Genome-wide association studies are a powerful tool for unravelling the genetic background of complex disorders such as major depression.We conducted a genome-wide association study of 604 patients with major depression and 1364 population based control subjects. The top hundred findings were followed up in a replication sample of 409 patients and 541 control subjects.Two SNPs showed nominally significant association in both the genome-wide association study and the replication samples: 1) rs9943849 (p(combined) = 3.24E-6) located upstream of the carboxypeptidase M (CPM) gene and 2) rs7713917 (p(combined) = 1.48E-6), located in a putative regulatory region of HOMER1. Further evidence for HOMER1 was obtained through gene-wide analysis while conditioning on the genotypes of rs7713917 (p(combined) = 4.12E-3). Homer1 knockout mice display behavioral traits that are paradigmatic of depression, and transcriptional variants of Homer1 result in the dysregulation of cortical-limbic circuitry. This is consistent with the findings of our subsequent human imaging genetics study, which revealed that variation in single nucleotide polymorphism rs7713917 had a significant influence on prefrontal activity during executive cognition and anticipation of reward.Our findings, combined with evidence from preclinical and animal studies, suggest that HOMER1 plays a role in the etiology of major depression and that the genetic variation affects depression via the dysregulation of cognitive and motivational processes.
Description
Genome-wide association-, replication-, and neuroimaging study implicates HOMER1 in the etiology of major depression. - PubMed - NCBI
%0 Journal Article
%1 Rietschel:2010:Biol-Psychiatry:20673876
%A Rietschel, M
%A Mattheisen, M
%A Frank, J
%A Treutlein, J
%A Degenhardt, F
%A Breuer, R
%A Steffens, M
%A Mier, D
%A Esslinger, C
%A Walter, H
%A Kirsch, P
%A Erk, S
%A Schnell, K
%A Herms, S
%A Wichmann, H E
%A Schreiber, S
%A Jöckel, K H
%A Strohmaier, J
%A Roeske, D
%A Haenisch, B
%A Gross, M
%A Hoefels, S
%A Lucae, S
%A Binder, E B
%A Wienker, T F
%A Schulze, T G
%A Schmäl, C
%A Zimmer, A
%A Juraeva, D
%A Brors, B
%A Bettecken, T
%A Meyer-Lindenberg, A
%A Müller-Myhsok, B
%A Maier, W
%A Nöthen, M M
%A Cichon, S
%D 2010
%J Biol Psychiatry
%K myPublications
%N 6
%P 578-585
%R 10.1016/j.biopsych.2010.05.038
%T Genome-wide association-, replication-, and neuroimaging study implicates HOMER1 in the etiology of major depression
%U http://www.ncbi.nlm.nih.gov/pubmed/20673876
%V 68
%X Genome-wide association studies are a powerful tool for unravelling the genetic background of complex disorders such as major depression.We conducted a genome-wide association study of 604 patients with major depression and 1364 population based control subjects. The top hundred findings were followed up in a replication sample of 409 patients and 541 control subjects.Two SNPs showed nominally significant association in both the genome-wide association study and the replication samples: 1) rs9943849 (p(combined) = 3.24E-6) located upstream of the carboxypeptidase M (CPM) gene and 2) rs7713917 (p(combined) = 1.48E-6), located in a putative regulatory region of HOMER1. Further evidence for HOMER1 was obtained through gene-wide analysis while conditioning on the genotypes of rs7713917 (p(combined) = 4.12E-3). Homer1 knockout mice display behavioral traits that are paradigmatic of depression, and transcriptional variants of Homer1 result in the dysregulation of cortical-limbic circuitry. This is consistent with the findings of our subsequent human imaging genetics study, which revealed that variation in single nucleotide polymorphism rs7713917 had a significant influence on prefrontal activity during executive cognition and anticipation of reward.Our findings, combined with evidence from preclinical and animal studies, suggest that HOMER1 plays a role in the etiology of major depression and that the genetic variation affects depression via the dysregulation of cognitive and motivational processes.
@article{Rietschel:2010:Biol-Psychiatry:20673876,
abstract = {Genome-wide association studies are a powerful tool for unravelling the genetic background of complex disorders such as major depression.We conducted a genome-wide association study of 604 patients with major depression and 1364 population based control subjects. The top hundred findings were followed up in a replication sample of 409 patients and 541 control subjects.Two SNPs showed nominally significant association in both the genome-wide association study and the replication samples: 1) rs9943849 (p(combined) = 3.24E-6) located upstream of the carboxypeptidase M (CPM) gene and 2) rs7713917 (p(combined) = 1.48E-6), located in a putative regulatory region of HOMER1. Further evidence for HOMER1 was obtained through gene-wide analysis while conditioning on the genotypes of rs7713917 (p(combined) = 4.12E-3). Homer1 knockout mice display behavioral traits that are paradigmatic of depression, and transcriptional variants of Homer1 result in the dysregulation of cortical-limbic circuitry. This is consistent with the findings of our subsequent human imaging genetics study, which revealed that variation in single nucleotide polymorphism rs7713917 had a significant influence on prefrontal activity during executive cognition and anticipation of reward.Our findings, combined with evidence from preclinical and animal studies, suggest that HOMER1 plays a role in the etiology of major depression and that the genetic variation affects depression via the dysregulation of cognitive and motivational processes.},
added-at = {2015-04-09T16:52:25.000+0200},
author = {Rietschel, M and Mattheisen, M and Frank, J and Treutlein, J and Degenhardt, F and Breuer, R and Steffens, M and Mier, D and Esslinger, C and Walter, H and Kirsch, P and Erk, S and Schnell, K and Herms, S and Wichmann, H E and Schreiber, S and J{\"o}ckel, K H and Strohmaier, J and Roeske, D and Haenisch, B and Gross, M and Hoefels, S and Lucae, S and Binder, E B and Wienker, T F and Schulze, T G and Schm{\"a}l, C and Zimmer, A and Juraeva, D and Brors, B and Bettecken, T and Meyer-Lindenberg, A and M{\"u}ller-Myhsok, B and Maier, W and N{\"o}then, M M and Cichon, S},
biburl = {https://www.bibsonomy.org/bibtex/2c17ffe0a95e37933b1a909ecf6085db3/juraeva},
description = {Genome-wide association-, replication-, and neuroimaging study implicates HOMER1 in the etiology of major depression. - PubMed - NCBI},
doi = {10.1016/j.biopsych.2010.05.038},
interhash = {4f0aa8dc630800249fa29d5408c1cdf2},
intrahash = {c17ffe0a95e37933b1a909ecf6085db3},
journal = {Biol Psychiatry},
keywords = {myPublications},
month = sep,
number = 6,
pages = {578-585},
pmid = {20673876},
timestamp = {2015-04-09T17:02:23.000+0200},
title = {Genome-wide association-, replication-, and neuroimaging study implicates HOMER1 in the etiology of major depression},
url = {http://www.ncbi.nlm.nih.gov/pubmed/20673876},
volume = 68,
year = 2010
}