Research Review: Polygenic methods and their application to psychiatric traits

Wray, Naomi R., Lee, Sang Hong, Mehta, Divya, Vinkhuyzen, Anna A. E., Dudbridge, Frank and Middeldorp, Christel M. (2014) Research Review: Polygenic methods and their application to psychiatric traits. Journal of Child Psychology and Psychiatry, 55 10: 1068-1087. doi:10.1111/jcpp.12295

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
UQ342517_OA.pdf Full text (open access) application/pdf 1.52MB 64

Author Wray, Naomi R.
Lee, Sang Hong
Mehta, Divya
Vinkhuyzen, Anna A. E.
Dudbridge, Frank
Middeldorp, Christel M.
Title Research Review: Polygenic methods and their application to psychiatric traits
Journal name Journal of Child Psychology and Psychiatry   Check publisher's open access policy
ISSN 0021-9630
Publication date 2014
Year available 2014
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1111/jcpp.12295
Open Access Status File (Author Post-print)
Volume 55
Issue 10
Start page 1068
End page 1087
Total pages 20
Place of publication Malden, MA United States
Publisher Blackwell Publishing
Collection year 2015
Language eng
Abstract Despite evidence from twin and family studies for an important contribution of genetic factors to both childhood and adult onset psychiatric disorders, identifying robustly associated specific DNA variants has proved challenging. In the pregenomics era the genetic architecture (number, frequency and effect size of risk variants) of complex genetic disorders was unknown. Empirical evidence for the genetic architecture of psychiatric disorders is emerging from the genetic studies of the last 5 years. Methods and scope: We review the methods investigating the polygenic nature of complex disorders. We provide mini-guides to genomic profile (or polygenic) risk scoring and to estimation of variance (or heritability) from common SNPs; a glossary of key terms is also provided. We review results of applications of the methods to psychiatric disorders and related traits and consider how these methods inform on missing heritability, hidden heritability and still-missing heritability. Findings: Genome-wide genotyping and sequencing studies are providing evidence that psychiatric disorders are truly polygenic, that is they have a genetic architecture of many genetic variants, including risk variants that are both common and rare in the population. Sample sizes published to date are mostly underpowered to detect effect sizes of the magnitude presented by nature, and these effect sizes may be constrained by the biological validity of the diagnostic constructs. Conclusions: Increasing the sample size for genome wide association studies of psychiatric disorders will lead to the identification of more associated genetic variants, as already found for schizophrenia. These loci provide the starting point of functional analyses that might eventually lead to new prevention and treatment options and to improved biological validity of diagnostic constructs. Polygenic analyses will contribute further to our understanding of complex genetic traits as sample sizes increase and as sample resources become richer in phenotypic descriptors, both in terms of clinical symptoms and of nongenetic risk factors.
Keyword Disease traits
Genome wide association studies
Polygenic risk scoring
Psychiatric disorders
SNP analyses
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Queensland Brain Institute Publications
Official 2015 Collection
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 40 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 43 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 21 Oct 2014, 00:51:32 EST by System User on behalf of Queensland Brain Institute