PMID- 38374560 OWN - NLM STAT- MEDLINE DCOM- 20240221 LR - 20240221 IS - 1536-4801 (Electronic) IS - 0277-2116 (Linking) VI - 78 IP - 2 DP - 2024 Feb TI - Genotypes predisposing for celiac disease and autoimmune diabetes and risk of infections in early childhood. PG - 295-303 LID - 10.1002/jpn3.12078 [doi] AB - OBJECTIVES: Infections in early childhood have been associated with risk of celiac disease (CD) and type 1 diabetes (T1D). We investigated whether this is driven by susceptibility genes for autoimmune disease by comparing infection frequency by genetic susceptibility variants for CD or T1D. METHODS: We genotyped 373 controls and 384 children who developed CD or T1D in the population-based Norwegian Mother, Father and Child Cohort study (MoBa) study for human leukocyte antigen (HLA)-DQ, FUT2, SH2B3, and PTPN22, and calculated a weighted non-HLA genetic risk score (GRS) for CD and T1D based on over 40 SNPs. Parents reported infections in questionnaires when children were 6 and 18 months old. We used negative binomial regression to estimate incidence rate ratio (IRR) for infections by genotype. RESULTS: HLA genotypes for CD and T1D or non-HLA GRS for T1D were not associated with infections. The non-HLA GRS for CD was associated with a nonsignificantly lower frequency of infections (aIRR: 0.95, 95% CI: 0.87-1.03 per weighted allele score), and significantly so when restricting to healthy controls (aIRR: 0.89, 0.81-0.99). Participants homozygous for rs601338(A;A) at FUT2, often referred to as nonsecretors, had a nonsignificantly lower risk of infections (aIRR: 0.91, 95% CI: 0.83-1.01). SH2B3 and PTPN22 genotypes were not associated with infections. The association between infections and risk of CD (OR: 1.15 per five infections) was strengthened after adjustment for HLA genotype and non-HLA GRS (OR: 1.24). CONCLUSIONS: HLA variants and non-HLA GRS conferring susceptibility for CD were not associated with increased risk of infections in early childhood and is unlikely to drive the observed association between infections and risk of CD or T1D in many studies. CI - (c) 2023 The Authors. Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. FAU - Stordal, Ketil AU - Stordal K AD - Department of Pediatric Research, Faculty of Medicine, University of Oslo, Oslo, Norway. AD - Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway. FAU - Tapia, German AU - Tapia G AD - Norwegian Institute of Public Health, Oslo, Norway. FAU - Lund-Blix, Nicolai A AU - Lund-Blix NA AD - Norwegian Institute of Public Health, Oslo, Norway. FAU - Stene, Lars C AU - Stene LC AD - Norwegian Institute of Public Health, Oslo, Norway. LA - eng PT - Journal Article DEP - 20231211 PL - United States TA - J Pediatr Gastroenterol Nutr JT - Journal of pediatric gastroenterology and nutrition JID - 8211545 RN - 0 (HLA-DQ Antigens) RN - EC 3.1.3.48 (PTPN22 protein, human) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 22) SB - IM MH - Child MH - Female MH - Humans MH - Child, Preschool MH - Infant MH - *Diabetes Mellitus, Type 1/complications/genetics MH - *Celiac Disease/complications MH - Cohort Studies MH - Genotype MH - Genetic Predisposition to Disease MH - HLA-DQ Antigens/genetics MH - Genetic Risk Score MH - Protein Tyrosine Phosphatase, Non-Receptor Type 22/genetics OTO - NOTNLM OT - HLA OT - celiac disease OT - gene OT - infection EDAT- 2024/02/20 11:50 MHDA- 2024/02/21 11:22 CRDT- 2024/02/20 00:19 PHST- 2023/09/28 00:00 [revised] PHST- 2023/06/28 00:00 [received] PHST- 2023/11/28 00:00 [accepted] PHST- 2024/02/21 11:22 [medline] PHST- 2024/02/20 11:50 [pubmed] PHST- 2024/02/20 00:19 [entrez] AID - 10.1002/jpn3.12078 [doi] PST - ppublish SO - J Pediatr Gastroenterol Nutr. 2024 Feb;78(2):295-303. doi: 10.1002/jpn3.12078. Epub 2023 Dec 11.