Disease risk factors identified through shared genetic architecture and electronic medical records

Science Translational Medicine

Volumn 6, Issue 234, 2014, Pages

  Li, Li ^a,b   Ruau, David J ^a,b   Patel, Chirag J ^a,b   Weber, Susan C ^a   Chen, Rong ^a,c   Tatonetti, Nicholas P ^d   Dudley, Joel T ^e   Butte, Atul J ^a,b  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b LUCILE PACKARD CHILDREN S HOSPITAL   (United States)

^c Personalis   (United States)

^d Och Spine at New York Presbyterian Hospitals   (United States)

^e MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALKALINE PHOSPHATASE; CHOLESTEROL; MAGNESIUM; PROSTATE SPECIFIC ANTIGEN;

ACUTE LYMPHOBLASTIC LEUKEMIA; ADULT; ALCOHOLISM; ALKALINE PHOSPHATASE BLOOD LEVEL; ARTICLE; C12ORF51 GENE; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; DISEASE ASSOCIATION; ELECTRONIC MEDICAL RECORD; FEMALE; GENE; GENETIC ASSOCIATION; GENETIC DATABASE; GENETIC TRAIT; GENETIC VARIABILITY; HUMAN; IKZF1 GENE; LUNG CANCER; MAGNESIUM BLOOD LEVEL; MAJOR CLINICAL STUDY; MALE; MEAN CORPUSCULAR VOLUME; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROGNOSIS; RISK FACTOR; STOMACH CANCER; THROMBOCYTE COUNT; VALIDATION STUDY; VENOUS THROMBOEMBOLISM; BIOLOGICAL MODEL; PROCEDURES;

ELECTRONIC HEALTH RECORDS; GENOME-WIDE ASSOCIATION STUDY; HUMANS; MODELS, BIOLOGICAL; RISK FACTORS;

EID: 84899859780     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.3007191     Document Type: Article

References (127)

1. Wellcome Trust Case Control Consortium, Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447, 661-678 (2007).
2. A. D. Johnson, C. J. O'Donnell, An open access database of genome-wide association results. BMC Med. Genet. 10, 6 (2009).
3. U. P. Steinbrecher, M. Lougheed, Scavenger receptor-independent stimulation of cholesterol esterification in macrophages by low density lipoprotein extracted from human aortic intima. Arterioscler. Thromb. 12, 608-625 (1992).
4. L. A. Hindorff, P. Sethupathy, H. A. Junkins, E. M. Ramos, J. P. Mehta, F. S. Collins, T. A. Manolio, Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc. Natl. Acad. Sci. U.S.A. 106, 9362-9367 (2009).
5. H. Li, Y. Lee, J. L. Chen, E. Rebman, J. Li, Y. A. Lussier, Complex-disease networks of trait-associated single-nucleotide polymorphisms (SNPs) unveiled by information theory. J. Am. Med. Inform. Assoc. 19, 295-305 (2012).
6. M. Sirota, M. A. Schaub, S. Batzoglou, W. H. Robinson, A. J. Butte, Autoimmune disease classification by inverse association with SNP alleles. PLOS Genet. 5, e1000792 (2009).
7. K. I. Goh, M. E. Cusick, D. Valle, B. Childs, M. Vidal, A. L. Barabási, The human disease network. Proc. Natl. Acad. Sci. U.S.A. 104, 8685-8690 (2007).
8. L. Li, D. Ruau, R. Chen, S. Weber, A. Butte, Systematic identification of risk factors for Alzheimer's disease through shared genetic architecture and electronic medical records. Pac. Symp. Biocomput. 18, 224-235 (2013).
9. E. A. Ashley, A. J. Butte, M. T. Wheeler, R. Chen, T. E. Klein, F. E. Dewey, J. T. Dudley, K. E. Ormond, A. Pavlovic, A. A. Morgan, D. Pushkarev, N. F. Neff, L. Hudgins, L. Gong, L. M. Hodges, D. S. Berlin, C. F. Thorn, K. Sangkuhl, J. M. Hebert, M. Woon, H. Sagreiya, R. Whaley, J. W. Knowles, M. F. Chou, J. V. Thakuria, A. M. Rosenbaum, A. W. Zaranek, G. M. Church, H. T. Greely, S. R. Quake, R. B. Altman, Clinical assessment incorporating a personal genome. Lancet 375, 1525-1535 (2010).
10. R. Chen, E. Corona, M. Sikora, J. T. Dudley, A. A. Morgan, A. Moreno-Estrada, G. B. Nilsen, D. Ruau, S. E. Lincoln, C. D. Bustamante, A. J. Butte, Type 2 diabetes risk alleles demonstrate extreme directional differentiation among human populations, compared to other diseases. PLOS Genet. 8, e1002621 (2012).
11. R. Chen, E. V. Davydov, M. Sirota, A. J. Butte, Non-synonymous and synonymous coding SNPs show similar likelihood and effect size of human disease association. PLOS One 5, e13574 (2010).
12. C. J. Patel, R. Chen, A. J. Butte, Data-driven integration of epidemiological and toxicological data to select candidate interacting genes and environmental factors in association with disease. Bioinformatics 28, i121-i126 (2012).
13. S. Suthram, J. T. Dudley, A. P. Chiang, R. Chen, T. J. Hastie, A. J. Butte, Network-based elucidation of human disease similarities reveals common functional modules enriched for pluripotent drug targets. PLOS Comput. Biol. 6, e1000662 (2010).
