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As much as I like to talk about Data Transparency and try to demystify some of the calculations used in the Clinical Trials, when it comes to the modern genetic studies, I’m lost at sea. They’re doing calculus and I’m still on the multiplication tables just over counting on my fingers. I know that GWAS stands for genome-wide association study<\/font><\/em>, and I sort of know what a SNP [single-nucleotide polymorphism<\/font><\/em>] is. Beyond that, I’m only dimly able to understand how a given study was conducted and what the authors make of their findings, but not able to speak to the quality of the work. So in this case, I’ll say what a SNP is, because these geneticists can talk of little else, and if you talk genetics, you have to throw in SNP [pronounced "snip<\/em>"] every so often to qualify yourself. Remember that the genome [the sequence of nucleotides on the chromosomes] fills a pretty large cabinet and makes for some really monotonous reading.<\/div>\n![](\"http:\/\/1boringoldman.com\/images\/mendel.jpg\")
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A snip<\/em> is a place where some segment on the genome differs among individuals or between paired chromosomes by only a single nucleotide. These areas with only one nucleotide difference are easily found and point to areas of variation within and between individuals. Many classic genetic disorders are caused by SNPs [Sickle Cell Anemia, Thalassemia, Cystic Fibrosis, etc]. That’s it for what I know…<\/p>\n The reason for mentioning this study is that this group took what seems to me to be a unique tack in analyzing the data. They identified SNP groupings that were associated with Schizophrenia compared to controls, identifying genotypes [SNP "sets"] that carried a high risk. But then they did something new. They queried a database of Schizophrenic patients who had been in studies where there was a lot of clinical information [eg C.A.T.I.E.]. They classified those cases by phenotype [clinical characteristics].<\/p>\n Then they tested the different genotypes [SNP "sets"] against the phenotypes [separated clinically] and found correlations that lead them to conclude that "Schizophrenia is a group of heritable disorders caused by a moderate number of separate genotypic networks associated with several distinct clinical syndromes.<\/font><\/strong><\/em>"<\/p>\n The classification of clinical cases they used was way more complicated that that of the days of Kraepelin or Bleuler, and nothing like the DSM-anything. And their method of correlating genotype [genetic SNP sets] with phenotypes [their clinical classification] was no simple spreadsheet, but rather a complex "architecture" [see their figure above]. It says that Schizophrenia is genetic – that it is not an<\/u> entity, but many entities [see a guest post from Sandy Steingard…<\/a>] – "the schizophrenias." The study A couple if months ago, there was another Schizophrenia genetic study in Nature that got wide attention [Biological insights from 108 schizophrenia-associated genetic loci<\/a>] [see Director’s Blog: Mapping the Risk Architecture of Mental Disorders<\/a>]. The recent write-up of that study in the Psychiatric<\/font>News<\/font><\/strong> [Dozens of Schizophrenia Risk Loci Identified<\/a>] was effusive, making analogies to the spires of Dubai and peppered with guest expert speculations. On the other end of the spectrum, Joanna Moncrieff [Critical Psychiatry Network<\/em> and Mad-in-America<\/em>] had a different take [A critique of genetic research on schizophrenia – expensive castles in the air<\/a>], pointing to the massive spending on genetics research with little likely practical yield compared to the lack of attention to the psychosocial needs of these patients. I envy the clarity of such dichotomous convictions. Alas, I always find myself in the middle [in their lifetimes…<\/a>], and want to insert an AND<\/font> for every EITHER\/OR<\/font> into these controversies.<\/p>\n For forty plus years, I’ve seen those slides and figures in books saying that the psychoses have a strong genetic component – and clinical experience has born that out with patients, particularly with Manic-Depressive Illness [classic cases rather than the modern bastardizations]. But just knowing the familial patterns is a factor in diagnosis rather than treatment. For what it’s worth, I believe it, in spite of being of a psychological bent as a clinician. And like almost everyone, when they cracked the genome, I wondered not-if-but-when<\/em> the genetic associations would get clarified. The early attempts were disappointing. I think the DSM-5 Task Force was counting on such breakthroughs to justify their "biologocal" classification scheme – and the research just didn’t come through, much to their chagrin.<\/p>\n![](\"http:\/\/1boringoldman.com\/images\/geno-pheno.gif\")
<\/p>\nimplies<\/strike> says that the clinical presentation and course of these clinical syndromes define unique "diseases<\/u>," each with a physical basis. And that’s a mouthful.<\/p>\n![](\"http:\/\/1boringoldman.com\/images\/mendel-4.gif\")
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