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Recent papers have suggested that duplications and deletions of large segments of DNA from patients with schizophrenia, ADHD, and other psychiatric illnesses are linked to genes involved in brain development. Soumya Raychaudhuri and his colleagues at the ӳ����ý wanted to take a deeper look – to do so, they developed a statistical test in which they matched people with schizophrenia (“cases”) to people without the disease (“controls”) and compared these duplications and deletions (known as copy number variation, or CNV). Their work appeared in the journal earlier this month. Soumya answered our questions about his research at the ӳ����ý, his role as a physician, and his appearance in the 2009 annual report.

Q1: Other studies have suggested that genetic variants in brain genes dramatically increase the risk of schizophrenia, but your study suggests that effect is much more modest. What accounts for this difference?

Soumya: The issue is that genes that are involved in brain function tend to be very, very large compared to other genes. In fact, if you look at genes in the genome that are larger than one megabase, almost all of them are in one shape or form involved in brain function. Consequently, if you look at duplication and deletion events without carefully taking gene size into account, it’s more likely than not that you’ll hit some genes with brain function, just because they are large genes.

Q2: What makes this paper different than previous papers on schizophrenia?

Soumya: This paper is really different from previous papers in terms of its analytical approach. We developed a rigorous statistical approach to conclusively show whether or not events that overlap with genes in a particular pathway such as genes involved in brain function increase your risk of disease. We didn’t actually answer the question of whether or not deletions or duplications in genes with brain function increase your risk of psychiatric disease, but we provided a path to get at that and with large enough sample collections, researchers should be able to address this issue. Our study does clearly show that the effect of having a CNV overlapping a brain function gene on schizophrenia risk for an individual is much more modest than previously suggested.

Q3: Is it unusual for you to work on a project related to schizophrenia? What is your usual area of focus?

Soumya: Much of the work that I do is trying to understand the genetics of autoimmune diseases but what I’m most interested in is trying to take what we learn from the genetics of autoimmune disease and connect that to mechanisms that cause other diseases. That’s gotten me interested in the broad question of looking at genetic variants and trying to see if there are common pathways that are impacted. That was how I got interested in this particular issue in schizophrenia. While the particular disease is different, a lot of the methods and the thinking in terms of trying to connect particular genetic variants to specific pathways are very similar.

Q4: Do you currently see patients? How do you balance the demands of the clinic with your role as a researcher?

Soumya: I currently have a full panel of patients in the rheumatology clinic at Brigham and Women’s Hospital. I enjoy seeing patients and being a doctor tremendously and I enjoy being active at the ӳ����ý and doing genomics and genetics research just as much. The two roles inform each other in interesting ways. Being able to see patients in the clinic gives you a sense of what genomics and genetics might be able to contribute and what they might not be able to contribute. Having a sense of the realistic features of clinical medicine, and having a sense of the art as much as the science of medicine has helped me have some perspective as we move into this era of personalized genomic medicine.

Q5: You have a stunning photo in last year’s annual report (page 19). What was it like working with a photographer to tell the story of your research visually?

Soumya: Working with was a lot of fun. My father is a former Kodak employee and has been an amateur photographer for most of his life so I was the subject of lots of photos growing up, but absolutely nothing like this. When you write a paper, one of the greatest challenges is trying to come up with that one-sentence title or that five-sentence abstract that encapsulates everything else that’s going on in the paper, and I thought that this was a similar exercise. You’re trying to come up with an image that captures what you do and what your relationship is to the ӳ����ý and where you’re coming from in a single image. It was a lot of fun and Len is just a tremendously talented photographer. I really enjoyed working with him.

Soumya Raychaudhuri recently completed his postdoctoral fellowship at the ӳ����ý within the Medical and Population Genetics group. He is a newly hired faculty member within the Divisions of Genetics and Rheumatology at Brigham and Women’s Hospital and Harvard Medical School. His research centers on the genetic pathways (or interactions between groups of genes) that lead to human diseases, especially autoimmune diseases. Soumya has become increasingly interested in how CNVs affect these pathways. In addition to studying autoimmune diseases like rheumatoid arthritis, Soumya has worked with ӳ����ý senior associate member Matthew Meyerson’s cancer group to look at CNVs in the cancer genome.