Etiology of Psychiatric and Behavioral Disorders
Etiology of Psychiatric Disorders
The major focus of the Sullivan lab is the genetic dissection of complex traits of great public health importance — particularly schizophrenia, major depressive disorder (including post-partum depression), eating disorders, and autism. The goal is to investigate the etiology, pharmacogenetics, and clinical heterogeneity of these disorders.
We take the phrase "complex trait" seriously; no single lab will be able to solve these problems in isolation. This requires that we collaborate in a real way with experts in many other disciplines. We have deep links with researchers in other UNC departments/centers and other institutions worldwide. These collaborations form the core of our Center for Psychiatric Genomics, a highly efficient “virtual laboratory” that brings together leaders in relevant fields from around the world.
The Psychiatric Genomics Consortium
The purpose of the PGC is to conduct mega-analyses of genome-wide genetic data for psychiatric disorders. The central goal of psychiatric genetics is to discover loci that are robustly and repeatedly associated with a disorder and thereby gain insight into causation. The basic idea behind the PGC is that individual studies are too small to identify robust and replicable associations. Meta-analysis is a widely-used technique that can combine information across studies. We use “mega-analysis” because all of our analyses are based on individual genotype data.
Dr Sullivan is a one of the founders and the lead PI of the PGC. The PGC began in early 2007, and quickly became a confederation of most investigators in the field. The PGC has 500+ investigators from 80+ institutions in 25 countries. There are 170,000+ subjects currently in analysis, and this number is growing rapidly. Thus, the PGC is the largest consortium and the largest biological experiment in the history of psychiatry.
The PGC is passionate about open, inclusive, participatory, and democratic science. Given the importance of the problems we study, we are committed to rapid progress. From 2007-11, the PGC focused on autism, attention-deficit hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia. We now include large studies of anorexia nervosa, drug use disorders, OCD/Tourette's, and PTSD. Initially, the PGC focused on common SNPs. Our focus has expanded to include copy number variation and uncommon/rare genetic variation.The PGC has received funding from many sources. The PGC has relied heavily on the goodwill of its members and their donated effort. Establishing and genotyping the primary studies were funded by a wide range of national, international, and commercial funders.
This is a chronic and debilitating mental disorder that affects approximately 1% of the human population. It is clear that genetics plays a role in schizophrenia, and our group has played a major role in identifying >130 specific genomic loci that have a causal role in the disease. The Sullivan lab is conducting a series of studies to begin to elucidate the etiology of schizophrenia, beginning with these associated genes. In addition, pharmacogenetic studies are underway to determine the mechanism of action of antipsychotic drugs that are currently used to treat some of the symptoms of schizophrenia.
We participate in genomic searches of multiple types including rare exonic variation, rare copy number variation, and common variation using genome-wide association studies (GWAS). GWAS examine many common genetic variants in different individuals to see if any variant is associated with a disease like schizophrenia. The Sullivan lab has utilized the GWAS approach to identify genomic loci associated with schizophrenia and a wide range of psychiatric disorders (e.g. major depressive disorder and anorexia nervosa) and pharmacogenetic traits.
Sullivan PF, Keefe RS, Lange LA, Lange EM, Stroup TS, Lieberman J, Maness PF. (2007) NCAM1 and Neurocognition in Schizophrenia. Biol Psychiatry. 61(7):902-10.
Furberg H, Lichtenstein P, Pedersen NL, Bulik C, Sullivan PF. (2006) Cigarettes and oral snuff use in Sweden: Prevalence and transitions. Addiction. 101(10):1509-15.
Sullivan PF, Montgomery GW, Hottenga JJ, Wray NR, Boomsma DI, Martin NG. (2006) Empirical evaluation of the genetic similarity of samples from twin registries in Australia and the Netherlands using 359 STRP markers. Twin Res Hum Genet. 9(4):600-2.
Lichtenstein P, Bjork C, Hultman CM, Scolnick E, Sklar P, Sullivan PF. (2006) Recurrence risks for schizophrenia in a Swedish national cohort. Psychol Med. 36(10):1417-25.
Forlenza MJ, Hall P, Lichtenstein P, Evengard B, Sullivan PF. (2005) Epidemiology of cancer-related fatigue in the Swedish twin registry. Cancer 104:2022-203.
Sullivan PF. (2005) The genetics of schizophrenia. PLoS Med. 2(7):e212.
Sullivan PF, Neale BM, van den Oord E, Miles MF, Neale MC, Bulik CM, Joyce PR, Straub RE, Kendler KS. (2004) Candidate genes for nicotine dependence via linkage, epistasis, and bioinformatics. Am J Med Genet B Neuropsychiatr Genet 126:23-36