14. F. E. Dewey, R. Chen, S. P. Cordero, K. E. Ormond, C. Caleshu, K. J. Karczewski, M. Whirl-Carrillo, M. T. Wheeler, J. T. Dudley, J. K. Byrnes, O. E. Cornejo, J. W. Knowles, M. Woon, K. Sangkuhl, L. Gong, C. F. Thorn, J. M. Hebert, E. Capriotti, S. P. David, A. Pavlovic, A. West, J. V. Thakuria, M. P. Ball, A. W. Zaranek, H. L. Rehm, G. M. Church, J. S. West, C. D. Bustamante, M. Snyder, R. B. Altman, T. E. Klein, A. J. Butte, E. A. Ashley, Phased whole-genome genetic risk in a family quartet using a major allele reference sequence. PLOS Genet. 7, e1002280 (2011).
15. M. H. Cho, P. J. Castaldi, E. S. Wan, M. Siedlinski, C. P. Hersh, D. L. Demeo, B. E. Himes, J. S. Sylvia, B. J. Klanderman, J. P. Ziniti, C. Lange, A. A. Litonjua, D. Sparrow, E. A. Regan, B. J. Make, J. E. Hokanson, T. Murray, J. B. Hetmanski, S. G. Pillai, X. Kong, W. H. Anderson, R. Tal-Singer, D. A. Lomas, H. O. Coxson, L. D. Edwards, W. MacNee, J. Vestbo, J. C. Yates, A. Agusti, P. M. Calverley, B. Celli, C. Crim, S. Rennard, E. Wouters, P. Bakke, A. Gulsvik, J. D. Crapo, T. H. Beaty, E. K. Silverman, A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13. Hum. Mol. Genet. 21, 947-957 (2012).
16. S. G. Pillai, X. Kong, L. D. Edwards, M. H. Cho, W. H. Anderson, H. O. Coxson, D. A. Lomas, E. K. Silverman; ECLIPSE and ICGN Investigators, Loci identified by genome-wide association studies influence different disease-related phenotypes in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 182, 1498-1505 (2010).
17. J. Wang, M. R. Spitz, C. I. Amos, A. V. Wilkinson, X. Wu, S. Shete, Mediating effects of smoking and chronic obstructive pulmonary disease on the relation between the CHRNA5-A3 genetic locus and lung cancer risk. Cancer 116, 3458-3462 (2010).
18. M. H. Cho, N. Boutaoui, B. J. Klanderman, J. S. Sylvia, J. P. Ziniti, C. P. Hersh, D. L. DeMeo, G. M. Hunninghake, A. A. Litonjua, D. Sparrow, C. Lange, S. Won, J. R. Murphy, T. H. Beaty, E. A. Regan, B. J. Make, J. E. Hokanson, J. D. Crapo, X. Kong, W. H. Anderson, R. Tal-Singer, D. A. Lomas, P. Bakke, A. Gulsvik, S. G. Pillai, E. K. Silverman, Variants in FAM13A are associated with chronic obstructive pulmonary disease. Nat. Genet. 42, 200-202 (2010).
19. D. Lambrechts, I. Buysschaert, P. Zanen, J. Coolen, N. Lays, H. Cuppens, H. J. Groen, W. Dewever, R. J. van Klaveren, J. Verschakelen, C. Wijmenga, D. S. Postma, M. Decramer, W. Janssens, The 15q24/25 susceptibility variant for lung cancer and chronic obstructive pulmonary disease is associated with emphysema. Am. J. Respir. Crit. Care Med. 181, 486-493 (2010).
20. S. G. Pillai, D. Ge, G. Zhu, X. Kong, K. V. Shianna, A. C. Need, S. Feng, C. P. Hersh, P. Bakke, A. Gulsvik, A. Ruppert, K. C. Lødrup Carlsen, A. Roses, W. Anderson, S. I. Rennard, D. A. Lomas, E. K. Silverman, D. B. Goldstein; ICGN Investigators, A genome-wide association study in chronic obstructive pulmonary disease (COPD): Identification of two major susceptibility loci. PLOS Genet. 5, e1000421 (2009).
21. J. Vestbo, S. S. Hurd, A. G. Agustí, P. W. Jones, C. Vogelmeier, A. Anzueto, P. J. Barnes, L. M. Fabbri, F. J. Martinez, M. Nishimura, R. A. Stockley, D. D. Sin, R. Rodriguez-Roisin, Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am. J. Respir. Crit. Care Med. 187, 347-365 (2013).
22. Centers for Disease Control and Prevention, The Health Consequences of Smoking: A Report of the Surgeon General (Centers for Disease Control and Prevention, Atlanta, GA, 2004).
23. R. A. Pauwels, A. S. Buist, P. M. Calverley, C. R. Jenkins, S. S. Hurd; GOLD Scientific Committee, Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. Am. J. Respir. Crit. Care Med. 163, 1256-1276 (2001).
24. E. Png, A. Thalamuthu, R. T. Ong, H. Snippe, G. J. Boland, M. Seielstad, A genome-wide association study of hepatitis B vaccine response in an Indonesian population reveals multiple independent risk variants in the HLA region. Hum. Mol. Genet. 20, 3893-3898 (2011).
