Lithium and Genes

Peter Forster Bipolar Treatment, Psychobiology, Testing

Several studies have suggested that lithium response has a genetic component. Whether someone with bipolar will respond to treatment with lithium seems to be strongly associated with the presence or absence of a family history of response to the medication.

A recent article in the Lancet reports the results of a genome-wide association study of lithium response in 2563 patients collected by 22 participating sites from the International Consortium on Lithium Genetics (ConLiGen).

Lithium response was measured using a well established scale (Alda scale).

The researchers looked for single nucleotide polymorphisms (SNPs) that were associated statistically with lithium response.

Single nucleotide polymorphisms are the most common type of genetic variation among people. Each SNP represents a difference in a single nucleotide. For example, a SNP may replace the nucleotide cytosine (C) with the nucleotide thymine (T) in a certain stretch of DNA.

SNPs occur normally throughout a person’s DNA. They occur once in every 300 nucleotides on average, which means there are roughly 10 million SNPs in the human genome. Most commonly, these variations are found in the DNA between genes. Their occurrence in the DNA between genes is useful as a biological markers, it can help scientists locate genes that are associated with disease.

That is what this study was designed to do.

Genotyped SNPs were used to generate data at more than 6 million sites on the genomes of the subjects.

In the study, a single locus of four linked SNPs on chromosome 21 was significantly associated with lithium response. This suggests that what was identified was one or two genes that are associated with lithium response.

Since response to treatment is rarely associated with one or two genes, it means that many other genetic factors probably exist.

In fact the authors of this article note that the clinical utility of this particular finding is likely to be minimal since the great majority of people who respond positively or negatively to lithium would not be identified by a routine testing for these genetic markers.

Interestingly, there are two genes in that region of chromosome 21: and these are both genes for long, non-coding RNAs (lncRNAs), AL157359.3 and AL157359.4.

DNA is used to create RNA (transcription). RNA, in turn, is used to create proteins (translation). Some sections of DNA do not generate RNA at all, and some create RNA that does not in turn create protein.

DNA-1024x356

Non-coding RNAs are not used to create protein. However, it turns out that non-coding RNAs are much more common than RNAs that do create proteins, most of them probably have no significant role, but some of them are very important in regulating gene expression. In other words, these RNA’s play a role in regulating DNA transcription on other sections of the genome.

References

Hou L, Heilbronner U, Degenhardt F, Adli M, Akiyama K, Akula N, Ardau R, Arias B, Backlund L, Banzato CE, Benabarre A, Bengesser S, Bhattacharjee AK, Biernacka JM, Birner A, Brichant-Petitjean C, Bui ET, Cervantes P, Chen GB, Chen HC, Chillotti C, Cichon S, Clark SR, Colom F, Cousins DA, Cruceanu C, Czerski PM, Dantas CR, Dayer A, Étain B, Falkai P, Forstner AJ, Frisén L, Fullerton JM, Gard S, Garnham JS, Goes FS, Grof P, Gruber O, Hashimoto R, Hauser J, Herms S, Hoffmann P, Hofmann A, Jamain S, Jiménez E, Kahn JP, Kassem L, Kittel-Schneider S, Kliwicki S, König B, Kusumi I, Lackner N, Laje G, Landén M, Lavebratt C, Leboyer M, Leckband SG, Jaramillo CA, MacQueen G, Manchia M, Martinsson L, Mattheisen M, McCarthy MJ, McElroy SL, Mitjans M, Mondimore FM, Monteleone P, Nievergelt CM, Nöthen MM, Ösby U, Ozaki N, Perlis RH, Pfennig A, Reich-Erkelenz D, Rouleau GA, Schofield PR, Schubert KO, Schweizer BW, Seemüller F, Severino G, Shekhtman T, Shilling PD, Shimoda K, Simhandl C, Slaney CM, Smoller JW, Squassina A, Stamm T, Stopkova P, Tighe SK, Tortorella A, Turecki G, Volkert J, Witt S, Wright A, Young LT, Zandi PP, Potash JB, DePaulo JR, Bauer M, Reininghaus EZ, Novák T, Aubry JM, Maj M, Baune BT, Mitchell PB, Vieta E, Frye MA, Rybakowski JK, Kuo PH, Kato T, Grigoroiu-Serbanescu M, Reif A, Del Zompo M, Bellivier F, Schalling M, Wray NR, Kelsoe JR, Alda M, Rietschel M, McMahon FJ, Schulze TG. Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study. Lancet. 2016 Jan 21. pii: S0140-6736(16)00143-4. doi: 10.1016/S0140-6736(16)00143-4. [Epub ahead of print] PubMed PMID: 26806518.

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