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Opportunities and Risks of Personal Genomics Are Key Topics of Sunday’s Session of the World Congress of Psychiatric Genetics in Boston

Sunday’s (October 20) portion of the five-day 2013 XXIst World Congress of Psychiatric Genetics opened with a plenary session on the “Opportunities and Risks Associated with Personal & Clinical Genomics.” The format was a panel presentation chaired by Robert C. Green, M.D., M.P.H., Associate Professor of Medicine in the Division of Genetics at Brigham and Women’s Hospital and Harvard Medical School, Associate Director for Research at Partners Health Care for Personalized Genetic Medicine, and Director of Genes2People (GTP). The four distinguished panelists were Paul Appelbaum, M.D., Professor of Psychiatry, Medicine, & Law and Director of the Division of Law, Ethics, and Psychiatry in the Department of Psychiatry at Columbia University; Atul Butte, M.D., Ph.D., Chief of the Division of Systems Medicine and Associate Professor of Pediatrics, Medicine, and Computer Science at Stanford University and Lucile Packard Children's Hospital, and a co-founder of Personalis, a contract research organization and genome-scale diagnostics services company pioneering genome-guided medicine; A. Cecile Janssens, Ph.D., Professor at Emory University in Atlanta: and Uta Francke, M.D., Professor of Genetics and Pediatrics at Stanford School of Medicine, past President of the American Society of Human Genetics, and Senior Medical Director of the personal genomics company 23andMe. Dr. Green began by discussing the purposes of genetic testing: confirmation, diagnosis of mysterious diseases, risk profiling, and research. He also stressed context: medical versus consumer interest; clinical or research; pre-conception, pre-natal, pediatric or adult; various degrees of patient education; no results and anticipated results; and incidental findings. He mentioned two programs: Genomes2People and REVEAL that have grappled with problems of genetic disclosure. He also noted consumer-based companies such as 23andMe and Pathway Genomics that also struggle with such dilemmas. He reported that surveys have curiously shown that those who already know they have a particular disorder (e.g., bipolar disorder) tend to nevertheless be very interested in learning the results of their genetic tests, and that the degree of disease risk is not correlated with anxiety level. One goal of the clinical goals should be the production of an easily digestible, single-page summary report of the genetic results. He noted that clinical sequencing is already underway and is simply going to explode, bringing with it the enormous problem of how to handle incidental findings. He concluded by stressing that this is a rapidly moving field with many new developments occurring all the time. We have to realize that we will be “living on the edge of knowledge for a long time.” Dr. Butte kicked off the panelists’ presentations by saying that we will soon be paying more for parking than for sequencing and he contended that the price of sequencing is essentially irrelevant. His group has mined the data in over 19,000 papers and assembled a database (VARIMED) including 473,000 distinct SNPs. He argued that odds ratios should not be used, but rather should be replaced by likelihood ratios, which physicians are already trained in understanding. Dr. Butte closed by noting a radiologist typically analyzes 1 GB of data in 15 minutes when reviewing x-rays and scans, and that geneticists need better visualization tools to help them visualize traits. Dr. Francke, a world-class geneticist, spoke mainly from her perspective as Medical Director at 23andMe. She said that everyone has the right to know their personal genetics and that progress in this area has the potential to transform personalized medicine and that such progress can be accelerated by the accumulation and analysis of big data. She emphasized the simplicity of the 23andMe system which provides consumers with a kit which the consumer simply spits into and sends back to the company and the genotype is then returned to the consumer. She described the kit as being a 1 million SNP custom Illumina array that can detect 50 different carrier statuses, 121 health risks (GWAS-based), and 21 drug-response variations. Among the disease risks that are detected are adult onset MLD (ARSA-associated), bipolar disorder (Ank3-associated), restless legs syndrome (BTBBD9-associated), and Alzheimer’s disease (APOE-associated). Dr. Francke highlighted a recent Lancet study (2013) entitled “Identification of Risk Loci with Shared Effects on Five Major Psychiatric Disorders: A Genome-Wide Analysis.” The study particularly stressed the role of calcium-channel activity genes. Dr. Francke said that new discoveries are being made constantly and that big data (i.e., large datasets) are a key driver in this phenomenon. She then briefly discussed what people do with the genetic information they receive and while this varies, she said, the responses have been largely positive. Dr. Janssen began her talk by posing the question of how predictive is our DNA. She answered by saying that it runs the gamut from close to perfect, such as for Huntington’s disease, to hardly or not at all, such as for type 2 diabetes and multiple complex diseases. She then commented on the relative predictability of various diseases. High on her predictability scale were rare congenital disorders, inherited diseases, outbreaks and epidemics, and matching catches in forensics. At other end of the spectrum, in her opinion, were susceptibility to common disorders, pharmacogenomics, and nutrigenomics. She presented some interesting heritability figures with eye color at >99%, type 1 diabetes at 88%, schizophrenia at 81%, and type 2 diabetes at 26%. She argued that complex outcomes are simply too complex to predict, and drew analogies with cases of plane and boat crashes. She indicated that there is great opportunity for genetics to be useful in the diagnosis of rare diseases and outbreaks, and also in forensics. Opportunities in pharmacogenomics are less certain, while the outlook for common diseases is even bleaker, she said in closing. Dr. Appelbaum began by discussing the dilemma posed by incidental findings generated in these personal genome tests. He noted that surveys indicated subjects generally wanted to know their genetic results even when the data was bad. He posed the question of whether the discussion of test results should be outsourced to experts, as even researchers are generally not qualified to interpret results for subjects. At the end of Dr. Appelbaum’s talk, there was a lively interchange between the panel and the audience over this highly topical and controversial subject. After the plenary session came the presentation of awards. The coveted Snow and Ming Tsuang Lifetime Achievement Award was presented to John Nurnberger, Jr., M.D.,.Ph.D., Professor of Psychiatry at the Indiana University School of Medicine, who has been a leader in the development of tools to identify genes important in human behavior. Dr. Nurnberger was warmly introduced by an early mentor, Elliott Gershon, M.D., Professor of Psychiatry and Human Genetics at the University of Chicago. The Thomas Reich Young Investigator Award went to Stephan Ripke, M.D., a research scientist in the Analytical and Translational Genetics Unit at Massachusetts General Hospital (MGH) and a key member of the Psychiatric Genetics Consortium (PGC), which recently reported identifying over 100 schizophrenia-associated SNPs. The Richard Todd Award is given for an outstanding presentation in the category of childhood psychiatric disorders and went this year to Geert Poelmans, M.D., Ph.D., Founder and Director of Drug Target Identification and Development (DTID) for his poster entitled, “Whole-Genome mRNA Expression Profiling Reveals Disturbed Glutathione Signaling in a Rat Model of Schizophrenia.” Many other fascinating presentations were delivered throughout the day. The XXIst World Congress of Psychiatric Genetics will run through Monday, October 21, 2013. [The Lancet article] [World Congress of Psychiatric Genetics 2013] [by Michael D. O'Neill]