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Genome-wide copy number variation study associates metabotropic glutamate receptor gene networks with attention deficit hyperactivity disorder

(2012) NATURE GENETICS. 44(1). p.78-84
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Abstract
Attention deficit hyperactivity disorder (ADHD) is a common, heritable neuropsychiatric disorder of unknown etiology. We performed a whole-genome copy number variation (CNV) study on 1,013 cases with ADHD and 4,105 healthy children of European ancestry using 550,000 SNPs. We evaluated statistically significant findings in multiple independent cohorts, with a total of 2,493 cases with ADHD and 9,222 controls of European ancestry, using matched platforms. CNVs affecting metabotropic glutamate receptor genes were enriched across all cohorts (P = 2.1 x 10(-9)). We saw GRM5 (encoding glutamate receptor, metabotropic 5) deletions in ten cases and one control (P = 1.36 x 10(-6)). We saw GRM7 deletions in six cases, and we saw GRM8 deletions in eight cases and no controls. GRM1 was duplicated in eight cases. We experimentally validated the observed variants using quantitative RT-PCR. A gene network analysis showed that genes interacting with the genes in the GRM family are enriched for CNVs in similar to 10% of the cases (P = 4.38 x 10(-10)) after correction for occurrence in the controls. We identified rare recurrent CNVs affecting glutamatergic neurotransmission genes that were overrepresented in multiple ADHD cohorts.
Keywords
ADHD, REPLICATION, CHILDREN, DEFICIT/HYPERACTIVITY-DISORDER, MICE LACKING, SNP GENOTYPING DATA, SPONTANEOUSLY HYPERTENSIVE-RAT, HIDDEN-MARKOV MODEL, AUTISM SPECTRUM DISORDERS, LINKAGE

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Citation

Please use this url to cite or link to this publication:

Chicago
Elia, Josephine, Joseph T Glessner, Kai Wang, Nagahide Takahashi, Corina J Shtir, Dexter Hadley, Patrick MA Sleiman, et al. 2012. “Genome-wide Copy Number Variation Study Associates Metabotropic Glutamate Receptor Gene Networks with Attention Deficit Hyperactivity Disorder.” Nature Genetics 44 (1): 78–84.
APA
Elia, J., Glessner, J. T., Wang, K., Takahashi, N., Shtir, C. J., Hadley, D., Sleiman, P. M., et al. (2012). Genome-wide copy number variation study associates metabotropic glutamate receptor gene networks with attention deficit hyperactivity disorder. NATURE GENETICS, 44(1), 78–84.
Vancouver
1.
Elia J, Glessner JT, Wang K, Takahashi N, Shtir CJ, Hadley D, et al. Genome-wide copy number variation study associates metabotropic glutamate receptor gene networks with attention deficit hyperactivity disorder. NATURE GENETICS. 2012;44(1):78–84.
MLA
Elia, Josephine, Joseph T Glessner, Kai Wang, et al. “Genome-wide Copy Number Variation Study Associates Metabotropic Glutamate Receptor Gene Networks with Attention Deficit Hyperactivity Disorder.” NATURE GENETICS 44.1 (2012): 78–84. Print.
@article{3022195,
  abstract     = {Attention deficit hyperactivity disorder (ADHD) is a common, heritable neuropsychiatric disorder of unknown etiology. We performed a whole-genome copy number variation (CNV) study on 1,013 cases with ADHD and 4,105 healthy children of European ancestry using 550,000 SNPs. We evaluated statistically significant findings in multiple independent cohorts, with a total of 2,493 cases with ADHD and 9,222 controls of European ancestry, using matched platforms. CNVs affecting metabotropic glutamate receptor genes were enriched across all cohorts (P = 2.1 x 10(-9)). We saw GRM5 (encoding glutamate receptor, metabotropic 5) deletions in ten cases and one control (P = 1.36 x 10(-6)). We saw GRM7 deletions in six cases, and we saw GRM8 deletions in eight cases and no controls. GRM1 was duplicated in eight cases. We experimentally validated the observed variants using quantitative RT-PCR. A gene network analysis showed that genes interacting with the genes in the GRM family are enriched for CNVs in similar to 10\% of the cases (P = 4.38 x 10(-10)) after correction for occurrence in the controls. We identified rare recurrent CNVs affecting glutamatergic neurotransmission genes that were overrepresented in multiple ADHD cohorts.},
  author       = {Elia, Josephine and Glessner, Joseph T and Wang, Kai and Takahashi, Nagahide and Shtir, Corina J and Hadley, Dexter and Sleiman, Patrick MA and Zhang, HaitaoT and Kim, Cecilia E and Robison, Reid and Lyon, Gholson J and Flory, James H and Bradfield, Jonathan P and Imielinski, Marcin and Hou, Cuiping and Frackelton, Edward C and Chiavacci, Rosetta M and Sakurai, Takeshi and Rabin, Cara and Middleton, Frank A and Thomas, Kelly A and Garris, Maria and Mentch, Frank and Freitag, Christine M and Steinhausen, Hans-Christoph and Todorov, Alexandre A and Reif, Andreas and Rothenberger, Aribert and Franke, Barbara and Mick, Eric O and Roeyers, Herbert and Buitelaar, Jan and Lesch, Klaus-Peter and Banaschewski, Tobias and Ebstein, Richard P and Mulas, Fernando and Oades, Robert D and Sergeant, Joseph and Barke, Edmund and Renner, Tobias J and Romanos, Marcel and Romanos, Jasmin and Warnke, Andreas and Walitza, Susanne and Meyer, Jobst and P{\'a}lmason, Haukur and Seitz, Christiane and Loo, Sandra K and Smalley, Susan L and Biederman, Joseph and Kent, Lindsey and Asherson, Philip and Anney, Richard JL and Gaynor, J William and Shaw, Philip and Devoto, Marcella and White, Peter S and Grant, Struan FA and Buxbaum, Joseph D and Rapoport, Judith L and Williams, Nigel M and Nelson, Stanley F and Faraone, Stephen V and Hakonarson, Hakon},
  issn         = {1061-4036},
  journal      = {NATURE GENETICS},
  keyword      = {ADHD,REPLICATION,CHILDREN,DEFICIT/HYPERACTIVITY-DISORDER,MICE LACKING,SNP GENOTYPING DATA,SPONTANEOUSLY HYPERTENSIVE-RAT,HIDDEN-MARKOV MODEL,AUTISM SPECTRUM DISORDERS,LINKAGE},
  language     = {eng},
  number       = {1},
  pages        = {78--84},
  title        = {Genome-wide copy number variation study associates metabotropic glutamate receptor gene networks with attention deficit hyperactivity disorder},
  url          = {http://dx.doi.org/10.1038/ng.1013},
  volume       = {44},
  year         = {2012},
}

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