang Q, Atwood LD, Cupples LA, Benjamin EJ, et al. The Third Generation Cohort of the National Heart, Lung, and Blood Institute's Framingham Heart Study: Design, recruitment, and initial examination. Am J Epidemiol. 2007; 165 (11) : 1328-35. Epub 2007/03/21. doi: Kwm021 [pii] 10.1093/aje/kwm021. PMID: 17372189.
74. Cupples LA, Heard-Costa N, Lee M, Atwood LD. Genetics Analysis Workshop 16 Problem 2: The Framingham Heart Study data. BMC Proc. 2009; 3 Suppl 7: S3. Epub 2009/12/19. PMID: 20018020; PubMed Central PMCID: PMC2795927.
75. Lahoz C, Schaefer EJ, Cupples LA, Wilson PW, Levy D, Osgood D, et al. Apolipoprotein E genotype and cardiovascular disease in the Framingham Heart Study. Atherosclerosis. 2001; 154 (3) : 529-37. PMID: 11257253.
76. Myers RH, Schaefer EJ, Wilson PW, D'Agostino R, Ordovas JM, Espino A, et al. Apolipoprotein E epsilon4 association with dementia in a population-based study: The Framingham study. Neurology. 1996; 46 (3) : 673-7. PMID: 8618665.
77. Shi G, Rice TK, Gu CC, Rao DC. Application of three-level linear mixed-effects model incorporating gene-age interactions for association analysis of longitudinal family data. BMC Proc. 2009; 3 Suppl 7: S89. Epub 2009/12/19. PMID: 20018085; PubMed Central PMCID: PMC2795992.
78. Ikram MA, Seshadri S, Bis JC, Fornage M, DeStefano AL, Aulchenko YS, et al. Genomewide association studies of stroke. N Engl J Med. 2009; 360 (17) : 1718-28. Epub 2009/04/17. doi: NEJMoa0900094 [pii] doi: 10.1056/NEJMoa0900094 PMID: 19369658; PubMed Central PMCID: PMC2768348.
79. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002; 21 (11) : 1539-58. Epub 2002/07/12. doi: 10.1002/sim.1186 PMID: 12111919.
80. Sidhu D, Naugler C. Fasting time and lipid levels in a community-based population: A cross-sectional study. Arch Intern Med. 2012; 172 (22) : 1707-10. Epub 2012/11/14. doi: 1391022 [pii] doi: 10.1001/archinternmed.2012.3708 PMID: 23147400.
81. Port SC, Boyle NG, Hsueh WA, Quinones MJ, Jennrich RI, Goodarzi MO. The predictive role of blood glucose for mortality in subjects with cardiovascular disease. Am J Epidemiol. 2006; 163 (4) : 342-51. PMID: 16373527.
82. Yashin AI, Arbeev KG, Wu D, Arbeeva LS, Kulminski AM, Akushevich I, et al. How the quality of GWAS of human lifespan and health span can be improved. Front Genet. 2013; 4: 125. Epub 2013/07/05. doi: 10.3389/fgene.2013.00125 PMID: 23825477; PubMed Central PMCID: PMC3695378.