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March 14, 2014
The Genetics of Bipolar Disorder: What A Tangle
Here's a brave attempt to look for genetic markers of bipolar disorder. The authors studied 388 Old Order Amish sufferers, doing thorough SNP analysis on the lot and total sequencing on fifty of them. There were many parent-child relationships in the set, which gave a chance for further discrimination. And the result:
. . .despite the in-depth genomic characterization of this unique, large and multigenerational pedigree from a genetic isolate, there was no convergence of evidence implicating a particular set of risk loci or common pathways. The striking haplotype and locus heterogeneity we observed has profound implications for the design of studies of bipolar and other related disorders.
If you look around the literature, you'll find numerous smaller studies also trying to find genetic markers for bipolar disorder, and many of these propose possible candidate loci. But very few of them seem to agree, and this new study doesn't seem to confirm any of them. The authors hold out some hope for still larger cohorts and more comprehensive sequencing, and that's certainly the way to go. But if there were anything close to a simple genetic sequence for bipolar disorder, it would have been found by now. Like many other diseases (and not just those of the central nervous system), it's probably a phenotype that can be realized by a whole range of mechanisms, an alternate state of physiology that the system can slip into through a combination of genetic and environmental effects. And while there there may not be a thousand ways to get there, there sure aren't just a couple.
Dealing with these "network diseases" is going to keep us busy for quite a while to come. The best hope, as far as I can see, is for less complexity downstream. Maybe these various susceptibilities and tendencies all slide towards a similar disease process which can be modified. Looking back to the genetic causes for understanding sure hasn't worked out so far; maybe advances in studying brain function and patterns of neurotransmission will shed some light. Although if you're having to look to that area to bail you out. . .
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