Whole-exome sequencing in multiplex preeclampsia families identifies novel candidate susceptibility genes
| Autor: | Juan M. Peralta, Phillip E. Melton, Dnyanada Gokhale-Agashe, Amir Ariff, Shaun P. Brennecke, Lawrence J. Abraham, Matthew P. Johnson, Alexander J. Rea, Eric K. Moses, John Blangero, Richard J.N. Allcock, Tegan J. McNab, Gemma Cadby |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Physiology Mutation Missense Genome-wide association study Single-nucleotide polymorphism 030204 cardiovascular system & hematology Receptors G-Protein-Coupled 03 medical and health sciences 0302 clinical medicine Gene Frequency Pre-Eclampsia Missing heritability problem Pregnancy Exome Sequencing Internal Medicine Medicine Humans Genetic Predisposition to Disease 030212 general & internal medicine Genetic Testing Annexin A5 Exome sequencing Genetic association Genetics business.industry Exons Neoplasm Proteins Pedigree Minor allele frequency Chromosome 1 open reading frame 35 Phenotype Female Cardiology and Cardiovascular Medicine business Imputation (genetics) Genome-Wide Association Study |
| Zdroj: | Journal of hypertension. 37(5) |
| ISSN: | 1473-5598 |
| Popis: | OBJECTIVE: Preeclampsia is a common and serious heritable disorder of human pregnancy. Although there have been notable successes in identification of maternal susceptibility genes a large proportion of the heritability of preeclampsia remains unaccounted for. It is has been postulated that rare variation may account for some of this missing heritability. In this study, we performed whole-exome sequencing (WES) in multiplex families to identify rare exonic risk variants. METHODS: We conducted WES in 244 individuals from 34 Australian/New Zealand multiplex preeclampsia families. Variants were tested for association with preeclampsia using a threshold model and logistic regression. RESULTS: We found significant association for two moderately rare missense variants, rs145743393 (Padj = 0.0032, minor allele frequency = 0.016) in the chromosome 1 open reading frame 35 (C1orf35) gene, and rs34270076 (Padj = 0.0128, minor allele frequency = 0.024) in the pyroglutamylated RFamide peptide receptor (QRFPR) gene. To replicate these associations we performed imputation in our Australian genome wide association scan for preeclampsia and found no significant exonic variants in either C1orf35 or QRFPR. However, 11 variants demonstrating nominal significance (P |
| Databáze: | OpenAIRE |
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