Cure Alzheimer's Fund Cure Alzheimer's Fund

Christoph Lange, Ph.D.

Professor of Biostatistics; Assistant Professor of Medicine, Harvard Medical School, Harvard T.H. Chan School of Public Health

I am a Professor of Biostatistics at the Harvard School of Public Health, with a joint appointment as an Assistant Professor of Medicine in the Channing Division of Medicine at Brigham and Women’s Hospital and Harvard Medical School. I am an expert in many areas of statistical genetics, with particular expertise derived from my knowledge of family-based association designs and the development and application of methods utilizing family-based association testing in studies using genome-wide association data and sequence analysis. I am a frequent collaborator of investigators in Alzheimer’s genetics and the Systems Genetics and Genomics Unit (SGGU) of the Channing Division of Network Medicine. I have served as a senior biostatistician on several large, ongoing Alzheimer’s Disease and SGGU projects which are focused on asthma and COPD genetics and epidemiology. I work with some of the most productive and innovative researchers in the field of causal inference and mediation, which allowed me to analyze the causal relationship in associations of genetic determinants with lung cancer and smoking behavior. In addition to this work in lung phenotypes, I also have long-standing expertise in statistical genetics and epidemiology of mental health phenotypes. As a faculty member, I have mentored over 10 post-doctoral fellows and have been the primary thesis and research advisor to 9 pre-doctoral students and Ph.D. candidates.

Related Research:

Moving the Cure Alzheimer’s Fund Alzheimer’s Genome Project™ Beyond Simple Associations: Integrating Functional Information, Fine-Mapping and Causal Inference Approaches into the Family-Based Analysis of the Cure Alzheimer’s Fund Whole-Genome Sequencing (WGS) Family Study Christoph Lange 2024-02-01 Precision Medicine Prediction Model for Alzheimer’s Disease Using Cooperative Learning Approaches for Multi-Omic Data Christoph Lange 2023-05-02 Genetic Ancestry-Specific Risk Estimation of Alzheimer’s Disease in the APOE Region Christoph Lange 2023-03-21 Analytical and Statistical Tools for Sequence Analysis for Alzheimer’s Disease Christoph Lange 2023-02-28 Analytical and Statistical Tools for Sequence Analysis for Alzheimer’s Disease Christoph Lange 2015-06-29

Funded Research

These projects were made possible from Cure Alzheimer's Fund support.

Project Description Researchers Funding
Moving the Cure Alzheimer’s Fund Alzheimer’s Genome Project™ Beyond Simple Associations: Integrating Functional Information, Fine-Mapping and Causal Inference Approaches into the Family-Based Analysis of the Cure Alzheimer’s Fund Whole-Genome Sequencing (WGS) Family Study 2024, 2025

$460,000
Precision Medicine Prediction Model for Alzheimer’s Disease Using Cooperative Learning Approaches for Multi-Omic Data 2023, 2024

$337,315
Genetic Ancestry-Specific Risk Estimation of Alzheimer’s Disease in the APOE Region 2023

$40,250
Analytical and Statistical Tools for Sequence Analysis for Alzheimer’s Disease 2021, 2023

$464,567
Analytical and Statistical Tools for Sequence Analysis for Alzheimer’s Disease 2015 to 2020

$1,244,023

Selected Publications

These published papers resulted from Cure Alzheimer’s Fund support.

Lee, S., Kelly, R. S., Chen, Y., Waqas, M., Mendez, K. M., Hecker, J., Hahn, G., Lutz, S. M., Celedón, J. C., Clish, C. B., Litonjua, A. A., Chen, Q., McGeachie, M., Choi, Y., Weiss, S. T., Tanzi, R. E., Lange, C., Prokopenko, D., Lasky-Su, J. A., & NHLBI Trans-Omics for Precision Medicine (TOPMed) Associations of APOE variants with sphingomyelin and cholesterol metabolites across the life-course in diverse populations, Metabolomics, May 7, 2025, Read More

Lee, S., Kelly, R. S., Mendez, K. M., Prokopenko, D., Hahn, G., Lutz, S. M., Celedón, J. C., Clish, C. B., Weiss, S. T., Lange, C., Lasky-Su, J. A., Hecker, J., & NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium On the analysis of metabolite quantitative trait loci: Impact of different data transformations and study designs, Science Advances, April 11, 2025, Read More

Ngai, T., Willett, J., Waqas, M., Fishbein, L. H., Choi, Y., Hahn, G., Mullin, K., Lange, C., Hecker, J., Tanzi, R. E., & Prokopenko, D. Assessing polyomic risk to predict Alzheimer’s disease using a machine learning model, Alzheimer's & Dementia, November 7, 2024, Read More

Hecker, J., Weiss, S. T., Lasky-Su, J. A., DeMeo, D. L., & Lange, C. Letter to the editor: critical evaluation of the reliability of DNA methylation probes on the illumina MethylationEPIC v1.0 BeadChip microarrays, Epigenetics, October 4, 2024, Read More

