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Training Grant-
Biology of Aging
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Corinne Engelman

Corinne D. Engelman

Ph.D. University of Colorado Health Sciences Center
Associate Professor, Department of Population Health Sciences
cengelman@wisc.edu
http://pophealth.wisc.edu/corinne-engelman


Genetic Epidemiology of Alzheimer's Disease and Vitamin D Deficiency

The genetic makeup of individuals plays an important role in health and disease. However, the influence of genes is extremely complex, typically involving multiple genetic variants interacting with each other and with environmental (i.e., non-genetic) factors. As a genetic epidemiologist, Dr. Engelman's research program is focused on determining the impact of these gene-gene and gene-environment interactions on serum vitamin D concentration and cognitive function and decline related to Alzheimer's disease.

Vitamin D is associated with many health outcomes, including skeletal health, cancer, immune responses, type 2 diabetes and metabolic syndrome, cardiovascular diseases and hypertension, neuropsychological functioning, and all-cause mortality. Dr. Engelman is examining genetic and environmental factors influencing vitamin D concentrations in the blood, and the effect of interactions between these factors. Dr. Engelman's findings indicate the important role that gene-environment interactions will play in personalized medicine, where an individual's response to dietary supplements, drugs, and other therapies depends on genetic factors.

Alzheimer's disease (AD) is a genetically complex disease. Although the genetic causes of autosomal dominant, early-onset AD are well established, those of the late-onset, non-Mendelian form of AD remain elusive. In fact, the heritability estimates of non-Mendelian AD range from 60-80%, but about half of the genetic risk remains unexplained. Several genome-wide association studies (GWAS) of late-onset AD have recently been reported with many new and interesting single nucleotide polymorphisms (SNPs) showing a significant association. However, the discovery of genetic variants through GWAS represents just a first step in the challenging process of piecing together the complex biological picture of late-onset AD. Next steps include determining the genetic association with AD-related endophenotypes, which can offer substantial insight into the pathophysiology of disease and examining potential interactions between SNPs and with environmental factors. Dr. Engelman is studying these in the Wisconsin Registry for Alzheimer's Prevention (WRAP), a longitudinal study of middle-aged adults enriched for a parental history of AD.



Representative Publications
Clark, L. R., Berman, S. E., Rivera-Rivera, L. A., Hoscheidt, S. M., Darst, B. F., Engelman, C. D., ... Asthana, S., Turski, P., Wieben, O., & Johnson, S. C. (2017). Macrovascular and microvascular cerebral blood flow in adults at risk for Alzheimer's disease. Alzheimer's & Dementia, 7, 48-55.
View publication via DOI: DOI:10.1016/j.dadm.2017.01.002

Darst, B. F., Koscik, R. L., Racine, A. M., Oh, J. M., Krause, R. A., Carlsson, C. M., ... Bendlin, B. B., Okonkwo, O. C., ... Sager, M. A., Asthana, S., Johnson, S. C., & Engelman, C. D. (2017). Pathway-specific polygenic risk scores as predictors of amyloid-beta deposition and cognitive function in a sample at increased risk for Alzheimer's disease. Journal of Alzheimer's Disease, 55(2), 473-484.
View publication via DOI: DOI:10.3233/jad-160195

Clark, L. R., Racine, A. M., Koscik, R. L., Okonkwo, O. C., Engelman, C. D., Carlsson, C. M., Asthana, S., Bendlin, B. B., ... Sager, M. A., Christian, B. T., & Johnson, S. C. (2016). Beta-amyloid and cognitive decline in late middle age: Findings from the Wisconsin registry for Alzheimer's prevention study. Alzheimer's & Dementia, 12(7), 805-814.
View publication via DOI: DOI:10.1016/j.jalz.2015.12.009

Clark, L. R., Koscik, R. L., Nicholas, C. R., Okonkwo, O. C., Engelman, C. D., Bratzke, L. C., ... Bendlin, B. B., Carlsson, C. M., Asthana, S., Sager, M. A., ... Johnson, S. C. (2016). Mild cognitive impairment in late middle age in the Wisconsin registry for Alzheimer's prevention study: Prevalence and characteristics using robust and standard neuropsychological normative data. Archives of Clinical Neuropsychology. Advance online publication.
View publication via DOI: DOI:10.1093/arclin/acw024

Darst, B. F., & Engelman, C. D. (2016). Transmission and decorrelation methods for detecting rare variants using sequencing data from related individuals. BMC Proceedings, 10(Suppl 7), 203-207.
View publication via DOI: DOI:10.1186/s12919-016-0031-z

