Premium
Searching genetic risk factors for schizophrenia and bipolar disorder: learn from the past and back to the future
Author(s) -
Alaerts Maaike,
DelFavero Jurgen
Publication year - 2009
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21042
Subject(s) - genome wide association study , genetic association , biology , hum , copy number variation , bipolar disorder , locus (genetics) , genetics , candidate gene , schizophrenia (object oriented programming) , linkage (software) , allele , single nucleotide polymorphism , gene , psychology , psychiatry , genome , genotype , neuroscience , cognition , art , performance art , art history
For more than 20 years already, researchers from all over the world have tried to get insight into the genetic basis of psychiatric disorders such as schizophrenia (SZ) and bipolar (BP) disorder. Linkage and candidate gene association study results have led to a range of hypotheses about the pathogenesis of the disorders, but overall genetic findings have been inconsistent and not a single functional risk causing variant has yet been identified. Even genomewide association (GWA) studies in large samples, the most extensive and systematic interrogation of the genome thus far, seemingly have not brought the expected answers. A reasonable interpretation is that multiple rare variants, inherently linked with locus and allelic heterogeneity, confer a substantial proportion of susceptibility to the disorders. Also, structural variation might be an important factor and promising results are arising from copy‐number variation (CNV) analyses. In this review we shortly touch on “old” results from linkage and association studies and critically review the design and “new” results of GWA and CNV studies. We discuss what can be learned from the past and how this knowledge can be used in future study designs. Hum Mutat 30, 1139–1152, 2009. © 2009 Wiley‐Liss, Inc.