Christine E. McLaren
Vice Chair for Academic Affairs, Epidemiology
Scientific Member, Genetic Epidemiology Research Institute
Director of Biostatistics, Chao Family Comprehensive Cancer Center
|Finite Mixture Distributions, Goodness-of-fit Testing, Statistical Modeling of Biological Processes,Iron Deficiency Anemia, Iron Overload, Hemochromatosis, Epidemiology|
|URLs||Dept. of Epidemiology - School of Medicine|
|Genetic Epidemiology Research Institute (GERI)|
|Phi Theta Kappa Scholastic Honorary; Stanford University Prospective Teacher Fellowship; Case Western Reserve University Tuition Fellowship; American Statistical Association Presentation Award; American Heart Association Research Fellowship; Visiting Scientific Officer, Wales College of Medicine, U.K.; Fellow, Royal Statistical Society/Institute of Statistics; Senior Honorary Research Fellowship, University of Glasgow, Scotland, U.K.; Phi Kappa Phi Honor Society; Fellow, American Statistical Association; Raybould Visiting Fellowship, University of Queensland, Australia; Senior International Fellowship awarded by the NIH Fogarty International Center; Minnesota College Science Teacher of the Year, Minnesota Academy of Science; Moorhead State University Award for Excellence in Research; University Deans’ Council Nominee for the “1997 U.S. Professors of the Year Program”, Carnegie Foundation for the Advancement of Teaching; American Statistical Association Service Award.|
Statistical models provide insight into the structure of data. Models of biological processes can assist with distinguishing between health and disease. Dr. McLaren's statistical modeling research has concentrated on mixture distribution analysis, goodness-of-fit testing, and hierarchical regression modeling Theof longitudinal data. Medical applications including disease prevalence and estimation of iron overload and hemochromatosis, analysis of distributions of red blood cell volume and hemoglobin concentration in iron deficiency anemia, detection of cisplatin-induced anemia in patients undergoing cancer chemotherapy, and screening for hepatocelluar carcinoma. As a result of her experience with statistical modeling and collaborative medical research, in January of 2000, Dr. McLaren received a $4 million 5-year contract awarded by NIH/NHLBI, "Screening for Iron Overload and Hereditary Hemochromatosis: Field Center". With her oversight, 20,400 primary care patients enrolled in the study at the University of California, Irvine.
Current and Recent Research Projects
IRON OVERLOAD AND HEMOCHROMATOSIS
Prevalence Estimation: There is now incontrovertible evidence that early diagnosis and therapy of hereditary hemochromatosis prevents virtually all manifestations of the disease and results in normal life expectancy. In contrast, unrecognized and untreated disease leads to cirrhosis, hepatocellular carcinoma and other lethal complications. We analyzed the distribution of transferrin saturation values in the second National Health and Nutrition Examination Survey to estimate the prevalence of hemochromatosis homozygotes and heterozygotes in the United States population. The gene frequencies for hemochromatosis were estimated to be 0.081 for males and 0.070 for females corresponding to prevalences of homozygotes of 6.6 and 4.8 per thousand. Our results confirm that the gene for hemochromatosis is common in the white population of the United States.
Disease Screening: Cost-effectiveness analyses indicate that the cost of screening and treatment for hemochromatosis is far less than the medical cost of treating chronic disabilities resulting from the secondary disease conditions such as cirrhosis and diabetes due to iron overload. In population screening, the number and proportion of individuals identified as having hemochromatosis will depend, in part, upon the specific initial screening criteria applied. Our research efforts have concentrated on identifying appropriate screening values for transferrin saturation to identify hemochromatosis heterozygotes and homozytoges.
MIXTURE DISTRIBUTION ANALYSIS
Maximum likelihood estimation of finite mixture models using the EM algorithm: Another primary research interest has been in finite mixture distributions and their applications in medicine. After examining the theoretical basis for the statistical evaluation of red blood cell volume distributions we developed a mathematical model of the distribution of the volumes of circulating red cells and verified predictions in healthy individuals and patients with anemia. Analysis of the empirical data required development of a method for log normal parameter estimation appropriate to grouped truncated distributions. We then developed statistical methods for detection of mixtures of two log normal distri-butions in doubly-truncated data when the sample size is large. Alterations in erythrocyte subpopulations were quantified in untransfused patients with refractory anemia, sideroblastic anemia, and patients treated for iron deficiency anemia.
Hierarchical models for screening of iron deficiency anemia: In this joint work with Dr. Padhraic Smyth, UCI Department of Information and Computer Science, we developed a model of the bivariate distribution of hemoglobin concentration and red blood cell volume. A new mixture fitting algorithm was devised to analyze data measured using an automated blood cell analyzer. A two-level classification technique of model parameters achieved accurate discrimination between healthy individuals and patients with disorders of anemia.
SEQUENTIAL ANALYSIS OF LABORATORY DATA
Patient-specific Sequential Analysis of Laboratory Data: For this area of concentration, our research group developed statistical methods to sequentially analyze laboratory test results and identify departures from past values. These methods include hierarchical multiple regression modeling, with a weighted minimum risk criteria for model selection, to choose models indicating changes in mean values over time. Clinical applications have included detection of developing iron deficiency anemia, identification of anemia due to cisplatin-based chemotherapy, regulation of T cells numbers in Gaucher disease, and screening for hepatocelluar carcinoma. These methods promise to provide more sensitive techniques for improved diagnostic evaluation of diseases and serial monitoring of response to therapy.
|Publications||McLaren CE, Garner CP, Constantine CC, McLachlan S, Vulpe CD, Snively BM, Gordeuk VR, Nickerson DA, Cook JD, Leiendecker-Foster C, Beckman KB, Eckfeldt JH, Barcellos LF, Murray JA, Adams PC, Acton RT, Killeen AA, McLaren GD. Genome-wide association study identifies genetic loci associated with iron deficiency. PLoS One 6(3):e17390, 2011.|
|Garcia AM, McLaren CE, Meyskens FL, Jr. Melanoma: is hair the root of the problem? Pigment Cell Melanoma Res 24(1):110-118, 2011.|
Osborne NJ, Gurrin LC, Allen KJ, Constantine CC, Delatycki MB, McLaren CE, Gertig DM, Anderson GJ, Southey MC, Olynyk JK, Powell LW, Hopper JL, Giles GG, English DR. HFE C282Y homozygotes are at increased risk of breast and colorectal cancer. Hepatology 51(4):1311-1318, 2010.
Meyskens FL, Jr., McLaren CE. Chemoprevention, risk reduction, therapeutic prevention, or preventive therapy? J Natl Cancer Inst 102(24):1815-1817, 2010.
McLaren CE, Barton JC, Eckfeldt JH, McLaren GD, Acton RT, Adams PC, Henkin LF, Gordeuk VR, Vulpe CD, Harris EL, Harrison BW, Reiss JA, Snively BM. Heritability of serum iron measures in the hemochromatosis and iron overload screening (HEIRS) family study. Am J Hematol 85(2):101-105, 2010.
|Zell JA, McLaren CE, Chen WP, Thompson PA, Gerner EW, Meyskens FL. Ornithine decarboxylase-1 polymorphism, chemoprevention with eflornithine and sulindac, and outcomes among colorectal adenoma patients. J Natl Cancer Inst 102(19):1513-1516, 2010.|
|Constantine CC, Anderson GJ, Vulpe CD, McLaren CE, Bahlo M, Yeap HL, Gertig DM, Osborne NJ, Bertalli NA, Beckman KB, Chen V, Matak P, McKie AT, Delatycki MB, Olynyk JK, English DR, Southey MC, Giles GG, Hopper JL, Allen KJ, Gurrin LC. A novel association between a SNP in CYBRD1 and serum ferritin levels in a cohort study of HFE hereditary haemochromatosis. Br J Haematol 147(1):140-149, 2009.|
|McLaren CE, Chen WP, Nie K, Su MY. Prediction of malignant breast lesions from MRI features: a comparison of artificial neural network and logistic regression techniques. Acad Radiol 16(7):842-851, 2009.|
|Zell JA, Pelot D, Chen WP, McLaren CE, Gerner EW, Meyskens FL. Risk of cardiovascular events in a randomized placebo-controlled, double-blind trial of difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas. Cancer Prev Res (Phila) 2(3):209-212, 2009.|
|McLaren CE, Gordeuk VR, Chen WP, Barton JC, Acton RT, Speechley M, Castro O, Adams PC, Snively BM, Harris EL, Reboussin DM, McLachlan GJ, Bean R. Bivariate mixture modeling of transferrin saturation and serum ferritin concentration in Asians, African Americans, Hispanics, and Whites in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. Translational Research 151(2):97-109, 2008.|
|McLaren CE, Fujikawa-Brooks S, Chen WP, Gillen DL, Gerner E., Meyskens FL. Longitudinal assessment of air conduction audiograms in a phase III clinical trial of DFMO and sulindac for prevention of sporadic colorectal adenomas. Cancer Prevention Research 1:514-521, 2008.|
|Meyskens FLM, McLaren CE, Pelot D, Fujikawa-Brooks S, Carpenter PM, Hawk E, Kelloff G., Lawson MJ, Kidao J, McCracken J, Albers C, Ahnen DJ, Turgeon DK, Goldschmidt S, Lance P, Hagedorn CH, Gillen DL, Gerner E. Difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas: a randomized placebo-controlled double-blind trial. Cancer Prevention Research 1:32-38, 2008.|
|Allen KJ, Gurrin LC, Constantine CC, Osborne NJ, Delatycki MB, Nicoll AJ, McLaren CE, Bahlo M, Nisselle AE, Vulpe CD, Anderson GJ, Giles GG, English DR. Hopper JL, Olynyk JK, Powell LW, Gertig DM. A prospective study of mutations in the HFE gene and development of hereditary hemochromtosis disease. New England Journal of Medicine 358(3):221-230, 2008.|
|Constantine CC, Gurrin LC, McLaren CE, Bahlo M, Anderson GJ, Vulpe CD, Forrest S, Allen KJ, Gertig DM. SNP selection for genes of iron metabolism: a study of genetic modifiers of hemochromatosis. BMC Medical Genetics 9:18, 2008.|
|McLaren CE, Barton JC, Gordeuk VR, Wu L, Adams PC, Reboussin DM, Speechley M, Chang H, Acton RT, Harris EL, Castro O, for the Hemochromatosis and Iron Overload Screening Study Research Investigators. Determinants and Characteristics of Mean Corpuscular Volume and Hemoglobin Concentration in White HFE C282Y Homozygotes in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. American Journal of Hematology 82:808-905, 2007.|
|McLaren CE, Li K-T, McLaren GD, Gordeuk VR, Snively BG, Reboussin DM, Barton JC, Acton RT, Dawkins FW, Harris EL, Moses GC, and Adams PC. Mixture models of serum biochemical measures in screening for hemochromatosis and iron overload. Translational Research 148:196-206, 2006.|
|Adams PC, Reboussin DM, Barton JC, McLaren CE, Eckfeldt JH, McLaren GD, Dawkins FW, Acton RT, Harris EL, Gordeuk VR, Leiendecker-Foster C, Speechley M, Snively BM, Holup JL, Thomson E, Sholinsky P. Hemochromatosis and Iron Overload Screening (HEIRS) Study: Screening of a primary care population. New England Journal of Medicine 352:1769-1778, 2005.|
|Carpenter PM, Linden K, McLaren CE, Li K-T, Arain S, Barr RJ, Meyskens FL. Nuclear morphometry of actinic keratosis and sun-damaged skin. Cancer Epidemiology, Biomarkers, and Prevention 13:1996-2002, 2004.|
|McLaren CE, Li K-T, Garner CP, Beutler E, Gordeuk, VR. Mixture Distribution analysis of phenotypic markers reflecting HFE gene mutations. Blood 102:4563-4566, 2003.|
|McLaren CE, Barton JC, Adams PC, Harris EL, Acton RT, Press N, Reboussin DM, McLaren GD, Sholinsky P, Walker AP, Gordeuk VR, Leiendecker-Foster C, Dawkins FW, Eckfeldt JH, Mellen BG, Speechley M, Thomson E for the Hemochromatosis and Iron Overload Study Research Investigators. Hemochromatosis and iron overload screening (HEIRS) Study Design for an Evaluation of 100,000 primary care-based adults. The American Journal of the Medical Sciences 325:53-62, 2003.|
