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Marti et al. J Transl Genet Genom 2020;4:104-13 I http://dx.doi.org/10.20517/jtgg.2020.10 Page 111

CONCLUSION
Regardless of the progress made so far, the overall picture is still highly complex and there are plenty of
future challenges to be addressed for ID. Is ID a single entity amenable to the application of standard
genetic analysis methodologies? Are genetic variants and environmental influences responsible for ID also
involved in the normal distribution of IQ? Which of the identified variants are responsible for the final
phenotype? What are the contributions of single genes versus that of the genomic makeup? Are the variant
effects constitutive, or do they appear only in response to specific environmental challenges? How do we
understand the epigenetic contribution to ID? And what are the biological nodes that are promising for
therapeutic options? With the amount of genetic information already available, it is clear that the level of
complexity in ID is immense and there is an entire genome to investigate and understand. Stratification
and careful consideration of ID grouping is also a must. We expect future research strategies to involve
the development of animal models and/or in vitro molecular functional studies which will provide
reliable, accessible and cost-effective platforms to perform functional tests of novel variants, and accelerate
discovery of the biological functions underlying genetic forms of ID and enhance the translation to clinical
care.

DECLARATIONS
Acknowledgments
We thank Erna M. L. Stoddart for English proofreading and formatting assistance.

Authors’ contributions
Manuscript writing: Marti M, Millan MIP, Young JI
Conception, design and manuscript writing: Walz K

Availability of data and materials
Not applicable.

Financial support and sponsorship
None.

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2020.

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