Limited evidence for parent-of-origin effects in inflammatory bowel disease associated loci

Karin Fransen (Avtor), Mitja Mitrovič (Avtor), Uroš Potočnik (Avtor)

Povzetek

Background Genome-wide association studies of two main forms of inflammatory bowel diseases (IBD), Crohnʼs disease (CD) and ulcerative colitis (UC), have identified 99 susceptibility loci, but these explain only ~23% of the genetic risk. Part of the Žhidden heritabilityʼ could be in transmissible genetic effects in which mRNA expression in the offspring depends on the parental origin of the allele (genomic imprinting), since children whose mothers have CD are more often affected than children with affected fathers. We analyzed parent-of-origin (POO) effects in Dutch and Indian cohorts of IBD patients. Methods We selected 28 genetic loci associated with both CD and UC, and testedthem for POO effects in 181 Dutch IBD case-parent trios. Three susceptibility variants in NOD2 were tested in 111 CD trios and a significant finding was re-evaluated in 598 German trios. The UC-associated gene, BTNL2, reportedly imprinted, was tested in 70 Dutch UC trios. Finally, we used 62 independent Indian UC trios to test POO effects of five established Indian UC risk loci. Results We identified POO effects for NOD2 (L1007fs; OR = 21.0, P-value = 0.013) for CD; these results could not be replicated in an independent cohort (OR = 0.97, P-value = 0.95). A POO effect in IBD was observed for IL12B (OR = 3.2, P-value = 0.019) and PRDM1 (OR = 5.6, P-value = 0.04). In the Indian trios the IL10 locus showed a POO effect (OR = 0.2, P-value = 0.03). Conclusions Little is known about the effect of genomic imprinting in complex diseases such as IBD. We present limited evidence for POO effects for the tested IBD loci. POO effects explain part of the hidden heritability for complex genetic diseases but need to be investigated further.

Ključne besede

inflammatory bowel diseases;IBD;genetic locus;genetics;

Podatki

Jezik:	Angleški jezik
Leto izida:	2012
Tipologija:	1.01 - Izvirni znanstveni članek
Organizacija:	UM MF - Medicinska fakulteta
UDK:	616.34-002
COBISS:	512221240
ISSN:	1932-6203
Št. ogledov:	1059
Št. prenosov:	318
Ocena:	0 (0 glasov)
Metapodatki:

Ostali podatki

Sekundarni jezik:	Slovenski jezik
Sekundarne ključne besede:	Inflammatory Bowel Diseases;genetics;Vnetne črevesne bolezni;Genetika;
URN:	URN:SI:UM:
Vrsta dela (COBISS):	Znanstveno delo
Strani:	str. 1-8, e45287
Letnik:	ǂVol. ǂ7
Zvezek:	ǂiss. ǂ9
Čas izdaje:	2012
DOI:	10.1371/journal.pone.0045287
ID:	1439878