Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-2-25
pubmed:abstractText
Given the mounting convergent evidence implicating many more genes in complex disorders such as bipolar disorder than the small number identified unambiguously by the first-generation Genome-Wide Association studies (GWAS) to date, there is a strong need for improvements in methodology. One strategy is to include in the next generation GWAS larger numbers of subjects, and/or to pool independent studies into meta-analyses. We propose and provide proof of principle for the use of a complementary approach, convergent functional genomics (CFG), as a way of mining the existing GWAS datasets for signals that are there already, but did not reach significance using a genetics-only approach. With the CFG approach, the integration of genetics with genomics, of human and animal model data, and of multiple independent lines of evidence converging on the same genes offers a way of extracting signal from noise and prioritizing candidates. In essence our analysis is the most comprehensive integration of genetics and functional genomics to date in the field of bipolar disorder, yielding a series of novel (such as Klf12, Aldh1a1, A2bp1, Ak3l1, Rorb, Rora) and previously known (such as Bdnf, Arntl, Gsk3b, Disc1, Nrg1, Htr2a) candidate genes, blood biomarkers, as well as a comprehensive identification of pathways and mechanisms. These become prime targets for hypothesis driven follow-up studies, new drug development and personalized medicine approaches.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1552-485X
pubmed:author
pubmed:copyrightInfo
2008 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:day
5
pubmed:volume
150B
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
155-81
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Convergent functional genomics of genome-wide association data for bipolar disorder: comprehensive identification of candidate genes, pathways and mechanisms.
pubmed:affiliation
Department of Psychiatry, Indiana University School of Medicine, Indianapolis, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural