umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Modeling prior information of common genetic variants improves gene discovery for neuroticism
Umeå University, Faculty of Medicine, Department of Radiation Sciences. Department of Radiology, Center for Multimodal Imaging and Genetics, University of California, San Diego, La Jolla, CA 92037, USA.
Show others and affiliations
2017 (English)In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 26, no 22, p. 4530-4539Article in journal (Refereed) Published
Abstract [en]

Neuroticism reflects emotional instability, and is related to various mental and physical health issues. However, the majority of genetic variants associated with neuroticism remain unclear. Inconsistent genetic variants identified by different genome-wide association studies (GWAS) may be attributable to low statistical power. We proposed a novel framework to improve the power for gene discovery by incorporating prior information of single nucleotide polymorphisms (SNPs) and combining two relevant existing tools, relative enrichment score (RES) and conditional false discovery rate (FDR). Here, SNP's conditional FDR was estimated given its RES based on SNP prior information including linkage disequilibrium (LD)-weighted genic annotation scores, total LD scores and heterozygosity. A known significant locus in chromosome 8p was excluded before estimating FDR due to long-range LD structure. Only one significant LD-independent SNP was detected by analyses of unconditional FDR and traditional GWAS in the discovery sample (N = 59 225), and notably four additional SNPs by conditional FDR. Three of the five SNPs, all identified by conditional FDR, were replicated (P < 0.05) in an independent sample (N = 170 911). These three SNPs are located in intronic regions of CADM2, LINGO2 and EP300 which have been reported to be associated with autism, Parkinson's disease and schizophrenia, respectively. Our approach using a combination of RES and conditional FDR improved power of traditional GWAS for gene discovery providing a useful framework for the analysis of GWAS summary statistics by utilizing SNP prior information, and helping to elucidate the links between neuroticism and complex diseases from a genetic perspective.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS , 2017. Vol. 26, no 22, p. 4530-4539
National Category
Medical Genetics
Identifiers
URN: urn:nbn:se:umu:diva-142238DOI: 10.1093/hmg/ddx340ISI: 000414403900019OAI: oai:DiVA.org:umu-142238DiVA, id: diva2:1164670
Available from: 2017-12-11 Created: 2017-12-11 Last updated: 2018-06-09Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full text

Authority records BETA

Kauppi, Karolina

Search in DiVA

By author/editor
Kauppi, Karolina
By organisation
Department of Radiation Sciences
In the same journal
Human Molecular Genetics
Medical Genetics

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 47 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf