Danielle Posthuma, Vrije Universiteit (VU) Amsterdam

Complex Trait Genetics: From heritability to functional mechanisms

After decades of limited progress in identifying causal factors for mental disorders, the introduction of genome-wide association studies (GWAS) in 2005 revolutionized the field of psychiatric genetics. In GWAS, hundreds of thousands of genetic variants (single nucleotide polymorphisms or SNPs) are tested for association with disease in cohorts of cases and controls. Large-scale collaborative efforts have resulted in well-powered GWAS (with sample sizes up to 35,000 cases for mental disorders). Since 2007, these studies have yielded numerous robust and replicable genetic variants for several mental disorders. The largest collaborative effort ever in the history of medicine - the Psychiatric Genomics Consortium (PGC) - has now identified 128 independent common genetic variants for schizophrenia based on its current sample size of >82,000 subjects, as well as multiple rare variants for autism Some of these findings have led to novel biological hypotheses about mental disorders and have provided keys to potential treatments by revealing the unexpected involvement of biological functions and pathways in a variety of disease processes. After more than a century of limited progress, we now possess extraordinary new knowledge about the fundamental genetic architecture of mental disorders. The current challenges however are how to deal with the often polygenic nature of mental disorders and how to generate biological hypothesis that can be tested in functional experiments, and that will lead to increased insight into mechanistic disease processes. In this lecture an overview will be provided of the main developments in the field of human genetics, as well as its current challenges and an outlook to the future.

Organized by

John-Dylan Haynes