25. N. Kato, F. Takeuchi, Y. Tabara, T. N. Kelly, M. J. Go, X. Sim, W. T. Tay, C. H. Chen, Y. Zhang, K. Yamamoto, T. Katsuya, M. Yokota, Y. J. Kim, R. T. Ong, T. Nabika, D. Gu, L. C. Chang, Y. Kokubo, W. Huang, K. Ohnaka, Y. Yamori, E. Nakashima, C. E. Jaquish, J. Y. Lee, M. Seielstad, M. Isono, J. E. Hixson, Y. T. Chen, T. Miki, X. Zhou, T. Sugiyama, J. P. Jeon, J. J. Liu, R. Takayanagi, S. S. Kim, T. Aung, Y. J. Sung, X. Zhang, T. Y. Wong, B. G. Han, S. Kobayashi, T. Ogihara, D. Zhu, N. Iwai, J. Y. Wu, Y. Y. Teo, E. S. Tai, Y. S. Cho, J. He, Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east Asians. Nat. Genet. 43, 531-538 (2011).
26. Y. J. Kim, M. J. Go, C. Hu, C. B. Hong, Y. K. Kim, J. Y. Lee, J. Y. Hwang, J. H. Oh, D. J. Kim, N. H. Kim, S. Kim, E. J. Hong, J. H. Kim, H. Min, Y. Kim, R. Zhang, W. Jia, Y. Okada, A. Takahashi, M. Kubo, T. Tanaka, N. Kamatani, K. Matsuda; MAGIC consortium, T. Park, B. Oh, K. Kimm, D. Kang, C. Shin, N. H. Cho, H. L. Kim, B. G. Han, Y. S. Cho, Large-scale genome-wide association studies in East Asians identify new genetic loci influencing metabolic traits. Nat. Genet. 43, 990-995 (2011).
27. Y. Kamatani, K. Matsuda, Y. Okada, M. Kubo, N. Hosono, Y. Daigo, Y. Nakamura, N. Kamatani, Genome-wide association study of hematological and biochemical traits in a Japanese population. Nat. Genet. 42, 210-215 (2010).
28. K. G. Kahl, W. Greggersen, U. Schweiger, J. Cordes, C. U. Correll, J. Ristow, J. Burow, C. Findel, A. Stoll, C. Balijepalli, L. Göres, C. Lösch, T. Hillemacher, S. Bleich, S. Moebus, Prevalence of the metabolic syndrome in men and women with alcohol dependence: Results from a cross-sectional study during behavioural treatment in a controlled environment. Addiction 105, 1921-1927 (2010).
29. G. A. Gross, Drug and alcohol abuse and cholesterol levels. J. Am. Osteopath. Assoc. 94, 55-56, 61-62 (1994).
30. A. Imhof, M. Froehlich, H. Brenner, H. Boeing, M. B. Pepys, W. Koenig, Effect of alcohol consumption on systemic markers of inflammation. Lancet 357, 763-767 (2001).
31. H. J. Lowe, T. A. Ferris, P. M. Hernandez, S. C. Weber, STRIDE - An integrated standards-based translational research informatics platform. AMIA Annu. Symp. Proc. 2009, 391-395 (2009).
32. P. W. Wilson, R. B. D'Agostino, D. Levy, A. M. Belanger, H. Silbershatz, W. B. Kannel, Prediction of coronary heart disease using risk factor categories. Circulation 97, 1837-1847 (1998).
33. E. Zeggini, M. N. Weedon, C. M. Lindgren, T. M. Frayling, K. S. Elliott, H. Lango, N. J. Timpson, J. R. Perry, N. W. Rayner, R. M. Freathy, J. C. Barrett, B. Shields, A. P. Morris, S. Ellard, C. J. Groves, L. W. Harries, J. L. Marchini, K. R. Owen, B. Knight, L. R. Cardon, M. Walker, G. A. Hitman, A. D. Morris, A. S. Doney; Wellcome Trust Case Control Consortium (WTCCC), M. I. McCarthy, A. T. Hattersley, Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 316, 1336-1341 (2007).
34. T. M. Frayling, N. J. Timpson, M. N. Weedon, E. Zeggini, R. M. Freathy, C. M. Lindgren, J. R. Perry, K. S. Elliott, H. Lango, N. W. Rayner, B. Shields, L. W. Harries, J. C. Barrett, S. Ellard, C. J. Groves, B. Knight, A. M. Patch, A. R. Ness, S. Ebrahim, D. A. Lawlor, S. M. Ring, Y. Ben-Shlomo, M. R. Jarvelin, U. Sovio, A. J. Bennett, D. Melzer, L. Ferrucci, R. J. Loos, I. Barroso, N. J. Wareham, F. Karpe, K. R. Owen, L. R. Cardon, M. Walker, G. A. Hitman, C. N. Palmer, A. S. Doney, A. D. Morris, G. D. Smith, A. T. Hattersley, M. I. McCarthy, A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316, 889-894 (2007).
35. T. A. Manolio, F. S. Collins, N. J. Cox, D. B. Goldstein, L. A. Hindorff, D. J. Hunter, M. I. McCarthy, E. M. Ramos, L. R. Cardon, A. Chakravarti, J. H. Cho, A. E. Guttmacher, A. Kong, L. Kruglyak, E. Mardis, C. N. Rotimi, M. Slatkin, D. Valle, A. S. Whittemore, M. Boehnke, A. G. Clark, E. E. Eichler, G. Gibson, J. L. Haines, T. F. Mackay, S. A. McCarroll, P. M. Visscher, Finding the missing heritability of complex diseases. Nature 461, 747-753 (2009).
36. S. C. Harrison, M. V. Holmes, S. E. Humphries, Mendelian randomisation, lipids, and cardiovascular disease. Lancet 380, 543-545 (2012).
