title: Genome-wide association of bipolar disorder suggests an enrichment of replicable associations in regions near genes.
abstract: Although a highly heritable and disabling disease, bipolar disorder's (BD) genetic variants have been challenging to identify. We present new genotype data for 1,190 cases and 401 controls and perform a genome-wide association study including additional samples for a total of 2,191 cases and 1,434 controls. We do not detect genome-wide significant associations for individual loci; however, across all SNPs, we show an association between the power to detect effects calculated from a previous genome-wide association study and evidence for replication (P = 1.5×10(-7)). To demonstrate that this result is not likely to be a false positive, we analyze replication rates in a large meta-analysis of height and show that, in a large enough study, associations replicate as a function of power, approaching a linear relationship. Within BD, SNPs near exons exhibit a greater probability of replication, supporting an enrichment of reproducible associations near functional regions of genes. These results indicate that there is likely common genetic variation associated with BD near exons (±10 kb) that could be identified in larger studies and, further, provide a framework for assessing the potential for replication when combining results from multiple studies.
authors: Scripps Genomic Medicine and Scripps Translational Science Institute, La Jolla, California, United States of America.
authors: Erin N
authors: EN
authors: Smith
authors: Daniel L
authors: DL
authors: Koller
authors: Corrie
authors: C
authors: Panganiban
authors: Szabolcs
authors: S
authors: Szelinger
authors: Peng
authors: P
authors: Zhang
authors: Judith A
authors: JA
authors: Badner
authors: Thomas B
authors: TB
authors: Barrett
authors: Wade H
authors: WH
authors: Berrettini
authors: Cinnamon S
authors: CS
authors: Bloss
authors: William
authors: W
authors: Byerley
authors: William
authors: W
authors: Coryell
authors: Howard J
authors: HJ
authors: Edenberg
authors: Tatiana
authors: T
authors: Foroud
authors: Elliot S
authors: ES
authors: Gershon
authors: Tiffany A
authors: TA
authors: Greenwood
authors: Yiran
authors: Y
authors: Guo
authors: Maria
authors: M
authors: Hipolito
authors: Brendan J
authors: BJ
authors: Keating
authors: William B
authors: WB
authors: Lawson
authors: Chunyu
authors: C
authors: Liu
authors: Pamela B
authors: PB
authors: Mahon
authors: Melvin G
authors: MG
authors: McInnis
authors: Francis J
authors: FJ
authors: McMahon
authors: Rebecca
authors: R
authors: McKinney
authors: Sarah S
authors: SS
authors: Murray
authors: Caroline M
authors: CM
authors: Nievergelt
authors: John I
authors: JI
authors: Nurnberger
authors: Evaristus A
authors: EA
authors: Nwulia
authors: James B
authors: JB
authors: Potash
authors: John
authors: J
authors: Rice
authors: Thomas G
authors: TG
authors: Schulze
authors: William A
authors: WA
authors: Scheftner
authors: Paul D
authors: PD
authors: Shilling
authors: Peter P
authors: PP
authors: Zandi
authors: Sebastian
authors: S
authors: Zöllner
authors: David W
authors: DW
authors: Craig
authors: Nicholas J
authors: NJ
authors: Schork
authors: John R
authors: JR
authors: Kelsoe
mesh_terms: D001714:Bipolar Disorder / Q000235:genetics*; D019295:Computational Biology; D005091:Exons; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics