MedicalResearch : What is the background for this study?
Prof. Reymond: Though a subset of recurrent DNA copy number variants (differing numbers of copies of genetic sequence at locations in the genome; CNVs) with rare population prevalence are known to have strong impact on carrier’s health, up to now their association with phenotypes such as intellectual disability has been almost exclusively evaluated in clinical context using individuals ascertained for diagnostics of developmental disorders. Thus the contribution of these genetic variants to health, cognition and life quality in the general population remains unclear. We used a population biobank, that of Estonia (Estonian Genome Center, University of Tartu), which contains samples from 52,000 adult participants (representative 5% of the country’s adult population), a British birth cohort (The Avon Longitudinal Study of Parents and Children; ALSPAC) and two more population-based cohorts from the USA and Italy to explore the consequences of CNVs in presumptively healthy populations.
MedicalResearch : What are the main findings?
Prof. Reymond: Rare recurrent CNVs known to be causative for specific syndromes (termed genomic disorders) have a global population prevalence of around 1%. Contrary to popular assumption that carriers of these syndromic CNVs identified in unselected, but assumed to be healthy, adult population cohorts are asymptomatic, we found that they are associated with unrecognized, but serious clinical sequelae.
Additionally our results showed that individually rare (less than 1 in 2000 individuals) but collectively common (around 10% of population) intermediate-size CNVs are negatively associated with carriers’ educational attainment. Altogether our results suggest that the life quality of at least 1 of 40 people might be negatively affected by rare CNVs.
MedicalResearch : What should clinicians and patients take away from your report?
Prof. Reymond: In addition, none of the biobank participants identified as carriers of known syndromic CNVs were previously diagnosed with a genetic disease. However, 70% of them have reached adulthood suffering from clinical problems, some of these as severe as congenital anomalies, neuropathies, neuropsychiatric and cognitive disturbances, extreme obesity, reproductive problems, that are most likely caused by the genetic alterations “incidentally” found in this study. It suggests that despite strong negative effect from their genetic makeup these individuals have escaped the attention of the medical genetic system and not received proper examination and counseling although genotype-based approach in medical management could significantly improve their life quality.
MedicalResearch : What recommendations do you have for future research as a result of this study?
Prof. Reymond: While our results were replicated in three geographically-distinct populations from the United Kingdom, Minnesota, USA and Italy and using different measures of cognition (e.g. Standard Assessment Tests (SATs) scores in teenagers, FSIQ and mean educational attainment (i.e. the highest level of education reached) in adults, further validation of these findings in additional population groups are warranted given the potential implications of this observation for genomics research, clinical care, and public health.
Our study also shows that widely-used population cohorts cannot be considered as “normal healthy carriers” pinpointing that the precise understanding of the effect of a particular rare CNVs we should phenotypically investigate the individuals identified in clinical cohorts, as well as the carriers found in unselected populations.
The understanding of the impact of genetic variants on an individual’s health and how they affect the society in general will help translating the advances of human genomics sciences into personalized health and social care.