Lars Bertram, M.D.

Professor of Genome Analytics, Institute for Neurogenetics, University of Lübeck, Germany

Lars Bertram graduated from medical school at Ruhr University Bochum, Germany, in 1997, and began his clinical training at the Alzheimer Centre of the Klinikum rechts der Isar in Munich. In 1999, he joined the Genetics and Aging Research Unit at Massachusetts General Hospital (MGH) and was appointed to the faculty of Harvard Medical School as Assistant Professor of Neurology in 2004. In 2008, Dr. Bertram moved back to Germany where he founded the Neuropsychiatric Genetics Group in the Department of Vertebrate Genomics at the Max-Planck Institute for Molecular Genetics (MPIMG) in Berlin. In 2014, he was appointed Professor of Genome Analytics in the Medical Faculty at University of Lübeck, Germany, where he heads the Lübeck Interdisciplinary Platform for Genome Analytics (LIGA). Since 2013, Dr. Bertram also holds an appointment as Reader in Neurogenetics at the School of Public Health, Faculty of Medicine, Imperial College London, UK.

Scientifically, Dr. Bertram's expertise lies in the mapping and characterization of complex disease genes, predominantly in the field of neuropsychiatric diseases and aging. In addition to his laboratory work, Dr. Bertram has pioneered the development of bioinformatics approaches that systematically and quantitatively integrate large-scale genetic data for phenotypes such as Alzheimer's disease, schizophrenia, Parkinson's disease, and multiple sclerosis. Currently, he is leading several projects that apply “next generation” genomics and epigenomics technologies to genetically complex traits.

Dr. Bertram has co-authored over 150 peer-reviewed scientific articles, the majority of which have been published in the leading journals of basic science, genetics, and medicine. During his career, he received numerous awards and honors, e.g. from the Harvard Center for Neurodegeneration and Repair, the ERASMUS foundation, the National Alliance on Research in Depression and Schizophrenia (NARSAD), the Alzheimer Research Forum, and the Hans & Ilse Breuer Stiftung for Alzheimer's Research.

Funded Research

Project Description Researchers Funding
CIRCUITS: Epigenetic Determinants of Human Cognitive Aging

Much like many other human traits, cognitive decline and the development of Alzheimer's disease (AD) are determined by the concerted action of genetic, epigenetic and nongenetic factors. Over the last decade, genetics research in AD has progressed at unprecedented pace owing to the application of high-throughput genotyping technologies in the context of genome-wide association studies (GWAS).

High-Throughput Multiplex Real-Time PCR For CSF-Biomarker And MicroRNA Profiling In AD

This project will fund the purchase of a high-throughput real-time PCR instrument that will allow to us to achieve two scientific goals:

i) expand the ongoing projects on AD biomarker genetics to a large, newly recruited cohort of dementia patients and healthy controls for whom both CSF biomarker data (i.e. levels of Aβ, Aβ42, tau, phospho-tau proteins) and DNA samples are already available, and

Upkeep and Maintenance of the AlzGene Database

Cure Alzheimer’s Fund is funding the upkeep and continued development of a revolutionary Web-based database. AlzGene is a fantastic resource for Alzheimer’s researchers, providing data and meta-analyses from hundreds of genetic association studies in an easy-to-use, searchable database. Scientists interested in a particular gene can search for it in AlzGene to see what previous studies have reported, receiving a wealth of information in a very short amount of time.

2006 to 2013

Fine Mapping of Prioritized GWAS Results

In this application we propose to utilize next-generation sequencing combined with high-efficiency genomic sequence capture to systematically fine-map the 14q31 region which, based on the currently available data, very likely contains an important AD susceptibility locus(i). Newly identified variants will be followed up in more than 5,500 DNAs from both family-based and case-control backgrounds.


Selected Publications

These published papers resulted from Cure Alzheimer’s Fund support.
C Herold, B V Hooli, K Mullin, T Liu, J T Roehr, M Mattheisen, A R Parrado, L Bertram, C Lange and R E Tanzi, Family-based association analyses of imputed genotypes reveal genome-wide significant association of Alzheimer’s disease with OSBPL6, PTPRG, and PDCL3, Molecular Psychiatry, February 2016
L. Schrewe, C. M. Lill, T. Liu, A. Salmen, L. A. Gerdes, L. Guillot-Noel, D. A. Akkad, P. Blaschke, C. Graetz, S. Hoffjan, A. Kroner, S. Demir, A. Böhme, P. Rieckmann, A. ElAli, N. Hagemann, D. M. Hermann, I. Cournu-Rebeix, F. Zipp, T. Kümpfel, M. Buttmann, U. K. Zettl, B. Fontaine, L. Bertram, R. Gold and A. Chan, Investigation of sex-specific effects of apolipoprotein E on severity of EAE and MS, Journal of Neuroinflammation, 12(1), December 2015, 1-7
Christina M. Lill, Aina Rengmark, Lasse Pihlstrøm, Isabella Fogh, Aleksey Shatunov, Patrick M. Sleiman, Li-San Wang, Tian Liu, Christina F. Lassen, Esther Meissner, Panos Alexopoulos, Andrea Calvo, Adriano Chio, Nil Dizdar, Frank Faltraco, Lars Forsgren, Julia Kirchheiner, Alexander Kurz, Jan P. Larsen, Maria Liebsch, Jan Linder, Karen E. Morrison, Hans Nissbrandt, Markus Otto, Jens Pahnke, Amanda Partch, Gabriella Restagno, Dan Rujescu, Cathrin Schnack, Christopher E. Shaw, Pamela J. Shaw, Hayrettin Tumani, Ole-Bjørn Tysnes, Otto Valladares, Vincenzo Silani, Leonard H. van den Berg, Wouter van Rheenen, Jan H. Veldink, Ulman Lindenberger, Elisabeth Steinhagen-Thiessen, Stefan Teipel, Robert Perneczky, Hakon Hakonarson, Harald Hampel, Christine A.F. von Arnim, Jørgen H. Olsen, Vivianna M. Van Deerlin, Ammar Al-Chalabi, Mathias Toft, Beate Ritz, Lars Bertram, The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease, Alzheimer's & Dementia, 11(12), December 2015, 1407–1416
Christina M. Lill MD, Johnni Hansen PhD, Jørgen H. Olsen MD, Harald Binder PhD, Beate Ritz MD, PhD and Lars Bertram MD, Impact of Parkinson's disease risk loci on age at onset, Movement Disorders, 30(6), May 2015, 847–850
Christina M. Lill, Marcel Schilling, Sara Ansaloni, Julia Schröder, Marian Jaedicke, Felix Luessi, Brit-Maren M. Schjeide, Andriy Mashychev, Christiane Graetz, Denis A. Akkad, Lisa-Ann Gerdes, Antje Kroner, Paul Blaschke, Sabine Hoffjan, Alexander Winkelmann, Thomas Dörner, Peter Rieckmann, Elisabeth Steinhagen-Thiessen, Ulman Lindenberger, Andrew Chan, Hans-Peter Hartung, Orhan Aktas, Peter Lohse, Mathias Buttmann, Tania Kümpfel, Christian Kubisch, Uwe K. Zettl, Joerg T. Epplen, Frauke Zipp, Lars Bertram, Assessment of microRNA-related SNP effects in the 3′ untranslated region of theIL22RA2 risk locus in multiple sclerosis, Neurogenetics, 15(2), March 18 2014, 129-134
BV Hooli1, ZM Kovacs-Vajna2, K Mullin1, MA Blumenthal1, M Mattheisen3, C Zhang1, C Lange4, G Mohapatra5, L Bertram6 and RE Tanzi1, Rare autosomal copy number variations in early-onset familial Alzheimer’s disease, Molecular Psychology, 6/11/2013
International Multiple Sclerosis Genetics Consortium, Lill CM, Schjeide BM, Graetz C, Ban M, Alcina A, Ortiz MA, Pérez J, Damotte V, Booth D, Lopez de Lapuente A, Broer L, Schilling M, Akkad DA, Aktas O, Alloza I, Antigüedad A, Arroyo R, Blaschke P, Buttmann M, Chan A, Compston A, Cournu-Rebeix I, Dörner T, Epplen JT, Fernández Ó, Gerdes LA, Guillot-Noël L, Hartung HP, Hoffjan S, Izquierdo G, Kemppinen A, Kroner A, Kubisch C, Kümpfel T, Li SC, Lindenberger U, Lohse P, Lubetzki C, Luessi F, Malhotra S, Mescheriakova J, Montalban X, Papeix C, Paredes LF, Rieckmann P, Steinhagen-Thiessen E, Winkelmann A, Zettl UK, Hintzen R, Vandenbroeck K, Stewart G, Fontaine B, Comabella M, Urcelay E, Matesanz F, Sawcer S, Bertram L, Zipp F, MANBA, CXCR5, SOX8, RPS6KB1 and ZBTB46 are genetic risk loci for multiple sclerosis, Brain, 1386 (Pt 6), June 2013, 1778-1782
Irene Pichler, Fabiola Del Greco M., Martin Gögele, Christina M. Lill, Lars Bertram, Chuong B. Do, Nicholas Eriksson, Tatiana Foroud, Richard H. Myers, PD GWAS Consortium, Michael Nalls, Margaux F. Keller, International Parkinson's Disease Genomics Consortium, Wellcome Trust Case Control Consortium, Beben Benyamin, John B. Whitfield, Genetics of Iron Status Consortium, Peter P. Pramstaller, Andrew A. Hicks, John R. Thompson, and Cosetta Minelli, Serum Iron Levels and the Risk of Parkinson Disease: A Mendelian Randomization Study, PLOS Med , 10(6), June 2013
Lill CM, Schjeide BM, Graetz C, Liu T, Damotte V, Akkad DA, Blaschke P, Gerdes LA, Kroner A, Luessi F, Cournu-Rebeix I, Hoffjan S, Winkelmann A, Touze E, Pico F, Corcia P, Otaegui D, Antigüedad A, Alcina A, Comabella M, Montalban X, Olascoaga J, Matesanz F, Dörner T, Li SC, Steinhagen-Thiessen E, Lindenberger U, Chan A, Rieckmann P, Hartung HP, Aktas O, Lohse P, Buttmann M, Kümpfel T, Kubisch C, Zettl UK, Epplen JT, Fontaine B, Zipp F, Vandenbroeck K, Bertram L, Genome-wide significant association of ANKRD55 rs6859219 and multiple sclerosis risk, J Med Genet, 50(30), January 12, 2013, 140-143
Lill CM, Bertram L, Developing the ‘next generation’ of genetic association databases for complex diseases, Hum. Mutat., 33(9), September 2012, 1366–72
Lill CM, Liu T, Schjeide BM, Roehr JT, Akkad DA, Damotte V, Alcina A, Ortiz MA, Arroyo R, Lopez de Lapuente A, Blaschke P, Winkelmann A, Gerdes LA, Luessi F, Fernadez O, Izquierdo G, Antigüedad A, Hoffjan S, Cournu-Rebeix I, Gromöller S, Faber H, Liebsch M, Meissner E, Chanvillard C, Touze E, Pico F, Corcia P; ANZgene Consortium, Dörner T, Steinhagen-Thiessen E, Baeckman L, Heekeren HR, Li SC, Lindenberger U, Chan A, Hartung HP, Aktas O, Lohse P, Kümpfel T, Kubisch C, Epplen JT, Zettl UK, Fontaine B, Vandenbroeck K, Matesanz F, Urcelay E, Bertram L, Zipp F, Closing the case of APOE in multiple sclerosis: no association with disease risk in over 29,000 subjects, J Med Genet., 49(9), September 2012, 558-62
Wallace BC, Small K, Brodley CE, Lau J, Schmid CH, Bertram L, Lill CM, Cohen JT, Trikalinos TA, Toward modernizing the systematic review pipeline in genetics: efficient updating via data mining, Genet Med., 14(7), July 2012, 663-9
B.V. Hooli, PhD, G. Mohapatra, PhD, M. Mattheisen, MD, A.R. Parrado, PhD, J.T. Roehr, MS, Y. Shen, PhD, J.F. Gusella, PhD, R. Moir, PhD, A.J. Saunders, PhD, C. Lange, PhD, R.E. Tanzi, PhD and L. Bertram, MD, Role of common and rare APP DNA sequence variants in Alzheimer disease, Neurology 78 , 78/16, April 17, 2012, 1250-1257
Lill CM, Roehr JT, McQueen MB, Kavvoura FK, Bagade S, Schjeide BM, Schjeide LM, Meissner E, Zauft U, Allen NC, Liu T, Schilling M, Anderson KJ, Beecham G, Berg D, Biernacka JM, Brice A, DeStefano AL, Do CB, Eriksson N, Factor SA, Farrer MJ, Foroud T, Gasser T, Hamza T, Hardy JA, Heutink P, Hill-Burns EM, Klein C, Latourelle JC, Maraganore DM, Martin ER, Martinez M, Myers RH, Nalls MA, Pankratz N, Payami H, Satake W, Scott WK, Sharma M, Singleton AB, Stefansson K, Toda T, Tung JY, Vance J, Wood NW, Zabetian CP; 23andMe Genetic Epidemiology of Parkinson's Disease Consortium; International Parkinson's Disease Genomics Consortium; Parkinson's Disease GWAS Consortium; Wellcome Trust Case Control Consortium 2), Young P, Tanzi RE, Khoury MJ, Zipp F, Lehrach H, Ioannidis JP, Bertram L, Comprehensive research synopsis and systematic meta-analyses in Parkinson’s disease genetics: The PDGene database, PLoS Genet., 8(3), March 2012, e1002548
Lill CM, Schjeide BM, Akkad DA, Blaschke P, Winkelmann A, Gerdes LA, Hoffjan S, Luessi F, Dörner T, Li SC, Steinhagen-Thiessen E, Lindenberger U, Chan A, Hartung HP, Aktas O, Lohse P, Kümpfel T, Kubisch C, Epplen JT, Zettl UK, Bertram L, Zipp F, Independent replication of STAT3 association with multiple sclerosis risk in a large German case-control sample, Neurogenetics, 13(1), February 2012, 83-6
Sungho Wona, Qing Luc, Lars Bertram, Rudolph E. Tanzi, Christoph Lange, On the Meta-Analysis of Genome-Wide Association Studies: A Robust and Efficient Approach to Combine Population and Family-Based Studies, Human Heredity , 73, January 18, 2012, 35-46
Lebedeva E, Stingl JC, Thal DR, Ghebremedhin E, Strauss J, Özer E, Bertram L, von Einem B, Tumani H, Otto M, Riepe MW, Högel J, Ludolph AC, von Arnim CA, Genetic variants in PSEN2 and correlation to CSF β-amyloid42 levels in AD, Neurobiol Aging, 33(1), January 2012, 201.e9-201.e18
Bertram L, Hampel H, The role of genetics for biomarker development in neurodegeneration, Prog Neurobiol., 95(4), December 2011, 501-4
Lill CM, Bertram L, Towards unveiling the genetics of neurodegenerative diseases, Semin Neurol., 31(5), November 2011, 531-41
Haworth A, Bertram L, Carrera P, Elson JL, Braastad CD, Cox DW, Cruts M, den Dunnen JT, Farrer MJ, Fink JK, Hamed SA, Houlden H, Johnson DR, Nuytemans K, Palau F, Rayan DL, Robinson PN, Salas A, Schüle B, Sweeney MG, Woods MO, Amigo J, Cotton RG, Sobrido MJ, Call for participation in the neurogenetics consortium within the Human Variome Project, Neurogenetics, 12(3), August 2011, 169-73
Bertram, L, Alzheimer’s genetics in the GWAS era: a continuing story of ‘replications and refutations’, Curr Neurol Neurosci Rep., 11(3), June 2011, 246-53
Sarajärvi T, Tuusa JT, Haapasalo A, Lackman JJ, Sormunen R, Helisalmi S, Roehr JT, Parrado AR, Mäkinen P, Bertram L, Soininen H, Tanzi RE, Petäjä-Repo UE, Hiltunen M, Cysteine 27 Variant of the δ-Opioid Receptor Affects Amyloid Precursor Protein Processing through Altered Endocytic Trafficking, Mol Cell Biol., 31(11), June 2011, 2326–2340
Thomas Pfeiffer, Lars Bertram, John P. A. Ioannidis, Quantifying Selective Reporting and the Proteus Phenomenon for Multiple Datasets with Similar Bias, Plos One, 6:3 , March 29, 2011
Brit-Maren M. Schjeide, BS; Cathrin Schnack, PhD; Jean-Charles Lambert, PhD; Christina M. Lill, MD; Julia Kirchheiner, MD, PhD; Hayrettin Tumani, MD; Markus Otto, MD; Rudolph E. Tanzi, PhD; Hans Lehrach, PhD; Philippe Amouyel, PhD; Christine A. F. von Arnim, MD; Lars Bertram, MD, The Role of Clusterin, Complement Receptor 1, and Phosphatidylinositol Binding Clathrin Assembly Protein in Alzheimer Disease Risk and Cerebrospinal Fluid Biomarker Levels, Arch Gen Psychiatry, 68(2), February 7, 2011, 207-213
Bertram L, Lill CM, Tanzi RE, The Genetics of Alzheimer Disease: Back to the Future, Neuron, 68(2), Oct 21, 2010, 270-81
Dolan SM, Hollegaard MV, Merialdi M, Betran AP, Allen T, Abelow C, Nace J, Lin BK, Khoury MJ, Ioannidis JP, Bagade S, Zheng X, Dubin RA, Bertram L, Velez Edwards DR, Menon R, Synopsis of preterm birth genetic association studies: the preterm birth genetics knowledge base (PTBGene), Public Health Genomics, 13(7-8), May 20, 2010, 514-23
