X chromosome and suicide.
Suicide completion rates are significantly higher in males than females in most societies. Although gender differences in suicide rates have been partially explained by environmental and behavioral factors, it is possible that genetic factors, through differential expression between genders, may also help explain gender moderation of suicide risk. This study investigated X-linked genes in suicide completers using a two-step strategy. We first took advantage of the genetic structure of the French-Canadian population and genotyped 722 unrelated French-Canadian male subjects, of whom 333 were suicide completers and 389 were non-suicide controls, using a panel of 37 microsatellite markers spanning the entire X chromosome. Nine haplotype windows and several individual markers were associated with suicide. Significant results aggregated primarily in two regions, one in the long arm and another in the short arm of chromosome X, limited by markers DXS8051 and DXS8102, and DXS1001 and DXS8106, respectively. The second stage of the study investigated differential brain expression of genes mapping to associated regions in Brodmann areas 8/9, 11, 44 and 46, in an independent sample of suicide completers and controls. Six genes within these regions, Rho GTPase-activating protein 6, adaptor-related protein complex 1 sigma 2 subunit, glycoprotein M6B, ribosomal protein S6 kinase 90  kDa polypeptide 3, spermidine/spermine N(1)-acetyltransferase 1 and THO complex 2, were found to be differentially expressed in suicide completers.
Fiori
L M
LM
McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.
Zouk
H
H
Himmelman
C
C
Turecki
G
G
D000123:Acetyltransferases / Q000235:genetics; D034002:Adaptor Protein Complex sigma Subunits / Q000235:genetics; D000328:Adult; D001921:Brain; D002170:Canada; D016009:Chi-Square Distribution; D002874:Chromosome Mapping; D003863:Depression / Q000150:complications / Q000235:genetics / Q000473:pathology; D020690:GTPase-Activating Proteins / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D050172:Genes, X-Linked / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011569:Psychiatric Status Rating Scales; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics; D013405:Suicide / Q000523:psychology*; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D034002:Adaptor Protein Complex sigma Subunits; D020690:GTPase-Activating Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D000099228:Diamine N-Acetyltransferase; C109971:ARHGAP6 protein, human; C484160:GPM6B protein, human