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Chunk #204 — VII. Classes of genes that are identified in multiple GWA samples for multiple phenotypes: Focus on cell adhesion related genes

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Molecular genetics of addiction and related heritable phenotypes: genome-wide association approaches identify "connectivity constellation" and drug target genes with pleiotropic effects.
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The rs8019381 SNP was located 23 bp 3’ from the 3’ end of exon 23, near a branch point that could change the splicing of NRXN3 primary transcripts [220, 221]. In mRNAs isolated from postmortem cerebral cortex, individuals with one or two copies of the minor rs8019381 T allele expressed less of the major transmembrane isoform ex22a24b and the minor transmembrane isoform ex22a24a mRNA levels than did CC homozygotes (p= 0.0008 and 0.021 for genotypes by two-tailed Mann Whitney test, respectively). By contrast, expression of the major ex22a23a soluble isoform did not correlate with rs8019381 genotype (p= 0.171 by two-tailed Mann Whitney test). As a consequence, ratios between transmembrane and soluble isoforms were significantly increased in individuals with one or two T alleles in comparison to CC homozygotes (p = 0.018, two-tailed Mann Whitney test).