title: Association of the human kainate receptor GluR7 gene (GRIK3) with recurrent major depressive disorder.
abstract: The etiology of mood disorders remains elusive, despite our increasing understanding of the neurotransmitter systems and brain regions that are involved. We performed a large family-based association study to test if the human kainate receptor GluR7 gene (GRIK3) is associated with bipolar disorder (BP) or recurrent major depressive disorder (R-MDD). One hundred fifty-three multiplex BP families from the National Institute of Mental Health (NIMH) Genetics Initiative on Bipolar Disorder were analyzed with the transmission disequilibrium test (TDT). We detected a significant linkage disequilibrium (LD) indicated by preferential maternal transmission of the GluR7 S310 allele to R-MDD patients (P = 0.012), but not to bipolar I disorder (BPI) patients (P = 1.00). We performed a second independent study by applying the TDT in 81 parent-offspring triads from families that inherit recurrent early-onset major depressive disorder (RE-MDD). The results from this second study showed only a suggestive maternal association (P = 0.068). Our findings imply that the GluR7 gene is a susceptibility factor in R-MDD and that the glutamatergic receptor system plays a critical role in the disease etiology.
authors.affiliation: Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, California, USA. jschiffer@acadia-pharm.com
authors.forename: H H
authors.initials: HH
authors.lastname: Schiffer
authors.forename: S F
authors.initials: SF
authors.lastname: Heinemann
mesh_terms: D000483:Alleles; D001483:Base Sequence; D001714:Bipolar Disorder / Q000235:genetics; D004247:DNA / Q000235:genetics; D003865:Major Depressive Disorder / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D009035:Mothers; D018092:Kainic Acid Receptors / Q000235:genetics*; D012008:Recurrence; D000097808:GluK3 Kainate Receptor
chemical_list: D004247:DNA; D018092:Kainic Acid Receptors; D000097808:GluK3 Kainate Receptor