20 research outputs found
Genomic variants in the FTO gene are associated with sporadic amyotrophic lateral sclerosis in Greek patients
Background: Amyotrophic lateral sclerosis (ALS) is a devastating disease whose complex pathology has been
associated with a strong genetic component in the context of both familial and sporadic disease. Herein, we
adopted a next-generation sequencing approach to Greek patients suffering from sporadic ALS (together with their
healthy counterparts) in order to explore further the genetic basis of sporadic ALS (sALS).
Results: Whole-genome sequencing analysis of Greek sALS patients revealed a positive association between FTO
and TBC1D1 gene variants and sALS. Further, linkage disequilibrium analyses were suggestive of a specific diseaseassociated
haplotype for FTO gene variants. Genotyping for these variants was performed in Greek, Sardinian, and
Turkish sALS patients. A lack of association between FTO and TBC1D1 variants and sALS in patients of Sardinian and
Turkish descent may suggest a founder effect in the Greek population. FTO was found to be highly expressed in
motor neurons, while in silico analyses predicted an impact on FTO and TBC1D1 mRNA splicing for the genomic
variants in question.
Conclusions: To our knowledge, this is the first study to present a possible association between FTO gene variants
and the genetic etiology of sALS. In addition, the next-generation sequencing-based genomics approach coupled
with the two-step validation strategy described herein has the potential to be applied to other types of human
complex genetic disorders in order to identify variants of clinical significance
Author Correction: Cross sectional evaluation of the gut-microbiome metabolome axis in an Italian cohort of IBD patients
Correction to: Scientific Reports https://doi.org/10.1038/s41598-017-10034-5, published online 25 August 2017