Genomic imprinting analyses identify maternal effects as a cause of phenotypic variability in type 1 diabetes and rheumatoid arthritis
Abstrakt
Imprinted genes, giving rise to parent-of-origin effects (POEs), have been hypothesised to affect type 1 diabetes (T1D) and rheumatoid arthritis (RA). However, maternal effects may also play a role.
By using a mixed model that is able to simultaneously consider all kinds of POEs, the importance of POEs for the development of T1D and RA was investigated in a variance components analysis. The analysis was based on Swedish population-scale pedigree data.
With P = 0.18 (T1D) and P = 0.26 (RA) imprinting variances were not significant. Explaining up to 19.00% (+/- 2.00%) and 15.00% (+/- 6.00%) of the phenotypic variance, the maternal environmental variance was significant for T1D (P = 1.60 x 10(-24)) and for RA (P = 0.02).
For the first time, the existence of maternal genetic effects on RA was indicated, contributing up to 16.00% (+/- 3.00%) of the total variance. Environmental factors such as the social economic index, the number of offspring, birth year as well as their interactions with sex showed large effects.