Schizophrenia by David Anthony S. Kapur Shitij McGuffin Peter

Author:David, Anthony S., Kapur, Shitij, McGuffin, Peter
Language: eng
Format: epub
Publisher: Taylor & Francis

New directions: Molecular Genetics and Gene–Environment Interplay

In 1981 I moved to the United States to complete part of my MRC fellowship, as planned, at Washington University, St Louis. Some months later, Hugh Gurling made his journey to Stanford University to complete the overseas part his Wellcome Trust Fellowship. To each of us remarkable things happened. Gurling, who had previously been doing a twin study, became engrossed in molecular genetics whereas I, until then a dyed-in-the-wool genetic markers researcher, became entranced with quantitative genetics, which was all round me at “Wash U”. Washington University had now recruited Irv Gottesman to add to their array of quantitative talent in the psychiatry department and there were regular joint seminars with the Mathematics Department and the Biostatistics Department, headed by D. C. Rao. I had taken all of my linkage data from London with me and had been working through the analyses, as one did in those days, using pencil and paper, a hand-held calculator and a set of tables. I also had help and advice from Brian Suarez, who was the linkage expert at Wash U and whose papers I had studied while I was still in London. Suarez introduced me to the LIPED program written in FORTRAN by Jurg Ott. I had heard about LIPED and had had some discussions about using it, or her own FORTRAN programme, with Elizabeth Sturt, a statistician who worked in the MRC Social Psychiatry Unit at the Institute of Psychiatry. However now was a chance to actually apply LIPED, as far as I knew for the first time, on a psychiatric data set.

My data (McGuffin, Festenstein, & Murray, 1983) consisted entirely of what are now called “classical markers”, HLA and blood types and various protein polymorphisms that could be measured in peripheral blood. But now the “New Genetics” (Comings, 1980) of DNA markers was suddenly upon us. These consisted of potentially hundreds of restriction fragment length polymorphisms (RFLPs) that would enable an entire linkage map spanning the human genome to be produced with 100% coverage (as opposed to the few percent coverage achieved in a study such as mine). While I was dallying with stats, Gurling saw the real potential of the New Genetics for psychiatry and gained the training at Stanford that would enable him to exploit this on return to the UK.

With Robin Murray’s blessing and encouragement, on his return Hugh Gurling teamed up with Roger Marchbanks, a reader in the Neurochemistry Department, to set up molecular genetics in earnest at the Institute. I had returned to the UK at around the same time in the summer of 1982 and was subsequently awarded an MRC senior fellowship to carry out a study on the interplay between familial factors and psychosocial adversity in depression. This again followed on from a Murray suggestion and was a collaboration with Paul Bebbington and others in the MRC Social Psychiatry Unit. It involved, something fairly novel for me, no molecules at all. It did, however, help me to renew

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