Hahn, G., Prokopenko, D., Hecker, J., Lutz, S. M., Mullin, K., Tanzi, R. E., DeSantis, S., & Lange, C. Polygenic hazard score models for the prediction of Alzheimer’s free survival using the lasso for Cox’s proportional hazards model, Genetic Epidemiology, July 9, 2024, Read More

Hahn, G., Prokopenko, D., Hecker, J., Lutz, S. M., Mullin, K., Sejour, L., Hide, W., Vlachos, I., DeSantis, S., Tanzi, R. E., & Lange, C. Prediction of disease-free survival for precision medicine using cooperative learning on multi-omic data, Briefings in Bioinformatics, June 5, 2024, Read More

Lee, S., Hecker, J., Hahn, G., Mullin, K., Alzheimer's Disease Neuroimaging Initiative (ADNI), Lutz, S. M., Tanzi, R. E., Lange, C., & Prokopenko, D. On the effect heterogeneity of established disease susceptibility loci for Alzheimer’s disease across different genetic ancestries, Alzheimer's & Dementia, April 2, 2024, Read More

Lee, S., Lasky-Su, J., Won, S., Laurie, C., Celedón, J. C., Lange, C., Weiss, S., & Hecker, J. Novel recessive locus for body mass index in childhood asthma, Thorax, April 22, 2021, Read More

Lee, S., Lasky-Su, J. A., Lange, C., Kim, W., Kumar, P. L., McDonald, M. N., Vaz Fragoso, C. A., Laurie, C., Raby, B. A., Celedón, J. C., Cho, M. H., Won, S., Weiss, S. T., Hecker, J., & NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium A novel locus for exertional dyspnoea in childhood asthma, The European respiratory journal, February 4, 2021, Read More

Hecker, J., Prokopenko, D., Lange, C., & Fier, H. L. On the Recombination Rate Estimation in the Presence of Populaion Substructure, PLoS One, December 30, 2015, Read More

Lutz, S. M., Sordillo, J. E., Hokanson, J. E., Chen Wu, A., & Lange, C. The effects of misspecification of the mediator and outcome in mediation analysis, Genetic Epidemiology, March 13, 2020, Read More

Prokopenko, D., Hecker, J., Silverman, E. K., Pagano, M., Nöthen, M. M., Dina, C., Lange, C., & Fier, H. L. Utilizing the Jaccard index to reveal population stratification data: a simulation study and an application ot the 1000 Genome Project, Bioinformatics, May 1, 2016, Read More

Schlauch, D., Fier, H., & Lange, C. Identification of genetic outliers due to sub-structure and cryptic relationships, Bioinformatics, March 3, 2017, Read More

Hecker, J., Prokopenko, D., Lange, C., & Fier, H. L. PolyGEE: A generalized estimating equation approach to the efficient and robust estimation of polygenic effects in large-scale association studies, Biostatistics, July 1, 2018, Read More

Hecker, J., Lee, S., Kachroo, P., Prokopenko, D., Maaser-Hecker, A., Lutz, S. M., Hahn, G., Irizarry, R., Weiss, S. T., DeMeo, D. L., & Lange, C. A consistent pattern of slide effects in Illumina DNA methylation BeadChip array data, Epigenetics, September 23, 2023, Read More

Lee, S., Prokopenko, D., Kelly, R. S., Lutz, S., Ann Lasky-Su, J., Cho, M. H., Laurie, C., Celedón, J. C., Lange, C., Weiss, S. T., Hecker, J., & DeMeo, D. L. Zinc finger protein 33B demonstrates sex interaction with atopy-related markers in childhood asthma, European Respiratory Journal, January 6, 2023, Read More

Hecker, J., Xu, X., Townes, F. W., Loehlein Fier, H., Corcoran, C., Laird, N., & Lange, C. Family-based tests for associating haplotypes with general phenotype data, Genetic Epidemiology, November 21, 2017, Read More

Hahn, G., Lee, S., Weiss, S. T., & Lange, C. Unsupervised cluster analysis of SARS-CoV-2 genomes reflects its geographic progression and identifies distinct genetic subgroups of SARS-CoV-2 virus, Genetic Epidemiology, January 8, 2021, Read More

Hecker, J., Ruczinski, I., Cho, M. H., Silverman, E. K., Coull, B., & Lange, C. A flexible and nearly optimal sequential testing approach to randomized testing: QUICK-STOP, Genetic Epidemiology, November 11, 2019, Read More

Zhou, J. J., Cho, M. H., Lange, C., Lutz, S., Silverman, E. K., & Laird, N. M. Integrating mulitple correlated phenotypes for genetic association analysis by maximizing heritability, Human Heredity, June 20, 2015, Read More

Lee, S., Lasky-Su, J., Kim, W., Won, S., Laurie, C., Celedón, J. C., Lange, C., Weiss, S. T., & Hecker, J. An interaction of the 17q12-21 locus with mold exposure in childhood asthma, Pediatric Allergy and Immunology, September 18, 2020, Read More

