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The USC Adult Twin Cohorts: International Twin Study and California Twin Program

  • Wendy Cozen (a1) (a2) (a3), Amie E. Hwang (a1), Myles G. Cockburn (a1) (a2), Ann S. Hamilton (a1) (a2), John Zadnick (a1) and Thomas M. Mack (a1) (a2) (a3)
  • DOI:
  • Published online: 07 December 2012

The study of twin subjects permits the documentation of crude heritability and may promote the identification of specific causal alleles. We believe that at the current time, the chief research advantage of twins as subjects, especially monozygotic twins, is that the commonality of their genetic and cultural identity simplifies the interpretation of biological associations. In order to study genetic and environmental determinants of cancer and chronic diseases, we developed two twin registries, maintained at the University of Southern California: The International Twin Study (ITS) and the California Twin Program (CTP). The ITS is a volunteer registry of twins with cancer and chronic disease consisting of 17,245 twin pairs affected by cancer and chronic disease, respectively, ascertained by advertising in periodicals from 1980–1991. The CTP is a population-based registry of California-born twin pairs ascertained by linking the California birth records to the State Department of Motor Vehicles. Over 51,000 individual California twins representing 36,965 pairs completed and returned 16-page questionnaires. Cancer diagnoses in the California twins are updated by regular linkage to the California Cancer Registry. Over 5,000 cancer patients are represented in the CTP. Twins from both registries have participated extensively in studies of breast cancer, melanoma, lymphoma, multiple sclerosis, systemic lupus erythematosus, diabetes mellitus type 1, mammographic density, smoking, and other traits and conditions.

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Corresponding author
Address for correspondence: Wendy Cozen, USC Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, MC-9175, Los Angeles, CA 90089-9175, USA. E-mail:
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T. Best , D. Li , A. D. Skol , T. Kirchhoff , S. A. Jackson , Y. Yasui , . . . K. Onel (2011). Variants at 6q21 implicate PRDM1 in the etiology of therapy-induced second malignancies after Hodgkin lymphoma. Nature Medicine, 17, 941943.

J. D. Buckley , C. M. Buckley , N. E. Breslow , G. J. Draper , P. K. Roberson , & T. M. Mack (1996). Concordance for childhood cancer in twins. Medical and Pediatric Oncology, 26, 223229.

Y. Chen , F. Rao , J. L. Rodriguez-Flores , M. Mahata , M. M. Fung , M. Stridsberg , . . . D. T. O'Connor (2008). Naturally occurring human genetic variation in the 3’-untranslated region of the secretory protein chromogranin A is associated with autonomic blood pressure regulation and hypertension in a sex-dependent fashion. Journal of the American College of Cardiology, 52, 14681481.

M. G. Cockburn , W. Black , W. McKelvey , & T. M. Mack (2001a). Determinants of melanoma in a case-control study in twins. Cancer Causes and Control, 12, 615625.

M. Cockburn , A. Hamilton , W. Cozen , J. Zadnick , & T. Mack (2002). Chronic diseases in a large population-based cohort. Twin Research, 5, 460467.

M. G. Cockburn , A. S. Hamilton , & T. M. Mack (2001b). Recall bias in self-reported melanoma risk factors. American Journal of Epidemiology, 153, 10211026.

M. Cockburn , A. Hamilton , & T. Mack (2007). The simultaneous assessment of constitutional, behavioral, and environmental factors in the development of large nevi. Cancer Epidemiology, Biomarkers and Prevention, 16, 200206.

M. G. Cockburn , A. S. Hamilton , J. Zadnick , W. Cozen , & T. M. Mack (2001c). Development and representativeness of a large population-based cohort of native Californian twins. Twin Research, 4, 242250.

V. K. Cortessis , D. C. Thomas , A. J. Levine , C. V. Breton , T. M. Mack , K. D. Siegmund , . . . P. W. Laird (2012). Environmental epigenetics: Prospects for studying epigenetic mediation of exposure-response relationships. Human Genetics, 131, 1565–158.

W. Cozen , D. Diaz-Sanchez , J. W. Gauderman , J. Zadnick , M. G. Cockburn , P. S. Gill , . . . T. M. Mack (2004a). Th1 and Th2 cytokines and IgE levels in identical twins with varying levels of cigarette consumption. Journal of Clinical Immunology, 24, 617622.

