Despite much research in recent years, including a study that establishes the heritability of bipolar disorder at 85% (confirming what families and clinicians have known for decades), the precise genetic basis of bipolar disorder remains elusive. Single-gene studies have identified promising candidates here and there, but genome-wide association studies have failed to produce replicable results.

Geneticist Dr. Daniel Macarthur recently wrote a super blog post about bipolar gene studies. He explains why several genome-wide association studies involving thousands of patients and controls have not had strong or replicable results. It seems bipolar associations have not been found in variations of the commonly tested genes. Macarthur says that it’s more likely the variations are more rare and haven’t been picked up by the studies, but that the advent of whole-genome sequencing should turn up those elusive markers.

I wrote to Macarthur to ask him to clarify the difference between genome-wide association studies (GWAS) and whole-genome sequencing, for those of us who aren’t familiar with all the terminology. His reply:

GWAS can be quite powerful at capturing common variations underlying
disease risk, but they can’t “see” other types of variation such as rare variants (anything with a frequency of less than 5%), or insertions and deletions. Any effect of these sorts of variations on bipolar risk will be completely missed by current GWAS technology, no
matter how large their sample sizes.

Whole-genome sequencing is a different (and currently impossible) strategy: rather than determining the sequence at a million sites, you sequence EVERYTHING. Whole-genome sequencing would allow researchers to get access to the rare variants and insertion/deletion polymorphisms missed by current GWAS technology.

Research on single genes, like knockout mouse studies, are likely to mesh with whole-genome sequencing to produce stronger results, and Macarthur expects that in the next few years as the cost of whole-genome sequencing comes down (right now it costs about $350,000) we’ll see an explosion in our knowledge of genetic ties not only in bipolar but a wide array of illnesses.

Meanwhile, about those home-testing kits we’re seeing on the market? As John has also suggested previously here, don’t waste your money. Wait until research firmly backs them up.

Read more at Genetic Future.

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Bipolar Genomics - World of Psychology (4/19/2008)

    Last reviewed: By John M. Grohol, Psy.D. on 18 Apr 2008
    Published on PsychCentral.com. All rights reserved.