What can rare variant genetics tell us about cognition and intellectual difficulties?

Excerpt

This month we discuss three types of rare genomic variation and specifically how rare variants impact on cognition and behaviour. Each of the highlighted studies employs a different outcome measure: diagnosis of autism spectrum disorder or intellectual difficulties; performance on cognitive testing; and the number of years in education. All harness the extreme power of massively parallel sequencing or genomic arrays together with innovative bioinformatic analyses. The first study identifies ‘ultra-rare variation’, these are variants that are never, or almost never, seen in the unaffected population. The second identifies larger areas of rearranged genomic DNA which change the gene dosage for one or many genes, termed copy number variants. These variants may cluster in previously recognised sites or they may exist idiosyncratically. The third study uses a strategy to focus on variation at the loci that vary most between us and other species and are, therefore, thought to be of special significance for identifying what defines the human species; communication and civilised behaviour. Genomic areas that are highly divergent are known as human-accelerated regions (HARs) and damaging mutations in these areas may be more likely to cause a cognitive or behavioural phenotype. …