37. N. A. Sheehan, V. Didelez, P. R. Burton, M. D. Tobin, Mendelian randomisation and causal inference in observational epidemiology. PLOS Med. 5, e177 (2008).
38. G. D. Smith, S. Ebrahim, 'Mendelian randomization': Can genetic epidemiology contribute to understanding environmental determinants of disease? Int. J. Epidemiol. 32, 1-22 (2003).
39. B. F. Voight, G. M. Peloso, M. Orho-Melander, R. Frikke-Schmidt, M. Barbalic, M. K. Jensen, G. Hindy, H. Hólm, E. L. Ding, T. Johnson, H. Schunkert, N. J. Samani, R. Clarke, J. C. Hopewell, J. F. Thompson, M. Li, G. Thorleifsson, C. Newton-Cheh, K. Musunuru, J. P. Pirruccello, D. Saleheen, L. Chen, A. Stewart, A. Schillert, U. Thorsteinsdottir, G. Thorgeirsson, S. Anand, J. C. Engert, T. Morgan, J. Spertus, M. Stoll, K. Berger, N. Martinelli, D. Girelli, P. P. McKeown, C. C. Patterson, S. E. Epstein, J. Devaney, M. S. Burnett, V. Mooser, S. Ripatti, I. Surakka, M. S. Nieminen, J. Sinisalo, M. L. Lokki, M. Perola, A. Havulinna, U. de Faire, B. Gigante, E. Ingelsson, T. Zeller, P. Wild, P. I. de Bakker, O. H. Klungel, A. H. Maitland-van der Zee, B. J. Peters, A. de Boer, D. E. Grobbee, P. W. Kamphuisen, V. H. Deneer, C. C. Elbers, N. C. Onland-Moret, M. H. Hofker, C. Wijmenga, W. M. Verschuren, J. M. Boer, Y. T. van der Schouw, A. Rasheed, P. Frossard, S. Demissie, C. Willer, R. Do, J. M. Ordovas, G. R. Abecasis, M. Boehnke, K. L. Mohlke, M. J. Daly, C. Guiducci, N. P. Burtt, A. Surti, E. Gonzalez, S. Purcell, S. Gabriel, J. Marrugat, J. Peden, J. Erdmann, P. Diemert, C. Willenborg, I. R. König, M. Fischer, C. Hengstenberg, A. Ziegler, I. Buysschaert, D. Lambrechts, F. Van de Werf, K. A. Fox, N. E. El Mokhtari, D. Rubin, J. Schrezenmeir, S. Schreiber, A. Schäfer, J. Danesh, S. Blankenberg, R. Roberts, R. McPherson, H. Watkins, A. S. Hall, K. Overvad, E. Rimm, E. Boerwinkle, A. Tybjaerg-Hansen, L. A. Cupples, M. P. Reilly, O. Melander, P. M. Mannucci, D. Ardissino, D. Siscovick, R. Elosua, K. Stefansson, C. J. O'Donnell, V. Salomaa, D. J. Rader, L. Peltonen, S. M. Schwartz, D. Altshuler, S. Kathiresan, Plasma HDL cholesterol and risk of myocardial infarction: A mendelian randomisation study. Lancet 380, 572-580 (2012).
40. J. C. Denny, D. C. Crawford, M. D. Ritchie, S. J. Bielinski, M. A. Basford, Y. Bradford, H. S. Chai, L. Bastarache, R. Zuvich, P. Peissig, D. Carrell, A. H. Ramirez, J. Pathak, R. A. Wilke, L. Rasmussen, X. Wang, J. A. Pacheco, A. N. Kho, M. G. Hayes, N. Weston, M. Matsumoto, P. A. Kopp, K. M. Newton, G. P. Jarvik, R. Li, T. A. Manolio, I. J. Kullo, C. G. Chute, R. L. Chisholm, E. B. Larson, C. A. McCarty, D. R. Masys, D. M. Roden, M. de Andrade, Variants near FOXE1 are associated with hypothyroidism and other thyroid conditions: Using electronic medical records for genome- and phenome-wide studies. Am. J. Hum. Genet. 89, 529-542 (2011).
41. K. D. Mandl, I. S. Kohane, Escaping the EHR trap - The future of health IT. N. Engl. J. Med. 366, 2240-2242 (2012).
42. A. N. Kho, J. A. Pacheco, P. L. Peissig, L. Rasmussen, K. M. Newton, N. Weston, P. K. Crane, J. Pathak, C. G. Chute, S. J. Bielinski, I. J. Kullo, R. Li, T. A. Manolio, R. L. Chisholm, J. C. Denny, Electronic medical records for genetic research: Results of the eMERGE consortium. Sci. Transl. Med. 3, 79re1 (2011).
43. D. Westreich, Berkson's bias, selection bias, and missing data. Epidemiology 23, 159-164 (2012).
44. J. Ott, Y. Kamatani, M. Lathrop, Family-based designs for genome-wide association studies. Nat. Rev. Genet. 12, 465-474 (2011).
45. R. Chen, L. Li, A. J. Butte, AILUN: Reannotating gene expression data automatically. Nat. Methods 4, 879 (2007).
46. H. C. Wu, R. W. P. Luk, K. F. Wong, K. L. Kwok, Interpreting TF-IDF term weights as making relevance decisions. ACM Trans. Inform. Syst. 26, Article No. 13 (2008).
47. J. D. Storey, R. Tibshirani, Statistical significance for genomewide studies. Proc. Natl. Acad. Sci. U.S.A. 100, 9440-9445 (2003).
48. P. Shannon, A. Markiel, O. Ozier, N. S. Baliga, J. T. Wang, D. Ramage, N. Amin, B. Schwikowski, T. Ideker, Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498-2504 (2003).
49. L. Royer, M. Reimann, B. Andreopoulos, M. Schroeder, Unraveling protein networks with power graph analysis. PLOS Comput. Biol. 4, e1000108 (2008).
50. R. Ihaka, R. Gentleman, R: A language for data analysis and graphics. J. Comput. Graphic. Stat. 5, 299-314 (1996).
51. D. J. Tobin, N. Orentreich, D. A. Fenton, J. C. Bystryn, Antibodies to hair follicles in alopecia areata. J. Invest. Dermatol. 102, 721-724 (1994).
52. P. Caramelli, R. Nitrini, R. Maranhao, A. C. Lourenco, M. C. Damasceno, C. Vinagre, B. Caramelli, Increased apolipoprotein B serum concentration in Alzheimer's disease. Acta Neurol. Scand. 100, 61-63 (1999).
53. S. E. O'Bryant, S. C. Waring, V. Hobson, J. R. Hall, C. B. Moore, T. Bottiglieri, P. Massman, R. Diaz-Arrastia, Decreased C-reactive protein levels in Alzheimer disease. J. Geriatr. Psychiatry Neurol. 23, 49-53 (2010).
54. T. Matsuzaki, K. Sasaki, J. Hata, Y. Hirakawa, K. Fujimi, T. Ninomiya, S. O. Suzuki, S. Kanba, Y. Kiyohara, T. Iwaki, Association of Alzheimer disease pathology with abnormal lipid metabolism: The Hisayama Study. Neurology 77, 1068-1075 (2011).
55. G. T. Lesser, V. Haroutunian, D. P. Purohit, M. Schnaider Beeri, J. Schmeidler, L. Honkanen, R. Neufeld, L. S. Libow, Serum lipids are related to Alzheimer's pathology in nursing home residents. Dement. Geriatr. Cogn. Disord. 27, 42-49 (2009).
56. M. van Oijen, I. M. van der Meer, A. Hofman, J. C. Witteman, P. J. Koudstaal, M. M. Breteler, Lipoprotein-associated phospholipase A2 is associated with risk of dementia. Ann. Neurol. 59, 139-144 (2006).
57. J. H. Ringrose, HLA-B27 associated spondyloarthropathy, an autoimmune disease based on crossreactivity between bacteria and HLA-B27? Ann. Rheum. Dis. 58, 598-610 (1999).
58. D. H. Bryant, M. W. Burns, L. Lazarus, The correlation between skin tests, bronchial provocation tests and the serum level of IgE specific for common allergens in patients with asthma. Clin. Allergy 5, 145-157 (1975).
59. V. P. Chinem, H. A. Miot, Prevalence of actinic skin lesions in patients with basal cell carcinoma of the head: A case-control study. Rev. Assoc. Med. Bras. 58, 188-196 (2012).
60. R. Zanetti, S. Rosso, C. Martinez, A. Nieto, A. Miranda, M. Mercier, D. I. Loria, A. Østerlind, R. Greinert, C. Navarro, G. Fabbrocini, C. Barbera, H. Sancho-Garnier, L. Gafà, A. Chiarugi, R. Mossotti, Comparison of risk patterns in carcinoma and melanoma of the skin in men: A multi-centre case-case-control study. Br. J. Cancer 94, 743-751 (2006).
61. A. Kikuchi, H. Shimizu, T. Nishikawa, Clinical histopathological characteristics of basal cell carcinoma in Japanese patients. Arch. Dermatol. 132, 320-324 (1996).
62. K. M. Musallam, V. G. Sankaran, M. D. Cappellini, L. Duca, D. G. Nathan, A. T. Taher, Fetal hemoglobin levels and morbidity in untransfused patients with β-thalassemia intermedia. Blood 119, 364-367 (2012).
63. M. M. Kaplan, M. E. Gershwin, Primary biliary cirrhosis. N. Engl. J. Med. 353, 1261-1273 (2005).
64. E. Emanuele, M. V. Carlin, A. D'Angelo, E. Peros, F. Barale, D. Geroldi, P. Politi, Elevated plasma levels of lipoprotein(a) in psychiatric patients: A possible contribution to increased vascular risk. Eur. Psychiatry 21, 129-133 (2006).
65. M. Sagud, A. Mihaljevic-Peles, N. Pivac, M. Jakovljevic, D. Muck-Seler, Lipid levels in female patients with affective disorders. Psychiatry Res. 168, 218-221 (2009).
66. V. M. Villarejos, J. Serra, K. A. Visoná, C. E. Eduarte, Antibodies to single stranded DNA: A diagnostic aid in chronic hepatitis B virus infections. J. Med. Virol. 4, 97-101 (1979).
67. M. Benn, Apolipoprotein B levels, APOB alleles, and risk of ischemic cardiovascular disease in the general population, a review. Atherosclerosis 206, 17-30 (2009).
68. G. W. Burggraf, J. O. Parker, Prognosis in coronary artery disease. Angiographic, hemodynamic, and clinical factors. Circulation 51, 146-156 (1975).
