Rs17026688

rs17026688 is a SNP located in an intron of the glutamate decarboxylase-like 1 GADL1 gene. It is linked to rs17026651, and both are 100% linked to a 1 base deletion known as 'GADL1 IVS8+48delG' (rs201973599).

In a study of ~1,700 patients of Han Chinese descent with bipolar disorder, researchers discovered that almost all of the patients who responded well to lithium treatment had at least one IVS8+48delG GADL1 allele. Initially, the researchers were focused on two nearby SNPs, rs17026688 and rs17026651, that turned out to be proxies (due to being in high linkage disequilibrium) for the deletion variant. rs17026688(T) is the "response allele", meaning that at least in these Asian patients, bipolar patients who are carriers of at least one (T) allele are predicted to respond well to lithium treatment; rs17026688(C;C) patients are predicted to respond poorly.

The odds ratios and probabilities for this study are so high that the authors are able to calculate sensitivity, specificity, and positive and negative predictive values (PPV; NPV) for the connection between this DNA variant and being a bipolar patient who will respond well (or not) to lithium treatment. In a pooled cohort of ~400 patients, roughly divided equally between those responding well to lithium or not, the odds ratios, p values, sensitivity, specificity, PPV and NPV were around 80, 1 x 10e-50, 93%, 87%, 83% and 95%, respectively. To put it another way, while overall about half of all patients had a response allele and half didn't, only 1 in 14 patients who responded well to lithium lacked a response allele, and only 1 in 8 of those who did not respond well had a response allele. The authors naturally suggest the use of these SNPs as useful biomarkers for which patients with bipolar disorder will respond well to lithium treatment, and they also intend to (1) look for additional GADL1 gene variants acting similarly, especially in non-Asian populations given the rarity of this particular deletion variant outside of Asian population, and (2) see if these variants influence lithium treatment outcomes in other affective disorders such as major depressive disorder.


 * is_associated_with_disease::Major depressive disorder
 * is_associated_with_disease::Bipolar disorder