Genome-wide copy number variation study associates metabotropic glutamate receptor gene networks with attention deficit hyperactivity disorder. Academic Article uri icon

Overview

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 × 10(-9)). We saw GRM5 (encoding glutamate receptor, metabotropic 5) deletions in ten cases and one control (P = 1.36 × 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 ∼10% of the cases (P = 4.38 × 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.

authors

  • Elia, Josephine
  • Glessner, Joseph T
  • Wang, Kai
  • Takahashi, Nagahide
  • Shtir, Corina J
  • Hadley, Dexter
  • Sleiman, Patrick M A
  • Zhang, Haitao
  • Kim, Cecilia E
  • Robison, Reid
  • Lyon, Gholson J
  • Flory, James
  • Bradfield, Jonathan P
  • Imielinski, Marcin
  • Hou, Cuiping
  • Frackelton, Edward C
  • Chiavacci, Rosetta M
  • Sakurai, Takeshi
  • Rabin, Cara
  • Middleton, Frank A
  • Thomas, Kelly A
  • Garris, Maria
  • Mentch, Frank
  • Freitag, Christine M
  • Steinhausen, Hans-Christoph
  • Todorov, Alexandre A
  • Reif, Andreas
  • Rothenberger, Aribert
  • Franke, Barbara
  • Mick, Eric O
  • Roeyers, Herbert
  • Buitelaar, Jan
  • Lesch, Klaus-Peter
  • Banaschewski, Tobias
  • Ebstein, Richard P
  • Mulas, Fernando
  • Oades, Robert D
  • Sergeant, Joseph
  • Sonuga-Barke, Edmund
  • Renner, Tobias J
  • Romanos, Marcel
  • Romanos, Jasmin
  • Warnke, Andreas
  • Walitza, Susanne
  • Meyer, Jobst
  • Pálmason, Haukur
  • Seitz, Christiane
  • Loo, Sandra K
  • Smalley, Susan L
  • Biederman, Joseph
  • Kent, Lindsey
  • Asherson, Philip
  • Anney, Richard J L
  • Gaynor, J William
  • Shaw, Philip
  • Devoto, Marcella
  • White, Peter S
  • Grant, Struan F A
  • Buxbaum, Joseph D
  • Rapoport, Judith L
  • Williams, Nigel M
  • Nelson, Stanley F
  • Faraone, Stephen V
  • Hakonarson, Hakon

publication date

  • December 4, 2011

Research

keywords

  • Attention Deficit Disorder with Hyperactivity
  • DNA Copy Number Variations
  • Gene Regulatory Networks

Identity

PubMed Central ID

  • PMC4310555

Scopus Document Identifier

  • 84655176643

Digital Object Identifier (DOI)

  • 10.1038/ng.1013

PubMed ID

  • 22138692

Additional Document Info

volume

  • 44

issue

  • 1