An extensive study recently published in the esteemed Nature Communications journal aimed to identify genetic causes of developmental disability and milder intellectual disabilities. The findings are based on data collected from 440 patients in northern Finland within the regions of the Oulu University Hospital and the Northern Ostrobothnia Hospital District.
Patients for whom the cause of their disability was still unknown were enrolled in the study. More than half of the study subjects had a milder form of intellectual disability, as the researchers wished to particularly focus on this little-investigated patient group.
Intellectual disability is a relatively common disorder. The patients’ intellectual functioning is significantly poorer than among the average population, in addition to which they face challenges in social situations and everyday life. Less than half a percent of the population have a severe developmental disability, but milder intellectual disabilities occur in as much as 2–3% of the population.
“The study focused on northern Finland, since intellectual disabilities are known to be somewhat more common there compared to southern and western Finland,” explains Elmo Saarentaus, who is preparing his doctoral dissertation on the topic at the University of Helsinki.
The sequences of the genome that function as coders, more commonly known as genes, were thoroughly examined in all study subjects, and genetic variants found in patients with developmental disabilities were compared with the genome of 11,000 healthy Finns.
In addition to identifying individual gene defects, the researchers combined information on all known common genetic factors associated with intellectual development, educational level and schizophrenia to compute an individual genetic risk score for each study subject.
The likely genetic cause of the developmental disorder was identified in approximately every fifth study participant. Furthermore, the researchers discovered several new gene defects that may potentially predispose individuals to developmental disability. A gene known as CRADD turned out to be of particular interest; a defect in this gene was found that is over 50 times more frequent in the Finnish population than elsewhere in Europe. Three study subjects had inherited a defective copy of this gene, which affects brain development, from both parents.
“Our findings demonstrated that patients with a more severe intellectual disability were more likely to have a clear gene defect in genes associated with intellectual development or a copy number variation affecting extensive genomic regions. Then again, the same genes accounted less often for milder learning disorders,” notes Mitja Kurki, the principal author of the study.
The genetic risk score for educational attainment proved to be higher in patients suffering from mild intellectual disability, making the combined effect of thousands of common variants a probable explanation specifically for mild developmental disorders.
“The findings further consolidate a theory set forth earlier, according to which milder learning disorders are within the normal range of cognitive capacity variation, in which the joint effect of common genetic risk factors have a significant role,” says Professor Aarno Palotie, who headed the study at the Institute for Molecular Medicine Finland (FIMM), University of Helsinki.
“It should be kept in mind that genetic predisposition to intellectual disability remains for the most part unexplained. Further studies will certainly identify both common and rare genetic risk factors,” Palotie notes.
The study was carried out in collaboration by researchers from the University of Oulu, the National Institute for Health and Welfare and the Broad Institute.
Original publication: Kurki MI, Saarentaus E, Pietiläinen O, Gormley P, Lal D, Kerminen S, Torniainen-Holm M, Hämäläinen E, Rahikkala E, Keski-Filppula R, Rauhala M, Korpi-Heikkilä S, Komulainen-Ebrahim J, Helander H, Vieira P, Männikkö M, Peltonen M, Havulinna AS, Salomaa V, Pirinen M, Suvisaari J, Moilanen JS, Körkkö J, Kuismin O, Daly MJ, Palotie A. Contribution of rare and common variants to intellectual disability in a sub-isolate of Northern Finland. Nature Communications 2019 Jan 24;10(1):410. doi: 10.1038/s41467-018-08262-y.