Genome-wide association study of recurrent early-onset major depressive disorder
| Autor: | K Neimanas, Daniel B. Mirel, James A. Knowles, Jianxin Shi, A Zvinyatskovskiy, Dubravka Jancic, Peter Holmans, William Lawson, J. K. Johnson, James B. Potash, Ranjana Verma, Nancy Hale, Pablo V. Gejman, Douglas F. Levinson, William Coryell, M Gladis, Myrna M. Weissman, N Ertman, J. R. DePaulo, William A. Scheftner, M Goodell, Oleg V. Evgrafov, S Chaudhury, Alan R. Sanders, N Ney, Philip Adams |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Genotype Sp4 Transcription Factor Genome-wide association study Single-nucleotide polymorphism Biology Logistic regression Polymorphism Single Nucleotide Article neuroscience 03 medical and health sciences Cellular and Molecular Neuroscience Sex Factors 0302 clinical medicine Gene Frequency Recurrence medicine Humans GWAS Genetic Predisposition to Disease genetics International HapMap Project Molecular Biology X chromosome Aged 030304 developmental biology Genetics Depressive Disorder Major 0303 health sciences major depressive disorder Chromosome Mapping Middle Aged Microarray Analysis medicine.disease Europe Minor allele frequency Psychiatry and Mental health Logistic Models Major depressive disorder Female 030217 neurology & neurosurgery Genome-Wide Association Study |
| Zdroj: | Molecular psychiatry |
| ISSN: | 1476-5578 1359-4184 1707-7540 |
| DOI: | 10.1038/mp.2009.124 |
| Popis: | 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 P5 × 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. |
| Databáze: | OpenAIRE |
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