Prokopenko, D., Hecker, J., Silverman, E., Nöthen, M. M., Schmid, M., Lange, C., & Loehlein Fier, H. Using Network Methodology to infer population substructure, PLoS One, June 22, 2015, Read More

Hecker, J., Townes, F. W., Kachroo, P., Laurie, C., Lasky-Su, J., Ziniti, J., Cho, M. H., Weiss, S. T., Laird, N. M., & Lange, C. A unifying framework for rare variant association testing in family-based designs, including higher criticism approaches, SKATs, and burden tests, Bioinformatics, December 26, 2020, Read More

Lutz, S. M., Voorhies, K., Wu, A. C., Hokanson, J., Vansteelandt, S., & Lange, C. Selection bias when inferring the effect direction in Mendelian randomization, Genetic Epidemiology, May 2, 2022, Read More

Hecker, J., Laird, N., & Lange, C. A Comparison of Popular TDT-generalizations for family-based association analysis, Genetic Epidemiology, January 4, 2019, Read More

Hahn, G., Lutz, S. M., Hecker, J., Prokopenko, D., Cho, M. H., Silverman, E. K., Weiss, S. T., & Lange, C. Fast computation of the eigensystem of genomic similarity matrices, BMC Bioinformatics, January 25, 2024, Read More

Prokopenko, D., Lee, S., Hecker, J., Mullin, K., Morgan, S., Katsumata, Y., Alzheimer’s Disease Neuroimaging Initiative (ADNI), Weiner, M. W., Fardo, D. W., Laird, N., Bertram, L., Hide, W., Lange, C., & Tanzi, R. E. Region-based analysis of rare genomic variants in whole-genome sequencing datasets reveal two novel Alzheimer’s disease-associated genes: DTNB and DLG2, Molecular Psychiatry, March 4, 2022, Read More

Hahn, G., Prokopenko, D., Lutz, S. M., Mullin, K., Tanzi, R. E., Cho, M. H., Silverman, E. K., Lange, C., & On The Behalf Of The Nhlbi Trans-Omics For Precision Medicine TOPMed Consortium A Smoothed Version of the Lassosum Penalty for Fitting Integrated Risk Models Using Summary Statistics or Individual-Level Data, Genes, January 6, 2022, Read More

Prokopenko, D., Morgan, S. L., Mullin, K., Hofmann, O., Chapman, B., Kirchner, R., Alzheimer's Disease Neuroimaging Initiative (ADNI), Amberkar, S., Wohlers, I., Lange, C., Hide, W., Bertram, L., & Tanzi, R. E. Whole-genome sequencing reveals new Alzheimer’s disease-associated rare variants in loci related to synaptic function and neuronal development, Alzheimer's & Dementia, April 2, 2021, Read More

Prokopenko, D., Hecker, J., Kirchner, R., Chapman, B. A., Hoffman, O., Mullin, K., Hide, W., Bertram, L., Laird, N., DeMeo, D. L., Lange, C., & Tanzi, R. E. Identification of Novel Alzheimer’s Disease Loci Using Sex-Specific Family-Based Association Analysis of Whole-Genome Sequence Data, Scientific Reports, March 19, 2020, Read More

Loehlein Fier, H., Prokopenko, D., Hecker, J., Cho, M. H., Silverman, E. K., Weiss, S. T., Tanzi, R. E., & Lange, C. On the association analysis of genome-sequencing data: A spatial clustering approach for partitioning the entire genome into nonoverlapping windows, Genetic Epidemiology, April 20, 2017, Read More

Park, S., Lee, S., Lee, Y., Herold, C., Hooli, B., Mullin, K., Park, T., Park, C., Bertram, L., Lange, C., Tanzi, R., & Won, S. Adjusting heterogeneous ascertainment bias for genetic association analysis with extended families, BMC Medical Genetics, August 19, 2015, Read More

Hooli, B. V., Kovacs-Vajna, Z. M., Mullin, K., Blumenthal, M. A., Mattheisen, M., Zhang, C., Lange, C., Mohapatra, G., Bertram, L., & Tanzi, R. E. Rare autosomal copy number variations in early-onset familial Alzheimer’s disease, Molecular Psychiatry, June 11, 2013, Read More

Hooli, B. V., Mohapatra, G., Mattheisen, M., Parrado, A. R., Roehr, J. T., Shen, Y., Gusella, J. F., Moir, R., Saunders, A. J., Lange, C., Tanzi, R. E., & Bertram, L. Role of common and rare APP DNA sequence variants in Alzheimer’s Disease, Neurology, April 17, 2012, Read More

Schjeide, B. M., McQueen, M. B., Mullin, K., DiVito, J., Hogan, M. F., Parkinson, M., Hooli, B., Lange, C., Blacker, D., Tanzi, R. E., & Bertram, L. Assessment of Alzheimer’s disease case-control associations using family-based methods, Neurogenetics, February 1, 2009, Read More

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