title: Genetic architecture differences between pediatric and adult-onset inflammatory bowel diseases in the Polish population.
abstract: Most inflammatory bowel diseases (IBDs) are classic complex disorders represented by common alleles. Here we aimed to define the genetic architecture of pediatric and adult-onset IBDs for the Polish population. A total of 1495 patients were recruited, including 761 patients with Crohn's disease (CD; 424 pediatric), 734 patients with ulcerative colitis (UC; 390 pediatric), and 934 healthy controls. Allelotyping employed a pooled-DNA genome-wide association study (GWAS) and was validated by individual genotyping. Whole exome sequencing (WES) was performed on 44 IBD patients diagnosed before 6 years of age, 45 patients diagnosed after 40 years of age, and 18 healthy controls. Altogether, out of 88 selected SNPs, 31 SNPs were replicated for association with IBD. A novel BRD2 (rs1049526) association reached significance of P = 5.2 × 10-11and odds ratio (OR) = 2.43. Twenty SNPs were shared between pediatric and adult patients; 1 and 7 were unique to adult-onset and pediatric-onset IBD, respectively. WES identified numerous rare and potentially deleterious variants in IBD-associated or innate immunity-associated genes. Deleterious alleles in both groups were over-represented among rare variants in affected children. Our GWAS revealed differences in the polygenic architecture of pediatric- and adult-onset IBD. A significant accumulation of rare and deleterious variants in affected children suggests a contribution by yet unexplained genetic components.
authors.affiliation: Department of Gastroenterology and Hepatology, Medical Center for Postgraduate Education, Warsaw 01-813, Poland.|Department of Genetics, Cancer Center-Institute, Warsaw 02-781, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Ostrowski
authors.affiliation: Department of Gastroenterology and Hepatology, Medical Center for Postgraduate Education, Warsaw 01-813, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Paziewska
authors.affiliation: Department of Pediatric Gastroenterology and Nutrition, Medical University of Warsaw, Warsaw 02-091, Poland.
authors.forename: Izabella
authors.initials: I
authors.lastname: Lazowska
authors.affiliation: Department of Gastroenterology and Hepatology, Medical Center for Postgraduate Education, Warsaw 01-813, Poland.
authors.forename: Filip
authors.initials: F
authors.lastname: Ambrozkiewicz
authors.affiliation: Department of Genetics, Cancer Center-Institute, Warsaw 02-781, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Goryca
authors.affiliation: Department of Gastroenterology and Hepatology, Medical Center for Postgraduate Education, Warsaw 01-813, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Kulecka
authors.affiliation: Department of Gastroenterology and Hepatology, Medical Center for Postgraduate Education, Warsaw 01-813, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Rawa
authors.affiliation: Department of Genetics, Cancer Center-Institute, Warsaw 02-781, Poland.
authors.forename: Jakub
authors.initials: J
authors.lastname: Karczmarski
authors.affiliation: Department of Genetics, Cancer Center-Institute, Warsaw 02-781, Poland.
authors.forename: Michalina
authors.initials: M
authors.lastname: Dabrowska
authors.affiliation: Department of Gastroenterology and Hepatology, Medical Center for Postgraduate Education, Warsaw 01-813, Poland.
authors.forename: Natalia
authors.initials: N
authors.lastname: Zeber-Lubecka
authors.affiliation: Department of Gastroenterology and Hepatology, Medical Center for Postgraduate Education, Warsaw 01-813, Poland.
authors.forename: Roman
authors.initials: R
authors.lastname: Tomecki
authors.affiliation: Department of Genetics, Cancer Center-Institute, Warsaw 02-781, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Kluska
authors.affiliation: Department of Genetics, Cancer Center-Institute, Warsaw 02-781, Poland.
authors.forename: Aneta
authors.initials: A
authors.lastname: Balabas
authors.affiliation: Department of Genetics, Cancer Center-Institute, Warsaw 02-781, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Piatkowska
authors.affiliation: Department of Genetics, Cancer Center-Institute, Warsaw 02-781, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Paczkowska
authors.affiliation: Department of Gastroenterology, Hepatology and Feeding Disorders, Children's Memorial Health Institute, Warsaw 04-730, Poland.
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Kierkus
authors.affiliation: Department of Gastroenterology, Hepatology and Feeding Disorders, Children's Memorial Health Institute, Warsaw 04-730, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Socha
authors.affiliation: Department of Internal Medicine and Gastroenterology with IBD Subdivision, Central Clinical Hospital of the Ministry of the Interior, Warsaw 02-507, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Lodyga
authors.affiliation: Department of Internal Medicine and Gastroenterology with IBD Subdivision, Central Clinical Hospital of the Ministry of the Interior, Warsaw 02-507, Poland.|Faculty of Health Sciences, Jan Kochanowski University, Kielce 25-369, Poland.
authors.forename: Grazyna
authors.initials: G
authors.lastname: Rydzewska
authors.affiliation: Vascular Diseases and Internal Medicine, Nicolaus Copernicus University in Torun, Collegium Medicum, Bydgoszcz 85-067, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Klopocka
authors.affiliation: Vascular Diseases and Internal Medicine, Nicolaus Copernicus University in Torun, Collegium Medicum, Bydgoszcz 85-067, Poland.
authors.forename: Grazyna
authors.initials: G
authors.lastname: Mierzwa
authors.affiliation: Department of Pediatrics, Gastroenterology and Nutrition, Wroclaw Medical University, Wroclaw 50-367, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Iwanczak
authors.affiliation: Department of Pediatrics, Gastroenterology and Nutrition, Wroclaw Medical University, Wroclaw 50-367, Poland.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Krzesiek
authors.affiliation: Department of Pediatrics, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice 40-752 Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Bak-Drabik
authors.affiliation: Department of Pediatric Gastroenterology &Metabolic Diseases, Poznan University of Medical Sciences, Poznan 61-701, Poland.
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Walkowiak
authors.affiliation: Department of Pediatric Gastroenterology &Metabolic Diseases, Poznan University of Medical Sciences, Poznan 61-701, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Klincewicz
authors.affiliation: Department of Gastroenterology, Medical University of Lublin, Lublin 20-059, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Radwan
authors.affiliation: Department of Pediatrics, School of Medicine in Katowice, Medical University of Silesia, Katowice 40-752, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Grzybowska-Chlebowczyk
authors.affiliation: Department of Pediatrics, Pediatric Gastroenterology, Hepatology and Nutrition, Medical University of Gdansk, Gdansk 80-210, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Landowski
authors.affiliation: Department of Pediatrics, Pediatric Gastroenterology, Hepatology and Nutrition, Medical University of Gdansk, Gdansk 80-210, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Jankowska
authors.affiliation: Medical College, University of Rzeszow, Rzeszow 35-959, Poland.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Korczowski
authors.affiliation: Department of Gastroenterology, Pomeranian Medical University, Szczecin 70-204, Poland.
authors.forename: Teresa
authors.initials: T
authors.lastname: Starzynska
authors.affiliation: Department of Pediatric Gastroenterology and Nutrition, Medical University of Warsaw, Warsaw 02-091, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Albrecht
authors.affiliation: Department of Genetics, Cancer Center-Institute, Warsaw 02-781, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Mikula
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D008297:Male; D011044:Poland; D020641:Polymorphism, Single Nucleotide