Ülegenoomne assotsiatsiooniuuring kubemesonga geneetiliste ...

9 Summary
Repair of inguinal hernia is one of the most common operations in general surgery. Thus
there are many methods of inguinal hernia repair, etiology of hernia formation still poorly
understood. The cause of inguinal hernia is multifactorial and previous studies provide
evidence for a genetic component of the disease. The aim of the present study has been
identifying genetic loci that can be associated with inguinal hernia in Estonian population.
In the present study 8 911 794 markers for 3851 were analysed for individuals from Estonia
population. The logistic regression method was used to analyse inguinal hernia data and
covariates sex and age were used. Markers were tested using an additive model.
In this study genome-wide statistical significant associations were not identified. Our results
suggest, that there are no genes with large effects to hernia but rather many genes all having
small relative risks. Additionally, the phenotype of disease is complex and the selection of
cases and controls can be suboptimal.
The associations with P-value less than 10 -5 revealed 35 loci containing 5 loci, which
potentially are novel candidate loci for inguinal hernia. These loci were near or within
HTRA3, NRG1, MFAP5, PDZRN3 and TBC1D19 gene regions. All this genes are
associated with collagen or extracellular matrix, which have been mentioned in previous
studies of inguinal hernia. In additional analysis, men were analysed separately. Both
analysis – men separately and all individuals, revealed the same locus, NRG1. Interestingly,
this gene is associated with collagen diassamble.
Even through present genome-wide association study didn’t identify statistically significant
results, several interesting novel loci were found for inguinal hernia. To validate the results,
a replication study must be considered using independent cohort data.
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