NKG2D gene variation and susceptibility to viral bronchiolitis in childhood
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NKG2D gene variation and susceptibility to viral bronchiolitis in childhood. / Pasanen, Anu; Karjalainen, Minna K; Kummola, Laura; Waage, Johannes; Bønnelykke, Klaus; Ruotsalainen, Marja; Piippo-Savolainen, Eija; Goksör, Emma; Nuolivirta, Kirsi; Chawes, Bo; Vissing, Nadja; Bisgaard, Hans; Jartti, Tuomas; Wennergren, Göran; Junttila, Ilkka; Hallman, Mikko; Korppi, Matti; Rämet, Mika.
I: Pediatric Research, Bind 84, 2018, s. 451-457.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - NKG2D gene variation and susceptibility to viral bronchiolitis in childhood
AU - Pasanen, Anu
AU - Karjalainen, Minna K
AU - Kummola, Laura
AU - Waage, Johannes
AU - Bønnelykke, Klaus
AU - Ruotsalainen, Marja
AU - Piippo-Savolainen, Eija
AU - Goksör, Emma
AU - Nuolivirta, Kirsi
AU - Chawes, Bo
AU - Vissing, Nadja
AU - Bisgaard, Hans
AU - Jartti, Tuomas
AU - Wennergren, Göran
AU - Junttila, Ilkka
AU - Hallman, Mikko
AU - Korppi, Matti
AU - Rämet, Mika
PY - 2018
Y1 - 2018
N2 - BACKGROUND: Genetic factors associated with bronchiolitis are inadequately characterized. We therefore inspected a selected subpopulation of our previous genome-wide association study (GWAS) of bronchiolitis for overlap with known quantitative trait loci (QTLs) to identify susceptibility loci that potentially affect mRNA and protein levels.METHODS: GWAS included a Finnish-Swedish case-control population (n = 187), matched for age and site. We integrated GWAS variants (p < 10-4) with QTL data. We subsequently verified allele-specific expression of identified QTLs by flow cytometry. Association of the resulting candidate loci with bronchiolitis was tested in three additional cohorts from Finland and Denmark (n = 1201).RESULTS: Bronchiolitis-susceptibility variant rs10772271 resided within QTLs previously associated with NKG2D (NK group 2, member D) mRNA and protein levels. Flow cytometric analysis confirmed the association with protein level in NK cells. The GWAS susceptibility allele (A) of rs10772271 (odds ratio [OR] = 2.34) corresponded with decreased NKG2D expression. The allele was nominally associated with bronchiolitis in one Finnish replicate (OR = 1.50), and the other showed directional consistency (OR = 1.43). No association was detected in Danish population CONCLUSIONS: The bronchiolitis GWAS susceptibility allele was linked to decreased NKG2D expression in the QTL data and in our expression analysis. We propose that reduced NKG2D expression predisposes infants to severe bronchiolitis.
AB - BACKGROUND: Genetic factors associated with bronchiolitis are inadequately characterized. We therefore inspected a selected subpopulation of our previous genome-wide association study (GWAS) of bronchiolitis for overlap with known quantitative trait loci (QTLs) to identify susceptibility loci that potentially affect mRNA and protein levels.METHODS: GWAS included a Finnish-Swedish case-control population (n = 187), matched for age and site. We integrated GWAS variants (p < 10-4) with QTL data. We subsequently verified allele-specific expression of identified QTLs by flow cytometry. Association of the resulting candidate loci with bronchiolitis was tested in three additional cohorts from Finland and Denmark (n = 1201).RESULTS: Bronchiolitis-susceptibility variant rs10772271 resided within QTLs previously associated with NKG2D (NK group 2, member D) mRNA and protein levels. Flow cytometric analysis confirmed the association with protein level in NK cells. The GWAS susceptibility allele (A) of rs10772271 (odds ratio [OR] = 2.34) corresponded with decreased NKG2D expression. The allele was nominally associated with bronchiolitis in one Finnish replicate (OR = 1.50), and the other showed directional consistency (OR = 1.43). No association was detected in Danish population CONCLUSIONS: The bronchiolitis GWAS susceptibility allele was linked to decreased NKG2D expression in the QTL data and in our expression analysis. We propose that reduced NKG2D expression predisposes infants to severe bronchiolitis.
U2 - 10.1038/s41390-018-0086-9
DO - 10.1038/s41390-018-0086-9
M3 - Journal article
C2 - 29967528
VL - 84
SP - 451
EP - 457
JO - Pediatric Research
JF - Pediatric Research
SN - 0031-3998
ER -
ID: 216565853