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Genome-wide association analysis of early onset preeclampsia
Abstract Number: F-68
Abstract Type: Original Research
Introduction: Despite a strong heritable component, there are no genetic variants that have been robustly associated with preeclampsia. In an effort to shed light on the genetic basis for preeclampsia requiring delivery before 37 weeks, we performed an unbiased genome-wide association study in two populations of European ancestry.
Methods: We employed a case-control design using samples from preeclamptic patients and control women drawn from the same clinical sites as cases in US (290 cases and 786 controls) and in Finland (95 cases and 95 controls). Subjects were genotyped using a genome-wide SNP array containing 588,454 SNPs.
Single-SNP genetic association testing was completed using logistic regression, assuming additive effects for each risk allele present, and included principal components in the model to account for population structure. Statistical significance was judged at genome-wide significance threshold of p=5 x 10-8 to account for multiple testing.
Results: Interim analysis revealed suggestive association signals (p<10-4), including variants with consistent effects in both datasets in a non-coding RNA gene LINC01580 (OR=2.52 (95%CI 1.67-3.82) p=9.8x10-6 in Finnish samples, OR=1.18 (95% CI 0.97-1.43) p=0.097 in US samples. Association of a coding variant in lymphoid specific transcription factor ELF1 (OR=0.19 (95%CI 0.08-0.47) p=7.7x10-5) was also observed in Finnish samples, with the same signal conferring risk in previously reported GWAS of Crohn’s disease and SLE.
Conclusion: GWAS in two early onset preeclampsia populations preliminarily identify suggestive association signals that may offer biological insights into the basis of preeclampsia. These signals need to be replicated in an independent population.