Current Research Interests:
Genes of Brain Disorders
After the Human Genome was characterized end of last century, now the decade of the brain has arrived. We are using genetic information to find the genes involved in brain disorders, then dissect the disease process, often in animal models. We have identified deafness and other neurological disorder genes and now focus on ataxias as well as behavior and psychiatric diseases.
There are at least 60 known ataxia genes, some of which our lab discovered. Our pipeline starts with recruitment of families with rare disorders, then combines genetic (linkage) information with genome-wide gene expression and next generation sequencing. By combining these approaches, we could identify genes involved in ataxias, and are actively recruiting additional families with rare neurological disorders.
Human behavior and risk for psychiatric illness such as depression and alcoholism are determined by a complex interaction of environmental and multiple genetic risk factors. With the Human Genome sequenced, unprecedented numbers of genetic variants identified, and novel technologies that allow the study of genetic variants, untangling these risk factors is now possible, using genome-wide association studies (GWAS) and next generation sequencing. For most complex disorders, considering the environment as well as the genetic susceptibility is essential to fully understand their function.
In addition to genetic risk factors for bipolar disorder and for addiction, we also investigate genetic variants that influence traits related to psychiatric disorders: High anxiety or feeling vulnerable (neuroticism) is a marker for depression risk, and high impulsivity and low executive function are risk factor for addictions. These and other endophenotypes such as neuroimaging processes in the brain start explaining the path from genetic variant to behavioral outcome.
We collaborate with clinicians, psychologists, epidemiologists, statisticians and bioinformaticians as well as other geneticists in these endeavors.
- Co-Director, Bioinformatics graduate program, Center for Computational Medicine and Bioinformatics
- Faculty member of interdisciplinary graduate programs: Neuroscience, Cell & Molecular Biology.
- Diplom (Master) in Biochemistry, Free University of Berlin and Weizman Institute of Science, Rehovot, Israel.
- Ph.D., European Molecular Biology Laboratory (EMBL) and University of Heidelberg.
- Postdoctoral Fellow, University of California San Francisco.
Honors and Awards:
Distinguished Professor, Bio-X Center, Shanghai Jiao Tong University, China
Michael Weston Visiting Professorship, Weizmann Inst. of Science, Rehovot, Israel
Fellow of the "Studienstiftung des Deutschen Volkes" (German Phi Beta Kappa Equivalent).
Postdoctoral Fellowship from the German Academic Exchange Committee (DAAD).
NARSAD Distinguished Investigator Award 2008 and many earlier NARSAD awards
Klingenstein Fellowship Award in the Neurosciences.
Alexander von Humboldt Foundation Fellowship for Sabbatical in Berlin, Germany.
Greenwald MK, Steinmiller CL, Sliwerska E, Lundahl L, Burmeister M: BDNF Val66Met Genotype is Associated with Drug-Seeking Phenotypes in Heroin-Dependent Individuals. Addiction Biology, in press.
Villafuerte S, Strumba V, Stoltenberg S, Zucker RA, Burmeister M: Impulsiveness mediates the association between GABRA2 SNPs and lifetime of alcohol-related problems. Genes, Brain & Behavior, in press.
Lee YC*, Durr A*, Majczenko K*, Huang YH, Liu YC, Lien CC, Ichikawa Y, Goto J, Monin ML, Li JZ, Chung MY, Mundwiller E, Shakkottai K, Liu TT, Tesson C, Lu YC, Tsai PC, Brice A, Tsuji S, Burmeister M*, Stevanin G*, Soong BW*: Mutations in KCND3 cause spinocerebellar ataxia type 22. Annals Neurol 72(6):859-69
Guan YF, Gorenshteyn D, Burmeister M, Schimenti JC, Handel MA, Bult CA, Hibbs, MA, Troyanskaya OG: Tissue-specific functional networks for prioritizing phenotype and disease genes, PLoS Comput Biol. Sep;8(9):e1002694, 2012.
