Genome-wide association study of recurrent early-onset major depressive disorder

J. Shi, James Bennett Potash, J. A. Knowles, M. M. Weissman, W. Coryell, W. A. Scheftner, W. B. Lawson, J Raymond Depaulo, P. V. Gejman, A. R. Sanders, J. K. Johnson, P. Adams, S. Chaudhury, D. Jancic, O. Evgrafov, A. Zvinyatskovskiy, N. Ertman, M. Gladis, K. Neimanas, M. Goodell & 6 others N. Hale, N. Ney, R. Verma, D. Mirel, P. Holmans, D. F. Levinson

Research output: Contribution to journalArticle

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 P5 × 10 -8 approximates a 5% genome-wide significance threshold. The strongest evidence for association was observed on chromosome 18q22.1 (rs17077540, P1.83 × 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.

Original languageEnglish (US)
Pages (from-to)193-201
Number of pages9
JournalMolecular Psychiatry
Volume16
Issue number2
DOIs
StatePublished - Feb 2011

Fingerprint

Genome-Wide Association Study
Major Depressive Disorder
Single Nucleotide Polymorphism
Genome
Meta-Analysis
HapMap Project
Brain
X Chromosome
Age of Onset
Gene Frequency
Quality Control
Transcription Factors
Chromosomes
Logistic Models
Messenger RNA

Keywords

  • genetics
  • genotype
  • GWAS
  • major depressive disorder
  • neuroscience

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Shi, J., Potash, J. B., Knowles, J. A., Weissman, M. M., Coryell, W., Scheftner, W. A., ... Levinson, D. F. (2011). Genome-wide association study of recurrent early-onset major depressive disorder. Molecular Psychiatry, 16(2), 193-201. https://doi.org/10.1038/mp.2009.124

Genome-wide association study of recurrent early-onset major depressive disorder. / Shi, J.; Potash, James Bennett; Knowles, J. A.; Weissman, M. M.; Coryell, W.; Scheftner, W. A.; Lawson, W. B.; Depaulo, J Raymond; Gejman, P. V.; Sanders, A. R.; Johnson, J. K.; Adams, P.; Chaudhury, S.; Jancic, D.; Evgrafov, O.; Zvinyatskovskiy, A.; Ertman, N.; Gladis, M.; Neimanas, K.; Goodell, M.; Hale, N.; Ney, N.; Verma, R.; Mirel, D.; Holmans, P.; Levinson, D. F.

In: Molecular Psychiatry, Vol. 16, No. 2, 02.2011, p. 193-201.

Research output: Contribution to journalArticle

Shi, J, Potash, JB, Knowles, JA, Weissman, MM, Coryell, W, Scheftner, WA, Lawson, WB, Depaulo, JR, Gejman, PV, Sanders, AR, Johnson, JK, Adams, P, Chaudhury, S, Jancic, D, Evgrafov, O, Zvinyatskovskiy, A, Ertman, N, Gladis, M, Neimanas, K, Goodell, M, Hale, N, Ney, N, Verma, R, Mirel, D, Holmans, P & Levinson, DF 2011, 'Genome-wide association study of recurrent early-onset major depressive disorder', Molecular Psychiatry, vol. 16, no. 2, pp. 193-201. https://doi.org/10.1038/mp.2009.124
Shi J, Potash JB, Knowles JA, Weissman MM, Coryell W, Scheftner WA et al. Genome-wide association study of recurrent early-onset major depressive disorder. Molecular Psychiatry. 2011 Feb;16(2):193-201. https://doi.org/10.1038/mp.2009.124
Shi, J. ; Potash, James Bennett ; Knowles, J. A. ; Weissman, M. M. ; Coryell, W. ; Scheftner, W. A. ; Lawson, W. B. ; Depaulo, J Raymond ; Gejman, P. V. ; Sanders, A. R. ; Johnson, J. K. ; Adams, P. ; Chaudhury, S. ; Jancic, D. ; Evgrafov, O. ; Zvinyatskovskiy, A. ; Ertman, N. ; Gladis, M. ; Neimanas, K. ; Goodell, M. ; Hale, N. ; Ney, N. ; Verma, R. ; Mirel, D. ; Holmans, P. ; Levinson, D. F. / Genome-wide association study of recurrent early-onset major depressive disorder. In: Molecular Psychiatry. 2011 ; Vol. 16, No. 2. pp. 193-201.
@article{c302a59f2ea74ae5ac00a0ee2a50924c,
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 P5 × 10 -8 approximates a 5{\%} genome-wide significance threshold. The strongest evidence for association was observed on chromosome 18q22.1 (rs17077540, P1.83 × 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.",
keywords = "genetics, genotype, GWAS, major depressive disorder, neuroscience",
author = "J. Shi and Potash, {James Bennett} and Knowles, {J. A.} and Weissman, {M. M.} and W. Coryell and Scheftner, {W. A.} and Lawson, {W. B.} and Depaulo, {J Raymond} and Gejman, {P. V.} and Sanders, {A. R.} and Johnson, {J. K.} and P. Adams and S. Chaudhury and D. Jancic and O. Evgrafov and A. Zvinyatskovskiy and N. Ertman and M. Gladis and K. Neimanas and M. Goodell and N. Hale and N. Ney and R. Verma and D. Mirel and P. Holmans and Levinson, {D. F.}",
year = "2011",
month = "2",
doi = "10.1038/mp.2009.124",
language = "English (US)",
volume = "16",
pages = "193--201",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - Genome-wide association study of recurrent early-onset major depressive disorder

AU - Shi, J.

AU - Potash, James Bennett

AU - Knowles, J. A.

AU - Weissman, M. M.

AU - Coryell, W.

AU - Scheftner, W. A.

AU - Lawson, W. B.

AU - Depaulo, J Raymond

AU - Gejman, P. V.

AU - Sanders, A. R.

AU - Johnson, J. K.

AU - Adams, P.

AU - Chaudhury, S.

AU - Jancic, D.

AU - Evgrafov, O.

AU - Zvinyatskovskiy, A.

AU - Ertman, N.

AU - Gladis, M.

AU - Neimanas, K.

AU - Goodell, M.

AU - Hale, N.

AU - Ney, N.

AU - Verma, R.

AU - Mirel, D.

AU - Holmans, P.

AU - Levinson, D. F.

PY - 2011/2

Y1 - 2011/2

N2 - 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, P1.83 × 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.

AB - 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, P1.83 × 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.

KW - genetics

KW - genotype

KW - GWAS

KW - major depressive disorder

KW - neuroscience

UR - http://www.scopus.com/inward/record.url?scp=79151477241&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79151477241&partnerID=8YFLogxK

U2 - 10.1038/mp.2009.124

DO - 10.1038/mp.2009.124

M3 - Article

VL - 16

SP - 193

EP - 201

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

IS - 2

ER -