Research Highlights

Genomic study unveils genetic variants in brain

Published online 16 September 2014

Moheb Costandi

In one of the largest studies of its kind to date, an international team of researchers has identified numerous genetic variations associated with the regulation of gene expression in different regions of the human brain1.

Recent advances in DNA sequencing technology allow for the analysis of entire genomes quickly and the identification of millions of single nucleotide polymorphisms (SNPs) associated with a wide range of neurological and psychiatric disorders. 

Most of these variants lie within non-coding regions of the genome, and exert their effects by regulating gene expression. One such regulatory mechanism is a process called alternative splicing, by which separate coding regions of the same gene (or exons) are brought together in different combinations to produce multiple versions of the same protein.  

Alternative splicing is known to occur widely throughout the human brain, with more than 90% of genes expressed in the organ being alternatively spliced. Very little is known about this process. 

To investigate the researchers, including Daniah Trabsuni of the King Faisal Specialist Hospital and Research Centre in Riyadh, took post-mortem tissue samples from the brains of 134 healthy individuals and isolated DNA and RNA from 10 different brain regions. 

They sequenced the nucleic acids to measure gene expression levels across the whole genome, and then subjected the sequence data to expression quantitative trait loci (eQTL) analysis. 

They identified more than 30,000 eQTL signals, accounting for 23.1% of the SNPs known to be associated with neurological disorders, all lying within non-coding regions less than 1 million base pairs away from their target gene2

“The regulatory information within the genome is very rich and region-specific,” says neurogeneticist Mina Ryten of University College London, a co-senior of the study.

“Now we want to examine the RNA samples further, as this allows us to analyse gene expression and splicing more accurately.” 


  1. Ramasamy, A., et al. Genetic variability in the regulation of gene expression in ten regions of the human brain. Nature Neurosci. (2014)
  2. The entire data set is publicly available at