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S004-1

Genetics in Psychiatry: a Framework for Infrastructure, Phenotyping and
Analysis

Thomas G. Schulze

Chair WPA Section on Genetics, Germany

Background/Objective: Modern psychiatric genetics aims to investigate the genetic basis
underlying the variability of psychiatric phenotypes. The objective of this workshop is to provide a
brief introduction to methods used in this rapidly evolving field. Classical genetic studies (family,
twin and adoption studies) show that psychiatric disorders are, to variable extent, familial and
heritable.

Method: As a polygenic architecture seems to underlie most psychiatric disorders, particular
emphasis is placed on their association with common variants (SNPs) in so-called genetic association
studies. Hypothesis-driven candidate gene association studies prevailed in the literature up to 2006.
The ever decreasing cost of SNP array technology has propelled the use of hypothesis-free
genome-wide association studies (GWAS). These were met with variable success in psychiatry,
mostly limited by sample size. In most cases, a large part of the heritability demonstrated in twin
studies seemed to remain unexplained. Several novel methods to explore this ‘missing heritability’
have been recently introduced. Polygenic profile scoring methods investigate the cumulative
contribution of a polygenic component involving thousands of common SNPs of very small effect.

Result: Moreover, Genome-wide Complex Trait Analysis (GCTA) methods have enabled the
estimation of the proportion of phenotypic variance attributed to common variants, so called
SNP-heritability, which represents an upper bound on GWAS-explained heritability.

Conclusion: Finally, both of these methods provide a means to explore pleiotropy (common genes
underlying various phenotypes), i.e. the cross-phenotype genetic correlations among various
psychiatric disorders or between psychiatric disorders and other medical conditions.