Evidence-based psychiatric genetics, AKA the false dichotomy between common and rare variant hypotheses.

摘要: In this article, we review some of the data that contribute to our understanding genetic architecture psychiatric disorders. These include results from evolutionary modelling (hence no data), observed recurrence risk relatives and molecular markers. We briefly discuss common-disease common-variant hypothesis, success (or otherwise) genome-wide association studies, evidence for polygenic variance likely exome whole-genome sequencing studies. conclude perceived dichotomy between ‘common’ ‘rare’ variants is not only false, but unhelpful in making progress towards increasing basis Strong has been accumulated consistent with contribution many genes disease, across a wide range allele frequencies substantial proportion variation population linkage disequilibrium single-nucleotide polymorphisms (SNPs) on commercial genotyping arrays. At same time, most causal segregate are be rare total these also explain significant variation. It combination frequency, effect size functional characteristics will determine new experimental paradigms such as whole exome/genome detect loci. Empirical suggest roughly half tagged by SNPs chips, individual have small size, average. larger sample sizes essential further biology underlying