Zhang Y, Li J, Tardif T, Burmeister M, Villafuerte SM, McBride-Chang C, Li H, Shi N, Liang W, Zhang Z, Shu H: Association of the DYX1C1 dyslexia susceptibility gene with orthography in the Chinese population. PLoS ONE 7(9):e42969, 2012.
Majczenko K*, Davidson A*, Li X, Joshi SJ, Beggs AH, Li, J., Burmeister M*, and Dowling JJ*. Dominant mutation in CCDC78 in a novel congenital myopathy with cores, Am. J. Hum. Genet. 91(2):365-71, 2012.
Brower KJ, Wojnar M, Sliwerska E, Armitage R, Burmeister M: PER3 Polymorphism and Insomnia Severity in Alcohol Dependence. Sleep, 35(4):571-7, 2012.
Villafuerte S, Heitzeg MM, Foley S, Yau WYW, Majczenko K, Zubieta JK, Zucker RA, Burmeister M: Impulsiveness and Insular activation during reward anticipation are associated with genetic variants in GABRA2 in a family sample enriched for alcoholism. Molecular Psychiatry17(5):511-9, 2012.
Schoen CJ, Emery SB, Thorne MC, Ammana HR, Sliwerska E, Arnett J, Hortsch M, Hannan F, Burmeister M, Lesperance MM Increased activity of Diaphanous homolog 3 (DIAPH3)/diaphanous causes hearing defects in humans with auditory neuropathy and in Drosophila, Proc Natl Acad Sci U S A. 2010 Jul 12. [Epub ahead of print]
Wojnar M, Brower KJ, Strobbe S, Ilgen M, Matsumoto H, Nowosad I, Sliwerska E, Burmeister M. Association Between Val66Met Brain-Derived Neurotrophic Factor (BDNF) Gene Polymorphism and Post-Treatment Relapse in Alcohol Dependence. Alcohol Clin Exp Res 33: 693-702, 2009.
Scott LJ, Muglia P, Kong XQ, Guan W, Flickinger M, Upmanyu R, Tozzi F, Li JZ, Burmeister M, Absher D, Thompson RC, Francks C, Meng F, Antoniades A, Southwick AM, Schatzberg AF, Bunney WE, Barchas JD, Jones EG, Day R, Matthews K, McGuffin P, Strauss JS, Kennedy JL, Middleton L, Roses AD, Watson SJ, Vincent JB, Myers RM, Farmer AE, Akil H, Burns DK, Boehnke M. Genome-wide association and meta-analysis of bipolar disorder in individuals of European ancestry. Proc Natl Acad Sci U S A 106(18):7501-6, 2009.
Li MD, Burmeister M: New insights into the genetics of addiction. Nat Rev Genet. 2009 Apr;10(4):225-31.
Burmeister, M, McInnis, MG, and Zoellner S: Psychiatric Genetics – Progress Amid Controversy. Nature Reviews Genetics 9: 527-540, 2008.
Links to additional information about the work of Dr. Burmeister.
Department of Psychiatry, University of Michigan
Department of Human Genetics, University of Michigan
Department of Computational Medicine & Bioinformatics
Bioinformatics Graduate Program
Figure 1: Pipeline for Identification of Rare Disorder genes used in the lab.
Figure 2: Multiple risk factors for depression
Depression is thought to be caused by a combination of genetic factors, early experiences and stressful life events. Instead of comparing depressed subjects and controls, research on the genetics of personality can get at genetic predisposition genes for depression even while studying a general population sample.
Figure 3: Psychiatric disorders overlap and might be extremes of personality traits.
Genetic vulnerabilities for psychiatric disorders are shown as emerging from the extreme end of normal population variations of personality, illustrated as different background shades of mood, anxiety, cognitive processing and volition. Genetic factors affecting levels of these underlying traits, in interaction with additional genetic and environmental factors, can lead to psychiatric disorders — shown here are bipolar disorder, schizophrenia, depression and anxiety disorders — the symptoms and genetic risk factors of which are in part unique and in part overlapping. Because not all disorders can be covered in two dimensions, interactions and overlaps exist in many more dimensions than can be represented here.