Meta-analysis of genes in commercially available nutrigenomic tests denotes lack of association with dietary intake and nutrient-related pathologies

Nutrigenomics is an emerging discipline that aims to investigate how individual genetic composition correlates with dietary intake, as well as how nutrition influences gene expression. Herein, the fundamental question relates to the value of nutrigenomics testing on the basis of the currently available scientific evidence. A thorough literature search has been conducted in PubMed scientific literature database for nutrigenomics research studies on 38 genes included in nutrigenomics tests provided by various private genetic testing laboratories. Data were subsequently meta-analyzed to identify possible associations between the genes of interest and dietary intake and/or nutrient-related pathologies. Data analysis occurred according to four different models due to data sparsity and inconsistency. Data from 524,592 individuals (361,153 cases and 163,439 controls) in a total of 1,170 entries were obtained. Conflicting findings indicated that there was a great incompatibility regarding the associations (or their absence) identified. No specific-and statistically significant-association was identified for any of the 38 genes of interest. In those cases, where a weak association was demonstrated, evidence was based on a limited number of studies. As solid scientific evidence is currently lacking, commercially available nutrigenomics tests cannot be presently recommended. Notwithstanding, the need for a thorough and continuous nutrigenomics research is evident as it is a highly promising tool towards precision medicine

Novel genetic risk variants for pediatric celiac disease

Background: Celiac disease is a complex chronic immune-mediated disorder of the small intestine. Today, the pathobiology of the disease is unclear, perplexing differential diagnosis, patient stratification, and decision-making in the clinic. Methods: Herein, we adopted a next-generation sequencing approach in a celiac disease trio of Greek descent to identify all genomic variants with the potential of celiac disease predisposition. Results: Analysis revealed six genomic variants of prime interest: SLC9A4 c.1919G gt A, KIAA1109 c.2933T gt C and c. 4268_4269delCCinsTA, HoxB6 c.668C gt A, HoxD12 c.418G gt A, and NCK2 c.745_746delAAinsG, from which NCK2 c.745_746delAAinsG is novel. Data validation in pediatric celiac disease patients of Greek (n=109) and Serbian (n=73) descent and their healthy counterparts (n=111 and n=32, respectively) indicated that HoxD12 c.418G gt A is more prevalent in celiac disease patients in the Serbian population (P lt 0.01), while NCK2 c.745_746delAAinsG is less prevalent in celiac disease patients rather than healthy individuals of Greek descent (P = 0. 03). SLC9A4 c.1919G gt A and KIAA1109 c.2933T gt C and c.4268_4269delCCinsTA were more abundant in patients; nevertheless, they failed to show statistical significance. Conclusions: The next-generation sequencing-based family genomics approach described herein may serve as a paradigm towards the identification of novel functional variants with the aim of understanding complex disease pathobiology

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

Study of the genetic basis of celiac disease in greek patients: extensions in immunogenetics

Celiac disease is a complex chronic immune-mediated disorder of the small intestine. Today, the pathobiology of the disease is unclear, perplexing differential diagnosis, patient stratification, and decision-making in the clinic. Several genetic, epidemiological, clinical, serological, and pathophysiological data indicate that celiac disease is associated with autoimmune thyroid disorders and in particular, Graves’ disease. Today, no clear nomogram is effective to allow for optimum disease management and patient stratification. Herein, we adopted a next-generation sequencing approach in a celiac disease trio of Greek descent to identify all genomic variants with the potential of celiac disease predisposition. Additionally, we explored the role of selected genomic variants resulting from extensive data mining for overlapping susceptibility between Graves’ disease and paediatric coeliac disease aiming for an immunogenetic model towards the identification of coeliac disease patients with an increased risk of developing Graves’ disease.The multi-step next-generation sequencing-based family genomics approach revealed six genomic variants of prime interest: SLC9A4 c.1919G>A, KIAA1109 c.2933T>C and c. 4268_4269delCCinsTA, HoxB6 c.668C>A, HoxD12 c.418G>A, and NCK2 c.745_746delAAinsG, from which NCK2 c. 745_746delAAinsG is novel. Data validation in pediatric celiac disease patients of Greek (n = 109) and Serbian (n = 73) descent and their healthy counterparts (n = 111 and n = 32, respectively) indicated that HoxD12 c. 418G>A is more prevalent in celiac disease patients in the Serbian population (P A and KIAA1109 c.2933T>C and c.4268_4269delCCinsTA were more abundant in patients; nevertheless, they failed to show statistical significance.Moreover, extensive data mining, pathway analysis and literature review resulted in the selection of (CTLA4) c.*1421G>A, c.*1384G>A και c.49A>G, c. 49A>T, BACH2 c.-162+36253G>T και c.-274-41831G>C; c.-275+4001G> και IL23R c.956-8194A>G, c.956-819A>T. Data validation in pediatric celiac disease patients of Hellenic origin (n=109) and their ethnically matched counterparts (n=111) indicated that CTLA4 c.*1421G>A, c.*1384G>A is less prevalent in celiac disease patients rather than healthy individuals of Greek descent (P = 0. 01). CTLA4 c.49A>G, c. 49A>T and BACH2 c.-162+36253G>T and IL23R c.-274-41831G>C; c.956-8194A>G, c.956-819A>T were more abundant in patients and BACH2 c.-275+4001G> T was more prevalent in healthy individuals; nevertheless, they failed to show statistical significance.The immunogenomics approach described herein may serve as a paradigm towards the identification of novel functional variants for theranostics and comorbidity biomarker discovery aiming to dissect the genetic basis of pediatric celiac disease in patients of Hellenic origin. Such risk variants may serve as the building block of a nomogram to optimize Graves’ and Celiac disease management and patient stratification.Η κοιλιοκάκη είναι μια σύνθετη χρόνια ανοσοδιαμεσολαβούμενη διαταραχή του λεπτού εντέρου. Σήμερα, η παθοβιολογία της νόσου είναι ασαφής, προκαλεί σύγχυση στη διαφορική διάγνωση, τη στρωματοποίηση των ασθενών και τη λήψη αποφάσεων στην κλινική. Αρκετά γενετικά, επιδημιολογικά, κλινικά, ορολογικά και παθοφυσιολογικά δεδομένα υποδεικνύουν ότι η κοιλιοκάκη σχετίζεται με αυτοάνοσες διαταραχές του θυρεοειδούς και ειδικότερα με τη νόσο του Graves. Σήμερα, κανένα σαφές νομόγραμμα δεν είναι αποτελεσματικό για να επιτρέπει τη βέλτιστη διαχείριση της νόσου και τη στρωματοποίηση των ασθενών.Στην παρούσα έρευνα, εφαρμόσαμε μια προσέγγιση επόμενης γενιάς αλληλούχησης και ανάλυση τύπου trio σε μια οικογένεια ελληνικής καταγωγής για τον εντοπισμό γενετικών παραλλαγών/ βιοδεικτών προδιάθεσης για τη κοιλιοκάκη. Επιπλέον, διερευνήσαμε το ρόλο επιλεγμένων γενετικών παραλλαγών, που προέκυψαν από εκτεταμένη εξόρυξη δεδομένων για την αλληλεπικαλυπτόμενη ευαισθησία (συννοσηρότητα) της νόσου του Graves και της κοιλιοκάκης στην παιδική ηλικία, με στόχο ένα ανοσογενετικό μοντέλο για τη βέλτιστη διαστρωμάτωση ασθενών με κοιλιοκάκη και αυξημένο κίνδυνο ανάπτυξης της νόσου του Graves.Η προσέγγιση αλληλούχησης επόμενης γενιάς αποκάλυψε έξι γενωμικές παραλλαγές πρωταρχικού ενδιαφέροντος: SLC9A4 c.1919G>A, KIAA1109 c.2933T>C και c. 4268_4269delCCinsTA, HΟΧB6 c.668C>Α, HΟΧD12 c.418G>Α και NCK2 c.745_746delAAinsG, από τις οποίες η NCK2 c.745_746delAAinsG είναι καινοφανής. Η επικύρωση των δεδομένων σε ασθενείς με κοιλιοκάκη στην παιδική ηλικία ελληνικής (n = 109) και σερβικής (n = 73) καταγωγής και στους υγιείς ομολόγους τους (n = 111 και n = 32, αντίστοιχα) έδειξε ότι η HΟΧD12 c.418G>Α (P A και KIAA1109 c.2933T>C και c.4268_4269delCCinsTA ήταν πιο συχνές στους ασθενείς. Παρ 'όλα αυτά, δεν απέδειξαν στατιστική σημαντικότητα.Επιπλέον, η εκτεταμένη εξόρυξη δεδομένων και κειμένου, η ανάλυση των μοριακών μονοπατιών και η συστηματική ανασκόπηση της βιβλιογραφίας οδήγησαν στην επιλογή των CTLA4 c.*1421G>A, c.*1384G>A και c.49A>G, c. 49Α>Τ, BACH2 c.-162 + 36253G> Τ και c.-274-41831G> C; c.-275 + 4001G> και IL23R c.956-8194Α>G, c.956-819Α>Τ. Η επικύρωση των δεδομένων σε ασθενείς με κοιλιακή στην παιδική ηλικία ελληνικής καταγωγής (n = 109) και στους ομόλογούς τους (n = 111) έδειξε ότι η CTLA4 c.*1421G>A, c. *1384G>A είναι λιγότερο διαδεδομένη στους ασθενείς με κοιλιοκάκη έναντι των υγιών ατόμων (P = 0,01). Οι CTLA4 c.49A>G, c. 49Α>Τ, BACH2 c.-162 + 36253G> Τ και IL23R c.-274-41831G> C. c.956-8194A> G, c.956-819A> T ήταν πιο συχνές στους ασθενείς έναντι των υγιών ατόμων και η BACH2 c.-275 + 4001G>T ήταν πιο διαδεδομένη στα υγιή άτομα έναντι των παιδιατρικών ασθενών με κοιλιοκάκη. Εντούτοις, δεν απέδειξαν στατιστική σημασία.Η ανοσογονιδιωματική προσέγγιση που περιγράφεται στο παρόν πόνημα δύναται να αποτελέσει πρότυπο για την ταυτοποίηση νέων λειτουργικών παραλλαγών/ βιοδεικτών θερανοστικής και συννοσηρότητας, με σκοπό την αποσαφήνιση της γενετικής συνιστώσας της κοιλιοκάκης στην παιδική ηλικία στον ελληνικό πληθυσμό. Τέτοιες παραλλαγές κινδύνου μπορούν να χρησιμεύσουν ως δομικό στοιχείο ενός νομογράμματος για τη βελτιστοποίηση της διαχείρισης της κοιλιοκάκης και της νόσου του Graves και της στρωματοποίησης των ασθενών

Novel genetic risk variants for pediatric celiac disease

Background: Celiac disease is a complex chronic immune-mediated disorder of the small intestine. Today, the pathobiology of the disease is unclear, perplexing differential diagnosis, patient stratification, and decision-making in the clinic.Methods: Herein, we adopted a next-generation sequencing approach in a celiac disease trio of Greek descent to identify all genomic variants with the potential of celiac disease predisposition.Results: Analysis revealed six genomic variants of prime interest: SLC9A4 c.1919G>A, KIAA1109 c.2933T>C and c.4268_4269delCCinsTA, HoxB6 c.668C>A, HoxD12 c.418G>A, and NCK2 c.745_746delAAinsG, from which NCK2 c.745_746delAAinsG is novel. Data validation in pediatric celiac disease patients of Greek (n = 109) and Serbian (n = 73) descent and their healthy counterparts (n = 111 and n = 32, respectively) indicated that HoxD12 c.418G>A is more prevalent in celiac disease patients in the Serbian population (P A and KIAA1109 c.2933T>C and c.4268_4269delCCinsTA were more abundant in patients; nevertheless, they failed to show statistical significance.Conclusions: The next-generation sequencing-based family genomics approach described herein may serve as a paradigm towards the identification of novel functional variants with the aim of understanding complex disease pathobiology.peer-reviewe

Additional file 2: of Novel genetic risk variants for pediatric celiac disease

Regulome DB questioned a possible role of the variants of interest in terms of transcription factor binding sites, chromatin states, eQTLs, differentially methylated regions, validated functional SNPs and DNase sensitivity. All variants had minimum or no impact. (XLSX 3.62 mb

Additional file 1: of Novel genetic risk variants for pediatric celiac disease

A seven-member Greek family has been recruited (informed consents have been obtained), and a trio analysis (III-1, III-2, IV-3) has been performed using the celiac disease model. (PNG 136 kb