Novel genetic risk variants for pediatric celiac disease.
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.



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.



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 < 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>A and KIAA1109 c.2933T>C and c.4268_4269delCCinsTA were more abundant in patients; nevertheless, they failed to show statistical significance.



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.
Department of Pharmacy, School of Health Sciences, University of Patras, University Campus, Rion, 265 04, Patras, Greece.
Angeliki
A
Balasopoulou
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
Biljana
B
Stanković
Department of Pharmacy, School of Health Sciences, University of Patras, University Campus, Rion, 265 04, Patras, Greece.
Angeliki
A
Panagiotara
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
Gordana
G
Nikčevic
Complete Genomics Inc., Mountain View, CA, USA.|BGI Shenzhen, Shenzhen, 51803, China.
Brock A
BA
Peters
Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
Anne
A
John
Department of Pharmacy, School of Health Sciences, University of Patras, University Campus, Rion, 265 04, Patras, Greece.
Effrosyni
E
Mendrinou
Department of Pharmacy, School of Health Sciences, University of Patras, University Campus, Rion, 265 04, Patras, Greece.
Apostolos
A
Stratopoulos
Department of Pharmacy, School of Health Sciences, University of Patras, University Campus, Rion, 265 04, Patras, Greece.
Aigli Ioanna
AI
Legaki
Department of Pharmacy, School of Health Sciences, University of Patras, University Campus, Rion, 265 04, Patras, Greece.
Vasiliki
V
Stathakopoulou
Department of Pharmacy, School of Health Sciences, University of Patras, University Campus, Rion, 265 04, Patras, Greece.
Aristoniki
A
Tsolia
Department of Pharmacy, School of Health Sciences, University of Patras, University Campus, Rion, 265 04, Patras, Greece.
Nikolaos
N
Govaris
Department of Pharmacy, School of Health Sciences, University of Patras, University Campus, Rion, 265 04, Patras, Greece.
Sofia
S
Govari
Department of Pharmacy, School of Health Sciences, University of Patras, University Campus, Rion, 265 04, Patras, Greece.
Zoi
Z
Zagoriti
Department of Pharmacy, School of Health Sciences, University of Patras, University Campus, Rion, 265 04, Patras, Greece.
Konstantinos
K
Poulas
Department of Immunology and Histocompatibility, "Aghia Sophia" Children's Hospital, Athens, Greece.
Maria
M
Kanariou
Department of Immunology and Histocompatibility, "Aghia Sophia" Children's Hospital, Athens, Greece.
Nikki
N
Constantinidou
First Department of Pediatrics, National and Kapodistrian University of Athens Medical School, Athens, Greece.
Maro
M
Krini
Department of Immunology and Histocompatibility, "Aghia Sophia" Children's Hospital, Athens, Greece.
Kleopatra
K
Spanou
Department of Gastroenterology and Nutrition, University Children's Hospital, Medical Faculty, University of Belgrade, Belgrade, Serbia.
Nedeljko
N
Radlovic
Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
Bassam R
BR
Ali
Department of Applied Biomedical Science, Faculty of Health Sciences, University of Malta, Msida, Malta.
Joseph
J
Borg
Complete Genomics Inc., Mountain View, CA, USA.|BGI Shenzhen, Shenzhen, 51803, China.
Radoje
R
Drmanac
First Department of Pediatrics, National and Kapodistrian University of Athens Medical School, Athens, Greece.
George
G
Chrousos
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
Sonja
S
Pavlovic
First Department of Pediatrics, National and Kapodistrian University of Athens Medical School, Athens, Greece.
Eleftheria
E
Roma
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
Branka
B
Zukic
Department of Pharmacy, School of Health Sciences, University of Patras, University Campus, Rion, 265 04, Patras, Greece.|Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
George P
GP
Patrinos
Department of Pharmacy, School of Health Sciences, University of Patras, University Campus, Rion, 265 04, Patras, Greece. thkatsila@upatras.gr.
Theodora
T
Katsila
D001665:Binding Sites; D002446:Celiac Disease / Q000235:genetics*; D002648:Child; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
Celiac disease; Disease predisposition; Family genomics; Genomic variants; Next-generation sequencing