W. Cozen , P. S. Gill , S. A. Ingles , R. Masood , O. Martinez-Maza , M. G. Cockburn , . . . T. M. Mack (2004b). IL-6 phenotype and genotype are associated with a risk of young adult Hodgkin's disease. Blood, 103, 32163221.

W. Cozen , P. S. Gill , M. T. R. Salam , A. Nieters , R. Masood , M. G. Cockburn , . . . T. M. Mack (2008). Interleukin-2, interleukin-12 and interferon-(gamma) levels and risk of young adult Hodgkin lymphoma. Blood, 111, 33773382.

W. Cozen , A. S. Hamilton , P. Zhou , M. T. Salam , D. M. Deapen , B. N. Nathwani , . . . T. M. Mack (2009). A protective role for early oral exposures in the etiology of young adult Hodgkin lymphoma. Blood, 114, 40144020.

W. Cozen , D. Li , T. Best , D. Van Den Berg , P.-A. Gourraud , V. K. Cortessis , . . . K. Onel (2012). A genome-wide meta-analysis of nodular sclerosing Hodgkin lymphoma identifies risk loci at 6p21.32. Blood, 119, 469475.

A. S. Hamilton , C. N. Lessov-Schlaggar , M. G. Cockburn , J. B. Unger , W. Cozen , & T. M. Mack (2006). Gender differences in determinants of smoking initiation and persistence in California twins. Cancer Epidemiology Biomarkers and Prevention, 15, 11891197.

A. S. Hamilton , & T. M. Mack (2003). Puberty and genetic susceptibility to breast cancer. New England Journal of Medicine, 348, 23132322.

International Multiple Sclerosis Genetics Consortium, Wellcome Trust Case Control Consortium 2, S. Sawcer , G. Hellenthal , M. Pirinen , C. C. Spencer , . . . A. Compston (2011). Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature, 476, 214219.

T. Islam , W. J. Gauderman , W. Cozen , A. S. Hamilton , M. E. Burnett , & T. M. Mack (2006). Differential twin concordance for multiple sclerosis by latitude: Genetic or environmental determinants? Annals of Neurology, 60, 5664.

D. Kumar , N. S. Gemayel , D. Deapen , D. Kapadia , P. H. Yamashita , M. Lee , . . . T. M. Mack (1993). North-American twins with IDDM genetic, etiological, and clinical significance of disease concordance according to age, zygosity, and the interval after diagnosis in first twin. Diabetes, 42, 13511363.

T. M. Mack , W. Cozen , D. K. Shibata , L. M. Weiss , B. N. Nathwani , A. M. Hernandez , . . . E. B. Rappaport (1995). Concordance in identical twins suggests genetic susceptibility to young adult Hodgkin's disease. New England Journal of Medicine, 332, 413418.

T. M. Mack , D. Deapen , & A. S. Hamilton (2000). Representativeness of a roster of North American twins with chronic disease. Twin Research, 3, 3340.

T. M. Mack , A. S. Hamilton , M. Press , A. Diep , & E. B. Rappaport (2002). Heritable breast cancer in twins. British Journal of Cancer, 87, 294300.

J. Peto , & T. M. Mack (2000). High constant incidence in twins and other relatives of women with breast cancer. Nature Genetics, 26, 411414.

G. Ursin , E. O. Lillie , E. Lee , M. G. Cockburn , N. J. Schork , W. Cozen , . . . T. M. Mack (2009). The relative importance of genetics and environment on mammographic density. Cancer Epidemiology Biomarkers and Prevention, 18, 102112.

L. Wang , F. Rao , K. Zhang , M. Mahata , J. L. Rodriguez-Flores , M. M. Fung , . . . D. T. O'Connor (2009). Neuropeptide Y(1) receptor NPY1R discovery of naturally occurring human genetic variants governing gene expression in cella as well as pleiotropic effects on autonomic activity and blood pressure in vivo. Journal of the American College of Cardiology, 54, 944954.

L. Zhang , F. Rao , J. Wessel , B. P. Kennedy , B. K. Rana , L. Taupenot , . . .D. T. O'Connor (2004). Functional allelic heterogeneity and pleiotropy of a repeat polymorphism in tyrosine hydroxylase: Prediction of catecholamines and response to stress in twins. Physiological Genomics, 19, 277291.

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Twin Research and Human Genetics
  • ISSN: 1832-4274
  • EISSN: 1839-2628
  • URL: /core/journals/twin-research-and-human-genetics
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