Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2013 Oct 30;80(3):578-87.
doi: 10.1016/j.neuron.2013.10.046.

Progress in the Genetics of Polygenic Brain Disorders: Significant New Challenges for Neurobiology

Affiliations
Free PMC article
Review

Progress in the Genetics of Polygenic Brain Disorders: Significant New Challenges for Neurobiology

Steven A McCarroll et al. Neuron. .
Free PMC article

Abstract

Advances in genome analysis, accompanied by the assembly of large patient cohorts, are making possible successful genetic analyses of polygenic brain disorders. If the resulting molecular clues, previously hidden in the genomes of affected individuals, are to yield useful information about pathogenesis and inform the discovery of new treatments, neurobiology will have to rise to many difficult challenges. Here we review the underlying logic of the genetic investigations, describe in more detail progress in schizophrenia and autism, and outline the challenges for neurobiology that lie ahead. We argue that technologies at the disposal of neuroscience are adequately advanced to begin to study the biology of common and devastating polygenic disorders.

Figures

Figure 1
Figure 1
Different kinds of genetic variation and different approaches to genetic analysis are influenced by human population history. (a) Humans have an eccentric population history, in which small, ancestral populations rapidly expanded into a population of some seven billion individuals. (b) Genetic variants that have arisen recently in human history, including new mutations, are generally ascertained by genome sequencing. (c) Polymorphisms that were already present in the small, ancestral populations can be systematically evaluated for relationship to phenotypes, on thousands of genetic backgrounds, using inexpensive array-based assay platforms.
Figure 2
Figure 2
Emerging genetic evidence on complex brain disorders converges on specific molecular complexes. (a) Multiple subunits of voltage-gated calcium channels are among the genome's strongest associations to schizophrenia and bipolar disorder. (b) Genes encoding the postsynaptic components of excitatory synapses are implicated by both rare and common variants in schizophrenia.

Similar articles

See all similar articles

Cited by 30 articles

See all "Cited by" articles

Publication types

LinkOut - more resources

Feedback