title: Genome-wide association study of recurrent early-onset major depressive disorder.
abstract: A genome-wide association study was carried out in 1020 case subjects with recurrent early-onset major depressive disorder (MDD) (onset before age 31) and 1636 control subjects screened to exclude lifetime MDD. Subjects were genotyped with the Affymetrix 6.0 platform. After extensive quality control procedures, 671 424 autosomal single nucleotide polymorphisms (SNPs) and 25 068 X chromosome SNPs with minor allele frequency greater than 1% were available for analysis. An additional 1 892 186 HapMap II SNPs were analyzed based on imputed genotypic data. Single-SNP logistic regression trend tests were computed, with correction for ancestry-informative principal component scores. No genome-wide significant evidence for association was observed, assuming that nominal P<5 × 10(-8) approximates a 5% genome-wide significance threshold. The strongest evidence for association was observed on chromosome 18q22.1 (rs17077540, P=1.83 × 10(-7)) in a region that has produced some evidence for linkage to bipolar-I or -II disorder in several studies, within an mRNA detected in human brain tissue (BC053410) and approximately 75 kb upstream of DSEL. Comparing these results with those of a meta-analysis of three MDD GWAS data sets reported in a companion article, we note that among the strongest signals observed in the GenRED sample, the meta-analysis provided the greatest support (although not at a genome-wide significant level) for association of MDD to SNPs within SP4, a brain-specific transcription factor. Larger samples will be required to confirm the hypothesis of association between MDD (and particularly the recurrent early-onset subtype) and common SNPs.
authors.affiliation: Department of Psychiatry, Stanford University, Stanford, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Shi
authors.forename: J B
authors.initials: JB
authors.lastname: Potash
authors.forename: J A
authors.initials: JA
authors.lastname: Knowles
authors.forename: M M
authors.initials: MM
authors.lastname: Weissman
authors.forename: W
authors.initials: W
authors.lastname: Coryell
authors.forename: W A
authors.initials: WA
authors.lastname: Scheftner
authors.forename: W B
authors.initials: WB
authors.lastname: Lawson
authors.forename: J R
authors.initials: JR
authors.lastname: DePaulo
authors.forename: P V
authors.initials: PV
authors.lastname: Gejman
authors.forename: A R
authors.initials: AR
authors.lastname: Sanders
authors.forename: J K
authors.initials: JK
authors.lastname: Johnson
authors.forename: P
authors.initials: P
authors.lastname: Adams
authors.forename: S
authors.initials: S
authors.lastname: Chaudhury
authors.forename: D
authors.initials: D
authors.lastname: Jancic
authors.forename: O
authors.initials: O
authors.lastname: Evgrafov
authors.forename: A
authors.initials: A
authors.lastname: Zvinyatskovskiy
authors.forename: N
authors.initials: N
authors.lastname: Ertman
authors.forename: M
authors.initials: M
authors.lastname: Gladis
authors.forename: K
authors.initials: K
authors.lastname: Neimanas
authors.forename: M
authors.initials: M
authors.lastname: Goodell
authors.forename: N
authors.initials: N
authors.lastname: Hale
authors.forename: N
authors.initials: N
authors.lastname: Ney
authors.forename: R
authors.initials: R
authors.lastname: Verma
authors.forename: D
authors.initials: D
authors.lastname: Mirel
authors.forename: P
authors.initials: P
authors.lastname: Holmans
authors.forename: D F
authors.initials: DF
authors.lastname: Levinson
mesh_terms: D000328:Adult; D000368:Aged; D002874:Chromosome Mapping; D003865:Major Depressive Disorder / Q000235:genetics*; D005060:Europe; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D046228:Microarray Analysis / Q000379:methods; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012008:Recurrence; D012737:Sex Factors; D051706:Sp4 Transcription Factor / Q000235:genetics
chemical_list: C497124:SP4 protein, human; D051706:Sp4 Transcription Factor