|Cadez IV, Smyth P, McLachlan GJ, McLaren CE. Maximum likelihood estimation of mixture densities for binned and truncated multivariate data. Machine Learning 47:7-34, 2002.|
|McLaren CE, Li K-T, Gordeuk VR, Hasselblad V, McLaren GD, Looker AC. Relationship between transferrin saturation and iron stores in U.S. African-American and Caucasian Populations. Blood 98-2345-51, 2001.|
|McLaren CE. Ascertainment of hemochromatosis Heterozygosity. In Hemochromatosis: Genetics, Pathophysiology, Diagnosis, and Treatment. In: Eds, Barton JC, Edwards CQ, eds. Cambridge, England: Cambridge University Press; 2000:419-426.|
|McLaren CE, Kambour EL, McLachlan GJ, Lukaski HC, Li X, Brittenham GM,McLaren GD. Patient-specific analysis of sequential haematological data by multiple linear regression and mixture distribution modelling. Statistics in Medicine 19:83-98, 2000.|
|Olivieri NF, Brittenham GM, McLaren CE, Templeton DM, Cameron RG, McClelland RA, Burt AD, Fleming KA. Long-term safety and effectiveness of iron-chelation therapy with deferiprone for thalassemia major. New England Journal of Medicine 339:417-23, 1999.|
|McLaren CE, McLachlan GJ, Halliday JW, Webb SI, Leggett BA, Jazwinska EC, Crawford DH, Gordeuk VR, McLaren GD, Powell LW. Distribution of transferrin saturation in an Australian population: relevance to the early diagnosis of hemochromatosis. Gastroenterology 114:543-9, 1998.|
|McLaren C, Bull B, Kambour E, Westengard J, Caswell M, Emery P, Stuart J. A Statistical approach to the selection of better laboratory tests. Laboratory Hematology 3:97-102, 1997.|
|McLaren CE. Mixture models in haematology: a series of case studies. Statistical Methods in Medical Research 5:129-53, 1996.|
|McLaren CE, Gordeuk VR, Looker AC, Hasselblad V, Edwards CQ, Griffen LM, Kushner JP, Brittenham GM. Prevalence of heterozygotes for hemochromatosis in the white population of the United States. Blood 86:2021-7, 1995.|
|McLachlan J, McLaren CE, Matthews D. An Algorithm for the Likelihood Ratio Test of One versus two components in a normal mixture model fitted to grouped and truncated data. Communications in Statistics: Simulation and Computation 24(4):965-985, 1995.|
|McLaren CE, Legler JM, Brittenham GM. The generalized chi-square goodness-of-fit test. J Royal Stat Soc (Series D), The Statistician 43 (2):247-258, 1994.|
|McLaren CE. Houwen B, Koepke JA, Rowan RM, McKay PJ, Ortner BR, Bishop ML. Analysis of red blood cell volume distributions using the ICSH reference method: detection of sequential changes in distributions determined by hydrodynamic focusing. Clin Lab Haematol 15(3):173-184, 1993.|
|Gordeuk VR, Thuma PE, Brittenham GM, McLaren CE, Parry D, Backenstose AR, Msiska R, Holmes L, McKainley E, Vargas L, Biemba G., Olness K, Aikawa M. Effect of iron chelation therapy on recovery from deep coma in children with cerebral malaria. New Engl J Med 327(21):1473-1477, 1992.|
|McLaren CE, Wagstaff M, Brittenham GM, Jacobs A. Detection of two component mixtures of lognormal distributions in grouped doubly-truncated data. Biometrics 47(3):607-622, 1991.|
|McLaren CE, Brittenham GM, Hasselblad V. Statistical and graphical evaluation of erythrocyte volume distributions. Am J Physiol 252 (Heart Circ Physiol 21):H857-H866, 1987|
|McLaren CE, Brittenham GM, Hasselblad V. Analysis of the volume of red blood cells: application of the expectation-maximization algorithm to grouped data from the doubly-truncated lognormal distribution. Biometrics 42(1):143-158, 1986.|
|McLaren CE, Brittenham GM, Gordeuk VR, Hughes MA, Keating LJ. Statistical modelling of the distribution of red blood cell volumes in iron deficiency anemia using the expectation-maximization algorithm. Statistician 35(2):135-142, 1986.|
|Grants||NCI Subcontract 79745CBS36, "Cancer Biomedical Informatics Grid: C3D Module Adopter", (C.E. McLaren, P.I.)|
|NIH/NHLBI/NHGRI, Contract N01-HC-05190,“Screening for Iron Overload and Hereditary Hemochromatosis—Field Center”, (C.E. McLaren, P.I.)|
|Department of Veterans Affairs Grant 121F, “Prevalence of Iron Overload and Frequency of the Hemochromatosis Gene”, (G.D. McLaren, P.I.; C.E. McLaren, Co-P.I.).|
|National Center for Health Statistics OMB No. 0990-0115, “Statistical Modeling of the Joint Distribution of Serum Transferrin Saturation and Serum Ferritin Data from NHANES III to Predict the Probability of Hemochromatosis Heterozygosity and Homozygosity for Hemochromatosis in U.S. White Adults”, (C. E. McLaren, P.I.)|
|Centre Technique de Cooperation Agricole et Rurale (CTA), “IBC98 Special Sessions for Developing Country Biometricians”, (C. E. McLaren, P.I.)|
|NIH, P30 CA-62203, “UCI Cancer Center Support Grant”, (F. L. Meyskens, Jr., P.I.; C. E. McLaren, Director of Biostatistics Shared Resource)|
|NIH, Academic Enhancement Research Award, R15 HL 58203. “Statistical Basis for Hemochromatosis Screening”, (C.E. McLaren, P.I.)|
|Sysmex Corporation,Cooperative R&D Agreement, “Trend Analysis for Reticulocyte Maturation and Quality Control”, (C. E. McLaren, P.I.)|
|The American-Portuguese Biomedical Research Fund, “Longitudinal Population Studies of Families with Hemochromatosis", (C. E. McLaren, P.I.)|
|NIH, Fogarty International Center, “Generalized Chi-squared Test for Comparing Distributions”, (C. E. McLaren, P.I.)|
|Minnesota Higher Education Board, Eisenhower Mathematics and Science Education Act grant, “Project IMPACT: Integrated Math and Physical Science”, (C. E. McLaren, P.I.)|
|NIH, Academic Research Enhancement Award, R15 HL48349, “Sequential Analysis of Hematologic Measurements”. (C. E. McLaren, P.I)|
|NIH, Academic Research Enhancement Award, R15 HL42681, “Mixtures of Red Blood Cell Volume Distributions”, (C. E. McLaren, P.I.)|
|Wellcome Research Travel Grant, “Microcomputer Analysis of Cell Volume Distributions”, (C. E. McLaren, P.I.)|
|Greater Minnesota Corporation, Technology Research Grant, TG-3000, “Automated Hematology Data Analysis System”, (C. E. McLaren, P.I.)|
|National Science Foundation: Instructional Laboratory Improvement Grant, USE-8851944, “Instructional Computer Laboratory for Introduction to Statistics”. (C. E. McLaren, P.I.)|
|University of Wales College of Medicine, Blood Research Fund Grant, “Red Blood Cell Volume Distributions in Sideroblastic Anemia”. (C. E. McLaren, P.I.)|
|American Heart Association: Research Fellowship, “Analysis of Red Cell Volume Distributions in Anemia”, (C.E. McLaren, P.I.)|
American Statistical Association (FELLOW, 1993), Chair, Council of Chapters Governing Board, 2004; Executive Committee, Biometrics Section, 2001-2004; Chair, Section on Statistical Education, 1999; River Valley Chapter, Chapter Representative, 1992-95, President, 1990-91, Secretary, 1989-90.
International Biometrics Society, Executive Council, 2003-2006; President-Elect, Western North American Region (WNAR), 2004; Regional Advisory Board, WNAR, 2001-2003; IBS Education Committee, 1996-1999.
Council on Undergraduate Research. Mathematical and Computer Sciences Council, Councilor, 1992-2000.
International BioIron Society
Royal Statistical Society (FELLOW, 1990)
|Research Center||Genetic Epidemiology Research Institute|
|Link to this profile||http://www.faculty.uci.edu/profile.cfm?faculty_id=4517|