69. M. P. Reilly, M. L. Wolfe, J. Dykhouse, K. Reddy, A. R. Localio, D. J. Rader, Intercellular adhesion molecule 1 (ICAM-1) gene variant is associated with coronary artery calcification independent of soluble ICAM-1 levels. J. Investig. Med. 52, 515-522 (2004).
70. C. J. Packard, D. S. O'Reilly, M. J. Caslake, A. D. McMahon, I. Ford, J. Cooney, C. H. Macphee, K. E. Suckling, M. Krishna, F. E. Wilkinson, A. Rumley, G. D. Lowe, Lipoprotein-associated phospholipase A2 as an independent predictor of coronary heart disease. West of Scotland Coronary Prevention Study Group. N. Engl. J. Med. 343, 1148-1155 (2000).
71. K. Vikenes, M. Farstad, J. E. Nordrehaug, Serotonin is associated with coronary artery disease and cardiac events. Circulation 100, 483-489 (1999).
72. A. Sako, J. Kitayama, S. Kaisaki, H. Nagawa, Hyperlipidemia is a risk factor for lymphatic metastasis in superficial esophageal carcinoma. Cancer Lett. 208, 43-49 (2004).
73. M. A. Martínez-García, M. Luque-Ramírez, J. L. San-Millán, H. F. Escobar-Morreale, Body iron stores and glucose intolerance in premenopausal women: Role of hyperandrogenism, insulin resistance, and genomic variants related to inflammation, oxidative stress, and iron metabolism. Diabetes Care 32, 1525-1530 (2009).
74. S. Haghighi, M. Amini, Z. Pournaghshband, P. Amini, S. Hovsepian, Relationship between gamma-glutamyl transferase and glucose intolerance in first degree relatives of type 2 diabetics patients. J. Res. Med. Sci. 16, 123-129 (2011).
75. R. R. Little, J. D. England, H. M. Wiedmeyer, E. M. McKenzie, D. J. Pettitt, W. C. Knowler, D. E. Goldstein, Relationship of glycosylated hemoglobin to oral glucose tolerance. Implications for diabetes screening. Diabetes 37, 60-64 (1988).
76. J. D. McGarry, Disordered metabolism in diabetes: Have we underemphasized the fat component? J. Cell. Biochem. 55, 29-38 (1994).
77. F. Fumeron, F. Péan, F. Driss, B. Balkau, J. Tichet, M. Marre, B. Grandchamp; Insulin Resistance Syndrome (DESIR) Study Group, Ferritin and transferrin are both predictive of the onset of hyperglycemia in men and women over 3 years: The data from an epidemiological study on the Insulin Resistance Syndrome (DESIR) study. Diabetes Care 29, 2090-2094 (2006).
78. Y. Urwijitaroon, S. Barusrux, A. Romphruk, C. Puapairoj, P. Thongkrajai, Anti-HIV antibody titer: An alternative supplementary test for diagnosis of HIV-1 infection. Asian Pac. J. Allergy Immunol. 15, 193-198 (1997).
79. A. V. Chobanian, G. L. Bakris, H. R. Black, W. C. Cushman, L. A. Green, J. L. Izzo Jr., D. W. Jones, B. J. Materson, S. Oparil, J. T. Wright Jr., E. J. Roccella; Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee, Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 42, 1206-1252 (2003).
80. J. Coresh, G. L. Wei, G. McQuillan, F. L. Brancati, A. S. Levey, C. Jones, M. J. Klag, Prevalence of high blood pressure and elevated serum creatinine level in the United States: Findings from the third National Health and Nutrition Examination Survey (1988-1994). Arch. Intern. Med. 161, 1207-1216 (2001).
81. M. K. Kim, K. H. Baek, K. H. Song, M. I. Kang, J. H. Choi, J. C. Bae, C. Y. Park, W. Y. Lee, K. W. Oh, Increased serum ferritin predicts the development of hypertension among middle-aged men. Am. J. Hypertension 25, 492-497 (2012).
82. M. Cirillo, M. Laurenzi, M. Trevisan, J. Stamler, Hematocrit, blood pressure, and hypertension. The Gubbio Population Study. Hypertension 20, 319-326 (1992).
83. G. F. Strippoli, J. C. Craig, C. Manno, F. P. Schena, Hemoglobin targets for the anemia of chronic kidney disease: A meta-analysis of randomized, controlled trials. J. Am. Soc. Nephrol. 15, 3154-3165 (2004).
84. K. Sutton-Tyrrell, A. Bostom, J. Selhub, C. Zeigler-Johnson, High homocysteine levels are independently related to isolated systolic hypertension in older adults. Circulation 96, 1745-1749 (1997).
85. R. Rahim, K. Nahar, I. A. Khan, Platelet count in 100 cases of pregnancy induced hypertension. Mymensingh Med. J. 19, 5-9 (2010).
86. S. M. Dogan, M. Aydin, M. Gursurer, A. Dursun, G. Mungan, T. Onuk, N-terminal probrain natriuretic peptide predicts altered circadian variation in essential hypertension. Coron. Artery Dis. 18, 347-352 (2007).
87. D. J. Buchan, Diagnosis and management of inflammatory bowel disease. Can. Fam. Physician 22, 47-51 (1976).
88. A. D. Pradhan, J. E. Manson, N. Rifai, J. E. Buring, P. M. Ridker, C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 286, 327-334 (2001).
89. M. W. Mansfield, D. M. Heywood, P. J. Grant, Circulating levels of factor VII, fibrinogen, and von Willebrand factor and features of insulin resistance in first-degree relatives of patients with NIDDM. Circulation 94, 2171-2176 (1996).
