Genetic Predictors of Lithium Response

U Heilbronner

doi:10.31363/2313-7053-2019-4-1-26-27

Abstract

Lithium remains a first-line pharmacological treatment of bipolar disorder (BD). However, treatment response is heterogeneous, with several lines of evidence implicating genetic factors. Unfortunately, neither hypothesis-driven approaches nor initial genome-wide association studies (GWAS) were successful in identifying genetic drivers of response heterogeneity, probably due to low statistical power and different phenotype measurements. Recently, a GWAS of the Consortium of Lithium Genetics (ConLiGen) has identified four single nucleotide polymorphisms (SNPs) mediating response to lithium, located in genes for two long non-coding RNAs. This success was only possible by international collaboration and the use of an established lithium response scale. The findings await further replication.

Highlights

Individual response is heterogeneous, only about 30% of bipolar disorder (BD) patient treated with lithium robustly respond to it (Garnham et al, 2007)
There is a pressing need to identify predictors of lithium response that may eventually serve as biomarkers
The heritability of lithium response estimated from single nucleotide polymorphisms (SNPs) is around 0.30, i.e. about 30% of the total variation in lithium response can be explained by SNPs (Song et al, 2017)

Summary

Introduction

Недавно Международный консорциум по фармакогенетике препаратов лития (ConLiGen) провел GWAS и идентифицировал четыре однонуклеотидных полиморфизма (SNP), опосредующих ответ на литий и расположенных в генах двух длинных некодирующих РНК. Lithium remains a first-line pharmacological treatment of BD, and is effective in reducing affective episodes, suicide risk, and overall mortality (Papiol, Schulze, & Alda, 2018). As previous studies have found evidence that lithium response is a familial trait (Grof et al, 2002), this implicates that there may be genetic factors mediating treatment response.

Results

Conclusion