title: Genome-wide association study of bipolar disorder in European American and African American individuals.
abstract: To identify bipolar disorder (BD) genetic susceptibility factors, we conducted two genome-wide association (GWA) studies: one involving a sample of individuals of European ancestry (EA; n=1001 cases; n=1033 controls), and one involving a sample of individuals of African ancestry (AA; n=345 cases; n=670 controls). For the EA sample, single-nucleotide polymorphisms (SNPs) with the strongest statistical evidence for association included rs5907577 in an intergenic region at Xq27.1 (P=1.6 x 10(-6)) and rs10193871 in NAP5 at 2q21.2 (P=9.8 x 10(-6)). For the AA sample, SNPs with the strongest statistical evidence for association included rs2111504 in DPY19L3 at 19q13.11 (P=1.5 x 10(-6)) and rs2769605 in NTRK2 at 9q21.33 (P=4.5 x 10(-5)). We also investigated whether we could provide support for three regions previously associated with BD, and we showed that the ANK3 region replicates in our sample, along with some support for C15Orf53; other evidence implicates BD candidate genes such as SLITRK2. We also tested the hypothesis that BD susceptibility variants exhibit genetic background-dependent effects. SNPs with the strongest statistical evidence for genetic background effects included rs11208285 in ROR1 at 1p31.3 (P=1.4 x 10(-6)), rs4657247 in RGS5 at 1q23.3 (P=4.1 x 10(-6)), and rs7078071 in BTBD16 at 10q26.13 (P=4.5 x 10(-6)). This study is the first to conduct GWA of BD in individuals of AA and suggests that genetic variations that contribute to BD may vary as a function of ancestry.
authors.affiliation: Scripps Genomic Medicine, Scripps Translational Science Institute, La Jolla, CA, USA.
authors.forename: E N
authors.initials: EN
authors.lastname: Smith
authors.forename: C S
authors.initials: CS
authors.lastname: Bloss
authors.forename: J A
authors.initials: JA
authors.lastname: Badner
authors.forename: T
authors.initials: T
authors.lastname: Barrett
authors.forename: P L
authors.initials: PL
authors.lastname: Belmonte
authors.forename: W
authors.initials: W
authors.lastname: Berrettini
authors.forename: W
authors.initials: W
authors.lastname: Byerley
authors.forename: W
authors.initials: W
authors.lastname: Coryell
authors.forename: D
authors.initials: D
authors.lastname: Craig
authors.forename: H J
authors.initials: HJ
authors.lastname: Edenberg
authors.forename: E
authors.initials: E
authors.lastname: Eskin
authors.forename: T
authors.initials: T
authors.lastname: Foroud
authors.forename: E
authors.initials: E
authors.lastname: Gershon
authors.forename: T A
authors.initials: TA
authors.lastname: Greenwood
authors.forename: M
authors.initials: M
authors.lastname: Hipolito
authors.forename: D L
authors.initials: DL
authors.lastname: Koller
authors.forename: W B
authors.initials: WB
authors.lastname: Lawson
authors.forename: C
authors.initials: C
authors.lastname: Liu
authors.forename: F
authors.initials: F
authors.lastname: Lohoff
authors.forename: M G
authors.initials: MG
authors.lastname: McInnis
authors.forename: F J
authors.initials: FJ
authors.lastname: McMahon
authors.forename: D B
authors.initials: DB
authors.lastname: Mirel
authors.forename: S S
authors.initials: SS
authors.lastname: Murray
authors.forename: C
authors.initials: C
authors.lastname: Nievergelt
authors.forename: J
authors.initials: J
authors.lastname: Nurnberger
authors.forename: E A
authors.initials: EA
authors.lastname: Nwulia
authors.forename: J
authors.initials: J
authors.lastname: Paschall
authors.forename: J B
authors.initials: JB
authors.lastname: Potash
authors.forename: J
authors.initials: J
authors.lastname: Rice
authors.forename: T G
authors.initials: TG
authors.lastname: Schulze
authors.forename: W
authors.initials: W
authors.lastname: Scheftner
authors.forename: C
authors.initials: C
authors.lastname: Panganiban
authors.forename: N
authors.initials: N
authors.lastname: Zaitlen
authors.forename: P P
authors.initials: PP
authors.lastname: Zandi
authors.forename: S
authors.initials: S
authors.lastname: Zöllner
authors.forename: N J
authors.initials: NJ
authors.lastname: Schork
authors.forename: J R
authors.initials: JR
authors.lastname: Kelsoe
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D001714:Bipolar Disorder / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D044465:White People; D055815:Young Adult