90. A. Borai, C. Livingstone, F. Abdelaal, A. Bawazeer, V. Keti, G. Ferns, The relationship between glycosylated haemoglobin (HbA1c) and measures of insulin resistance across a range of glucose tolerance. Scand. J. Clin. Lab. Invest. 71, 168-172 (2011).
91. A. Laws, G. M. Reaven, Evidence for an independent relationship between insulin resistance and fasting plasma HDL-cholesterol, triglyceride and insulin concentrations. J. Intern. Med. 231, 25-30 (1992).
92. T. L. Nelson, M. L. Biggs, J. R. Kizer, M. Cushman, J. E. Hokanson, C. D. Furberg, K. J. Mukamal, Lipoprotein-associated phospholipase A2 (Lp-PLA2) and future risk of type 2 diabetes: Results from the Cardiovascular Health Study. J. Clin. Endocrinol. Metab. 97, 1695-1701 (2012).
93. A. J. Hanley, R. D'Agostino Jr., L. E. Wagenknecht, M. F. Saad, P. J. Savage, R. Bergman, S. M. Haffner; Insulin Resistance Atherosclerosis Study, Increased proinsulin levels and decreased acute insulin response independently predict the incidence of type 2 diabetes in the insulin resistance atherosclerosis study. Diabetes 51, 1263-1270 (2002).
94. J. Bazelmans, P. J. Nestel, C. Nolan, Insulin-induced glucose utilization influences triglyceride metabolism. Clin. Sci. 64, 511-516 (1983).
95. J. C. Fink, R. A. Burdick, S. J. Kurth, S. A. Blahut, N. C. Armistead, M. S. Turner, L. M. Shickle, P. D. Light, Significance of serum creatinine values in new end-stage renal disease patients. Am. J. Kidney Dis. 34, 694-701 (1999).
96. S. A. Khuder, Effect of cigarette smoking on major histological types of lung cancer: A meta-analysis. Lung Cancer 31, 139-148 (2001).
97. E. A. Holly, D. A. Aston, R. D. Cress, D. K. Ahn, J. J. Kristiansen, Cutaneous melanoma in women. II. Phenotypic characteristics and other host-related factors. Am. J. Epidemiol. 141, 934-942 (1995).
98. M. A. Tucker, Melanoma epidemiology. Hematol. Oncol. Clin. North Am. 23, 383-395 (2009).
99. M. B. Veierød, E. Weiderpass, M. Thörn, J. Hansson, E. Lund, B. Armstrong, H. O. Adami, A prospective study of pigmentation, sun exposure, and risk of cutaneous malignant melanoma in women. J. Natl. Cancer Inst. 95, 1530-1538 (2003).
100. W. Yumura, S. Suganuma, K. Nitta, Y. Sano, K. Uchida, H. Nihei, Prolonged membranous lupus nephritis with change of anti-ssDNA antibody titer and repeated renal relapse. Clin. Exp. Nephrol. 8, 363-368 (2004).
101. J. Sierra-Johnson, V. K. Somers, F. H. Kuniyoshi, C. A. Garza, W. L. Isley, A. S. Gami, F. Lopez-Jimenez, Comparison of apolipoprotein-B/ apolipoprotein-AI in subjects with versus without the metabolic syndrome. Am. J. Cardiol. 98, 1369-1373 (2006).
102. M. Fröhlich, A. Imhof, G. Berg, W. L. Hutchinson, M. B. Pepys, H. Boeing, R. Muche, H. Brenner, W. Koenig, Association between C-reactive protein and features of the metabolic syndrome: A population-based study. Diabetes Care 23, 1835-1839 (2000).
103. T. Gombet, B. Longo-Mbenza, B. Ellenga-Mbolla, M. S. Ikama, E. Mokondjimobe, G. Kimbally-Kaky, J. L. Nkoua, Aging, female sex, migration, elevated HDL-C, and inflammation are associated with prevalence of metabolic syndrome among African bank employees. Int. J. Gen. Med. 5, 495-503 (2012).
104. H. P. Gong, Y. M. Du, L. N. Zhong, Z. Q. Dong, X. Wang, Y. J. Mao, Q. H. Lu, Plasma lipoprotein-associated phospholipase A2 in patients with metabolic syndrome and carotid atherosclerosis. Lipids Health Dis. 10, 13 (2011).
105. E. Burns, G. P. Mulley, Practical problems with eye-drops among elderly ophthalmology outpatients. Age Ageing 21, 168-170 (1992).
106. P. H. Lalive, T. Menge, C. Delarasse, B. Della Gaspera, D. Pham-Dinh, P. Villoslada, H. C. von Büdingen, C. P. Genain, Antibodies to native myelin oligodendrocyte glycoprotein are serologic markers of early inflammation in multiple sclerosis. Proc. Natl. Acad. Sci. U.S.A. 103, 2280-2285 (2006).
107. A. Brucato, R. Cimaz, R. Caporali, V. Ramoni, J. Buyon, Pregnancy outcomes in patients with autoimmune diseases and anti-Ro/SSA antibodies. Clin. Rev. Allergy Immunol. 40, 27-41 (2011).
108. T. S. Burgert, S. E. Taksali, J. Dziura, T. R. Goodman, C. W. Yeckel, X. Papademetris, R. T. Constable, R. Weiss, W. V. Tamborlane, M. Savoye, A. A. Seyal, S. Caprio, Alanine aminotransferase levels and fatty liver in childhood obesity: Associations with insulin resistance, adiponectin, and visceral fat. J. Clin. Endocrinol. Metab. 91, 4287-4294 (2006).