Engelman, C. D., Greenwood, C. M., Bailey, J. N., Cantor, R. M., Kent, J. W., Jr., Konig, I. R., ... Almasy, L. (2016). Genetic analysis workshop 19: Methods and strategies for analyzing human sequence and gene expression data in extended families and unrelated individuals. BMC Proceedings, 10(Suppl 7), 67-70.
View publication via DOI: DOI:10.1186/s12919-016-0007-z

Sippy, R., Kolesar, J. M., Darst, B. F., & Engelman, C. D. (2016). Prioritization of family member sequencing for the detection of rare variants. BMC Proceedings, 10(Suppl 7), 227-231.
View publication via DOI: DOI:10.1186/s12919-016-0035-8

Darst, B. F., Koscik, R. L., Hermann, B. P., La Rue, A., Sager, M. A., Johnson, S. C., & Engelman, C. D. (2015). Heritability of cognitive traits among siblings with a parental history of Alzheimer's disease. Journal of Alzheimer's Disease, 45(4), 1149-1155.
View publication via DOI: DOI:10.3233/jad-142658

Millen, A. E., Meyers, K. J., Liu, Z., Engelman, C. D., Wallace, R. B., LeBlanc, E. S., Tinker, L. F., Iyengar, S. K., Robinson, J. G., Sarto, G. E., & Mares, J. A. (2015). Association between vitamin D status and age-related macular degeneration by genetic risk. JAMA Ophthalmology, 133(10), 1171-1179.
View publication via DOI: DOI:10.1001/jamaophthalmol.2015.2715

Givens, M. L., Malecki, K. C., Peppard, P. E., Palta, M., Said, A., Engelman, C. D., Walsh, M. C., & Nieto, F. J. (2015). Shiftwork, sleep habits, and metabolic disparities: Results from the survey of the health of Wisconsin. Sleep Health, 1(2), 115-120.
View publication via DOI: DOI:10.1016/j.sleh.2015.04.014

Meyers, K. J., Mares, J. A., Igo, R. P., Jr., Truitt, B., Liu, Z., Millen, A. E., . . . Engelman, C. D., . . . Iyengar, S. K. (2014). Genetic evidence for role of carotenoids in age-related macular degeneration in the Carotenoids in Age-Related Eye Disease Study (CAREDS). Investigative Ophthalmology and Visual Science, 55(1), 587-99.
View publication via DOI: DOI:10.1167/iovs.13-13216

Bailey, E. J., Malecki, K. C., Engelman, C. D., Walsh, M. C., Bersch, A. J., Martinez-Donate, A. P., . . . Nieto, F. J. (2014). Predictors of discordance between perceived and objective neighborhood data. Annals of Epidemiology, 24(3),214-21.
View publication via DOI: DOI:10.1016/j.annepidem.2013.12.007

Engelman, C. D. (2014). Towards personalized prevention of obesity: Can vitamin D negate the FTO effect? Diabetes, 63(2), 405-406.
View publication via DOI: DOI:10.2337/db13-1714

Engelman, C. D., Koscik, R. L., Jonaitis, E. M., Hermann, B. P., La Rue, A., & Sager, M. A. (2014). Investigation of triggering receptor expressed on myeloid cells 2 variant in the Wisconsin registry for Alzheimer's prevention. Neurobiology of Aging, 35(6), 1252-1254.
View publication via DOI: DOI:10.1016/j.neurobiolaging.2013.11.013

Yao, C., Leng, N., Weigel, K.A., Lee, K.E., Engelman, C.D., & Meyers, K.J. (2014). Prediction of Genetic Contributions to Complex Traits using Whole Genome Sequencing Data. BMC Proceedings, 8(Suppl 1), S68.

Sung, Y. J., Korthauer, K. D., Swartz, M. D., & Engelman, C. D. (2014). Methods for collapsing multiple rare variants in whole genome sequence data. Genetic Epidemiology, 38 (Suppl 1), S13-20.
View publication via DOI: DOI:10.1002/gepi.21820

Engelman, C. D., Bo, R., Zuelsdorff, M., Steltenpohl, H., Kirby, T., & Nieto, F. J. (2014). Epidemiologic study of the C-3 epimer of 25-hydroxyvitamin D3 in a population-based sample Clinical Nutrition, 33(3):421-5.
View publication via DOI: DOI:10.1016/j.clnu.2013.06.005

Warren Andersen S, Trentham-Dietz, A., Gangnon, R.E., Hampton, J.M., Figueroa, J., Skinner, H.G., Engelman, C., Klein, B.E.K., Titus, L.J., Egan, K., & Newcomb, P.A. (2014). Reproductive windows, genetic loci and breast cancer risk. Annals of Epidemiology, 24(5), 376-382.
View publication via DOI: DOI:10.1016/j.annepidem.2014.02.007

Warren, Andersen, S., Trentham-Dietz, A., Gangnon, R.E., Hampton, J.M., Skinner, H.G., Engelman, C.D., Klein, B.E., Titus, L.J., Egan, K.M., & Newcomb, P.A. (2014). Breast cancer susceptibility loci in association with age at menarche, age at natural menopause and the reproductive lifespan. Cancer Epidemiology 38(1), 62-5.
View publication via DOI: DOI:10.1016/j.canep.2013.12.001

Hale, L., Hill, T. D., Friedman, E., Javier Nieto, F., Galvao, L. W., Engelman, C. D., . . . Peppard, P. E. (2013). Perceived neighborhood quality, sleep quality, and health status: Evidence from the survey of the health of Wisconsin. Social Science and Medicine, 79, 16-22.
View publication via DOI: DOI:10.1016/j.socscimed.2012.07.021

Meyers, K. J., Johnson, E. J., Bernstein, P. S., Iyengar, S. K., Engelman, C. D., Karki, C. K., . . . Mares, J. A. (2013). Genetic determinants of macular pigments in women of the carotenoids in age-related eye disease study. Investigative Ophthalmology and Visual Science, 54(3), 2333-2345.
View publication via DOI: DOI:10.1167/iovs.12-10867

Engelman, C. D., Meyers, K. J., Iyengar, S. K., Liu, Z., Karki, C. K., Igo, R. P., Jr., . . . Mares, J. A., Millen, A. E. (2013). Vitamin D intake and season modify the effects of the GC and CYP2R1 genes on 25-hydroxyvitamin D concentrations. Journal of Nutrition, 143(1), 17-26.
View publication via DOI: DOI:10.3945/jn.112.169482

Zuelsdorff, M. L., Engelman, C. D., Friedman, E. M., Koscik, R. L., Jonaitis, E. M., Rue, A. L., & Sager, M. A. (2013). Stressful events, social support, and cognitive function in middle-aged adults with a family history of Alzheimer's disease. Journal of Aging and Health, 25(6), 944-959.
View publication via DOI: DOI:10.1177/0898264313498416

Engelman, C. D., Koscik, R. L., Jonaitis, E. M., Okonkwo, O. C., Hermann, B. P., La Rue, A., & Sager, M. A. (2013). Interaction between two cholesterol metabolism genes influences memory: Findings from the Wisconsin registry for Alzheimer's prevention. Journal of Alzheimers Disease, 36(4), 749-757.
View publication via DOI: DOI:10.3233/jad-130482

Bueno Filho, J. S., Morota, G., Tran, Q., Maenner, M. J., Vera-Cala, L. M., Engelman, C. D., & Meyers, K. J. (2011). Analysis of human mini-exome sequencing data from genetic analysis workshop 17 using a bayesian hierarchical mixture model. BMC Proceedings, 5(Suppl 9), S93.
View publication via DOI: DOI:10.1186/1753-6561-5-s9-s93

Ghosh, S., Bickeboller, H., Bailey, J., Bailey-Wilson, J. E., Cantor, R., Culverhouse, R., Daw, W., DeStefano, A. L., Engelman, C. D., . . . Almasy, L. (2011). Identifying rare variants from exome scans: The gaw17 experience. BMC Proceedings, 5 Suppl 9, S1.
View publication via DOI: DOI:10.1186/1753-6561-5-s9-s1

Engelman, C. D. (2011). Vitamin D recommendations: The saga continues. Journal of Clinical Endocrinology and Metabolism, 96(10), 3065-3066.
View publication via DOI: DOI:doi:10.1210/jc.2011-2355

Kluczynski, M. A., Lamonte, M. J., Mares, J. A., Wactawski-Wende, J., Smith, A. W., Engelman, C. D., . . . Millen, A. E. (2011). Duration of physical activity and serum 25-hydroxyvitamin D status of postmenopausal women. Annals of Epidemiology, 21(6), 440-449.
View publication via DOI: DOI:10.1016/j.annepidem.2010.11.011

Ye, K. Q., & Engelman, C. D. (2011). Detecting multiple causal rare variants in exome sequence data. Genetic Epidemiology, 35, S18-S21.
View publication via DOI: DOI:10.1002/gepi.20644

Bendlin, B.B., Carlsson, C.M., Gleason, C.E., Johnson, S.C., Sodhi, A., Gallagher, C.L., Puglielli, L., Engelman, C.D., Ries, M.L., Xu, G., Wharton, W., & Asthana, S. (2010). Midlife predictors of Alzheimer's disease. Maturitas, 65(2), 131-137.
View publication via DOI: DOI:10.1016/j.maturitas.2009.12.014

Engelman, C. D., Meyers, K. J., Ziegler, J. T., Taylor, K. D., Palmer, N. D., Haffner, S. M., . . . Norris, J. M. (2010). Genome-wide association study of vitamin D concentrations in Hispanic Americans: The iras family Study. Journal of Steroid Biochemistry and Molecular Biology, 122(4), 186-192.
View publication via DOI: DOI:10.1016/j.jsbmb.2010.06.013

Nieto, F. J., Peppard, P. E., Engelman, C. D., McElroy, J. A., Galvao, L. W., Friedman, E. M., . . . Malecki, K. C. (2010). The survey of the health of Wisconsin (show), a novel infrastructure for population health research: Rationale and methods. BMC Public Health, 10, 785.
View publication via DOI: DOI:10.1186/1471-2458-10-785

Schmitz, K.J., Skinner, H.G., Bautista, L.E., Fingerlin, T.E., Langefeld, C.D., Hicks, P.J., Haffner, S.M., Bryer-Ash, M., Wagenknecht, L.E., Bowden, D.W., Norris, J.M., & Engelman, C.D. (2009). Association of 25-hydroxyvitamin D with blood pressure in predominately 25-hydroxyvitamin D deficient Hispanic and African Americans. American Journal of Hypertension, 22(8), 867-870.
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View publication via DOI: DOI:10.1038/ajh.2009.88

Maenner, M.J., Denlinger, L.C., Langton, A., Meyers, K.J., Engelman, C.D., & Skinner, H.G. (2009). Detecting gene-by-smoking interactions in a genome-wide association study of early-onset coronary heart disease using random forests. BMC Proceedings, 3(Suppl 7), S88.
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View publication via DOI: DOI:10.1002/gepi.20475

Yao, L., Zhong, W., Zhang, Z., Maenner, M.J., & Engelman, C.D. (2009). Classification tree for detection of single-nucleotide polymorphism (SNP)-by-SNP interactions related to heart disease: Framingham Heart Study. BMC Proceedings, 15, 3.

Gonzalez-Recio, O., de Maturana, E.L., Vega, A.T., Engelman, C.D., & Broman, K.W. (2009). Detecting single-nucleotide polymorphism by single-nucleotide polymorphism interactions in rheumatoid arthritis using a two-step approach with machine learning and a Bayesian threshold least absolute shrinkage and selection operator (LASSO) model. BMC Proceedings, 15, 3.

Shim, H., Chun, H., Engelman, C.D., & Payseur, B.A. (2009). Genome-wide association studies using single-nucleotide polymorphisms versus haplotypes: An empirical comparison with data from the North American Rheumatoid Arthritis Consortium. BMC Proceedings, 15, 3.
View publication via DOI: DOI:10.1186/1753-6561-3-s7-s35

Young, K.A., Engelman, C.D., Langefeld, C.D., Hairston, K.G., Haffner, S.M., Bryer-Ash, M., & Norris, J.M. (2009). Association of plasma vitamin D levels with adiposity in Hispanic and African Americans. Journal of Clinical Endocrinology & Metabolism, 94(9), 3306-3313.
View publication via DOI: DOI:10.1210/jc.2009-0079

Engelman, C. D., Baurley, J. W., Chiu, Y.-F., Joubert, B. R., Lewinger, J. P., Maenner, M. J., . . . Gauderman, W. J. (2009). Detecting gene-environment interactions in genome-wide association data. Genetic Epidemiology, 33(S1), S68-S73.
View publication via DOI: DOI:10.1002/gepi.20475

An, P., Mukherjee, O., Chanda, P., Yao, L., Engelman, C. D., Huang, C.-H., . . . Province, M. A. (2009). The challenge of detecting epistasis (gxg interactions): Genetic analysis workshop 16. Genetic Epidemiology, 33(S1), S58-S67.
View publication via DOI: DOI:10.1002/gepi.20474

Engelman, C.D., Fingerlin, T.E., Langefeld, C.D., Hicks, P.J., Rich, S.S., Wagenknecht, L.E., Bowden, D.W., & Norris, J.M. (2008). Genetic and environmental determinants of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels in hispanic and african americans. J. Clin. Endocrinol. Metab., 93(9), 3381-8.
View publication via DOI: DOI:10.1210/jc.2007-2702

James, K., Weitzel, L., Engelman, C.D., Zerbe, G., & Norris, J.M. (2003). The use of linear mixed models for phenotype identification in a genetic linkage study: genome scan linkage results for longitudinal systolic blood pressure phenotypes in subjects from the Framingham Heart Study. BMC Genetics, 4(Suppl. 1), S83.

Engelman, C.D., Brady, H.L., Baron, A.E., & Norris, J.M. (2003). Comparison between two analytic strategies to detect linkage to obesity with genetically determined age of onset: the Framingham Heart Study. BMC Genetics, 4(Suppl. 1), S90.
View publication via DOI: DOI:10.1186/1471-2156-4-S1-S90

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