Sleegers K, Lambert J-C, Bertram L, Cruts M, Amouyel P, Broeckhoven CV, The pursuit of susceptibility genes for Alzheimer's disease: progress and prospects, Trends in Genetics, Volume 26, Issue 2, February 2010, 84-93
Castaldi PJ, Cho MH, Cohn M, Langerman F, Moran S, Tarragona N, Moukhachen H, Venugopal R, Hasimja D, Kao E, Wallace B, Hersh CP, Bagade S, Bertram L, Silverman EK, Trikalinos TA, The COPD genetic association compendium: a comprehensive online database of COPD genetic associations, Hum. Mol. Genet., 10.1093/hmg/ddp519, Feb 1, 2010
Giedraitis V, Glaser A, Sarajarvi T, Brundin R, Gunnarsson MD, Schjeide B-M, Tanzi RE, Helisalmi S, Pirttila T, Kilander L, Lannfelt L, Soininen H, Bertram L, Ingelsson M, Hiltunen M, CALHM1 P86L polymorphism does not alter amyloid-β or tau in cerebrospinal fluid, Neuroscience Letters, Volume 469, Issue 2, Jan 22 2010, 265-267
Lill CM, Bertram L, Online databases and systematic meta-analyses of genetically complex diseases, Medizin Genet, 22, 2010, 235-241
Won S, Bertram L, Becker D, Tanzi RE, Lange C., Maximizing the Power of Genome-Wide Association Studies: A Novel Class of Powerful Family - Based Association Tests, Statistics in Biosciences, 1(2), Nov 2009, 125-143
Bertram, L, Tanzi RE, Genome-wide association studies in Alzheimer's disease, Human Molecular Genetics, Vol 18, Review Issue 2, Oct 15, 2009
Bertram L, Alzheimer's Disease Genetics: Current Status and Future Perspectives, International Review of Neurobiology, Vol. 84, 2009
Schjeide BM, McQueen MB, Mullin K, DiVito J, Hogan MF, Parkinson M, Hooli B, Lange C, Blacker D, Tanzi RE, and Bertram L., Assessment of Alzheimer's disease case-control associations using family-based methods, Neurogenetics, DOI 10.1007/s10048-008-1051-3,, Feb 10, 2009, 568-580
Schjeide BM, Hooli B, Parkinson M, Hogan MF, DiVito J, Mullin K, Blacker D, Tanzi RE, Bertram L, GAB2 as an Alzheimer Disease Susceptibility Gene, Follow up of Genomewide Association Results, Arch Neurol, 66, Feb 2009, 250 – 254
Bertram L, Schjeide BM, Hooli B, Mullin K, Hiltunen M, Soininen H, Ingelsson M, Lannfelt L, Blacker D, Tanzi RE., No association between CALHM1 and Alzheimer's disease risk., Cell, 135(6), Dec 12 2008, 993-4
Bertram L, Lange CL, Mullin K, Parkinson M, Hsiao M, Hogan MF,  Schjeide BMM, Hooli B, DeVito J, Ionita I, Jiang H, Laird N, Moscarillo T, Ohlsen KL, Elliott K, Wang X, Hu-Lince D, Ryder M, Murphy A, Wagner SL, Blacker D, Becker KD, Tanzi RE., Genome-wide Association Analysis Reveals Putative Alzheimer's Disease Susceptibility Loci in Addition to APOE, Am. J. Hum. Genet., 83, November 2008, 623-632
Schaffer B, Bertram L, Miller L, Mullin K, Weintraub S, Johnson N, Bigio E, Mesulam M, Wiedau-Pazos M, Jackson G, Cummings J, Cantor R, Levey A, Tanzi RE, and Geschwind D, Association of GSK3B with Alzheimer's Disease and Frontotemporal Dementia, Arch. Neurol., 65(10), October 2008, 1368-1374
Bertram L, Tanzi RE, Thirty years of Alzheimer’s disease genetics: the implications of systematic meta-analyses, Nature Reviews Neurosci., October 2008
Kim M, Hersh LB, Leissring MA, Ingelsson M, Matsui T, Farris W, Lu A, Hyman BT, Selkoe DJ, Bertram L, Tanzi RE, Decreased catalytic activity of the insulin degrading enzyme in chromosome 10-linked Alzheimer’s disease families., Journal of Biological Chemistry, 282(11), 2007, 7825-32
McQueen MB, Bertram L, Lange C, Becker KD, Albert MS, Tanzi RE, Blacker D., Exploring Candidate Gene Associations with Neuropsychological Performance., Am J Med Genet B Neuropsychiatr Genet, 144(8), 2007, 987-91