109. I. L. Mertens, L. F. Van Gaal, Overweight, obesity, and blood pressure: The effects of modest weight reduction. Obes. Res. 8, 270-278 (2000).
110. T. Kamoda, H. Saitoh, M. Inudoh, K. Miyazaki, A. Matsui, The serum levels of proinsulin and their relationship with IGFBP-1 in obese children. Diabetes Obes. Metab. 8, 192-196 (2006).
111. M. Nakamura, Y. Shimizu-Yoshida, Y. Takii, A. Komori, T. Yokoyama, T. Ueki, M. Daikoku, K. Yano, T. Matsumoto, K. Migita, H. Yatsuhashi, M. Ito, N. Masaki, H. Adachi, Y. Watanabe, Y. Nakamura, T. Saoshiro, T. Sodeyama, M. Koga, S. Shimoda, H. Ishibashi, Antibody titer to gp210-C terminal peptide as a clinical parameter for monitoring primary biliary cirrhosis. J. Hepatol. 42, 386-392 (2005).
112. D. S. Smith, P. A. Humphrey, W. J. Catalona, The early detection of prostate carcinoma with prostate specific antigen: The Washington University experience. Cancer 80, 1852-1856 (1997).
113. K. Egerer, E. Feist, G. R. Burmester, The serological diagnosis of rheumatoid arthritis: Antibodies to citrullinated antigens. Dtsch. Arztebl. Int. 106, 159-163 (2009).
114. L. S. Avnon, F. Manzur, A. Bolotin, D. Heimer, D. Flusser, D. Buskila, S. Sukenik, M. Abu-Shakra, Pulmonary functions testing in patients with rheumatoid arthritis. Isr. Med. Assoc. J. 11, 83-87 (2009).
115. J. M. Gill, A. M. Quisel, P. V. Rocca, D. T. Walters, Diagnosis of systemic lupus erythematosus. Am. Fam. Physician 68, 2179-2186 (2003).
116. Y. Morita, Y. Muro, K. Sugiura, Y. Tomita, Anti-cyclic citrullinated peptide antibody in systemic sclerosis. Clin. Exp. Rheumatol. 26, 542-547 (2008).
117. F. Vaziri-Sani, S. Oak, J. Radtke, K. Lernmark, K. Lynch, C. D. Agardh, C. M. Cilio, A. L. Lethagen, E. Ortqvist, M. Landin-Olsson, C. Törn, C. S. Hampe, ZnT8 autoantibody titers in type 1 diabetes patients decline rapidly after clinical onset. Autoimmunity 43, 598-606 (2010).
118. M. Rönnback, J. Fagerudd, C. Forsblom, K. Pettersson-Fernholm, A. Reunanen, P. H. Groop; Finnish Diabetic Nephropathy (FinnDiane) Study Group, Altered age-related blood pressure pattern in type 1 diabetes. Circulation 110, 1076-1082 (2004).
119. H. Gylling, J. A. Tuominen, V. A. Koivisto, T. A. Miettinen, Cholesterol metabolism in type 1 diabetes. Diabetes 53, 2217-2222 (2004).
120. J. Ma, A. Mollsten, M. Prazny, H. Falhammar, K. Brismar, G. Dahlquist, S. Efendic, H. F. Gu, Genetic influences of the intercellular adhesion molecule 1 (ICAM-1) gene polymorphisms in development of type 1 diabetes and diabetic nephropathy. Diabetic Med. 23, 1093-1099 (2006).
121. S. Li, H. J. Shin, E. L. Ding, R. M. van Dam, Adiponectin levels and risk of type 2 diabetes: A systematic review and meta-analysis. JAMA 302, 179-188 (2009).
122. A. D. Pradhan, J. E. Manson, J. B. Meigs, N. Rifai, J. E. Buring, S. Liu, P. M. Ridker, Insulin, proinsulin, proinsulin:insulin ratio, and the risk of developing type 2 diabetes mellitus in women. Am. J. Med. 114, 438-444 (2003).
123. J. A. Chirinos, G. A. Heresi, H. Velasquez, W. Jy, J. J. Jimenez, E. Ahn, L. L. Horstman, A. O. Soriano, J. P. Zambrano, Y. S. Ahn, Elevation of endothelial microparticles, platelets, and leukocyte activation in patients with venous thromboembolism. J. Am. Coll. Cardiol. 45, 1467-1471 (2005).
124. S. Shrivastava, P. M. Ridker, R. J. Glynn, S. Z. Goldhaber, S. Moll, H. Bounameaux, K. A. Bauer, C. M. Kessler, M. Cushman, D-dimer, factor VIII coagulant activity, low-intensity warfarin and the risk of recurrent venous thromboembolism. J. Thromb. Haemost. 4, 1208-1214 (2006).
125. P. V. Jenkins, O. Rawley, O. P. Smith, J. S. O'Donnell, Elevated factor
126. Y. K. Park, N. S. Kim, S. K. Hann, S. Im, Identification of autoantibody to melanocytes and characterization of vitiligo antigen in vitiligo patients. J. Dermatol. Sci. 11, 111-120 (1996).
127. S. N. Wong, V. Shah, M. J. Dillon, Antineutrophil cytoplasmic antibodies in Wegener's granulomatosis. Arch. Dis. Child. 79, 246-250 (1998).