BBS Faculty Member - Steven McCarroll

Steven McCarroll

Department of Genetics

Harvard Medical School
NRB 260
77 Avenue Louis Pasteur
Boston, MA 02115
Tel: 617-432-7794
Fax: 617-432-6306
Visit my lab page here.

We are interested in (i) how the human genome varies from person to person, across and within human populations; and (ii) how genome variation affects molecular phenotypes in cells and tissues on its way to influencing disease risk in populations. We are particularly interested in how genome variation influences gene expression in neurons on its way to affecting brain phenotypes such as risk of bipolar disorder and schizophrenia.

We use experimental and computational methods in integrative ways. Almost all of the projects in the lab draw upon experimental, computational, and statistical approaches at the same time.

We have found that human genomes vary at large scales in the form of the deletion, duplication, and rearrangement of long genomic segments consisting of hundreds of thousands of base pairs. We developed molecular tools for identifying such "structural" variation from genomic DNA, and computational approaches for identifying such variation from genome-wide sequence data sets. We have found that some of these large-scale structural variants are strong risk factors for schizophrenia, autism, and other clinical phenotypes. Intriguingly, we have also found that many other structural polymorphisms are part of the reservoir of normal, inherited genome polymorphism that segregates in human populations. Both kinds of variants are teaching us about genome evolution, functional variation in genome sequence, and the inherited basis of complex phenotypes in humans.

Mental illness presents a particularly challenging, interesting and important problem for the genetics of complex disease. Schizophrenia and bipolar disorder have enormous public health impact, yet there is little if any understanding of these disorders at a molecular or cellular level. Both disorders are highly heritable, suggesting that insights about the underlying biology might be reached via our genomes. We have been working to find genetic influences of risk of these disorders using genome-wide genotyping and sequencing in large cohorts of patients. Having found many genetic influences on risk of these disorders, we then set out to understand what biological perturbations arise from these genetic variants – what genes and proteins are affected, and in what populations of cells, and how the molecular biology of these cells is perturbed by genetic polymorphism. Our goal is to use genetics to reveal the molecular pathophysiology of these disorders and generate new ideas for therapeutics.

I am a faculty member in the Department of Genetics at Harvard Medical School. I also serve as Director of Genetics for the Broad Institute's Stanley Center for Psychiatric Research.

Last Update: 8/22/2013


For a complete listing of publications click here.



Boettger L.M., Handsaker R.E., Zody M.C., McCarroll S.A. Structural haplotypes and recent evolution of the human 17q21.31 locus. Nature Genetics, 10/1038/ng/2334, 2012.

Handsaker RE, Korn JM, Nemesh J, McCarroll SA. Discovery and genotyping of genome structural polymorphism by sequencing on a population scale. Nature Genetics 43: 269-76, 2011.

Macosko EZ, McCarroll SA. Exploring the genome variation within each organism. Nature Genetics 44: 614-16, 2012.

McCarroll SA, Kuruvilla FG, Korn JM, Cawley S, Nemesh J, Wysoker A, Shapero MH, deBakker PIW, Maller J, Kirby A, Elliott AL, Parkin M, Hubbell E, Webster T, Mei R, Veitch J, Collins PJ, Handsaker R, Lincoln S, Nizzari M, Blume J, Jones K, Rava R, Daly MJ, Gabriel SB, Altshuler DM. Integrated detection and population genetic analysis of SNPs and copy number variation. Nature Genetics 40:1166-74, 2008.

McCarroll SA, Huett AS, Kuballa P, Chilewski S, Landry A, Goyette P, Zody MC, Hall JL, Brant SR, Cho JH, Duerr RH, Silverberg MS, Taylor KD, Rioux JD, Altshuler D, Daly MJ, Xavier RJ. Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn’s disease. Nature Genetics 40:1107-1112, 2008.

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