Gene-Centric Analysis of Preeclampsia Identifies Maternal Association at PLEKHG1
| Autor: | Thomas F. McElrath, Charles J. Lockwood, Brendan J. Keating, Melissa L. Wilson, Audrey F. Saftlas, Dale L. Bodian, Elizabeth W. Triche, Jeffrey C. Murray, Elisabeth Klein, Kathi Huddleston, Hakon Hakonarson, Hooman Mirzakhani, Josephine Hoh, Richa Saxena, Berta Almoguera, S. Ananth Karumanchi, Brian T. Bateman, Vesela P. Kovacheva, Kathryn J. Gray, Andrew Bjonnes, Errol R. Norwitz, Andrew T. DeWan, Sue A. Ingles |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Gestational hypertension medicine.medical_specialty education.field_of_study business.industry Population Case-control study Genome-wide association study Odds ratio medicine.disease Preeclampsia 03 medical and health sciences 030104 developmental biology Internal medicine Internal Medicine medicine Genetic predisposition education business Genetic association |
| Zdroj: | Hypertension. 72:408-416 |
| ISSN: | 1524-4563 0194-911X |
| DOI: | 10.1161/hypertensionaha.117.10688 |
| Popis: | The genetic susceptibility to preeclampsia, a pregnancy-specific complication with significant maternal and fetal morbidity, has been poorly characterized. To identify maternal genes associated with preeclampsia risk, we assembled 498 cases and 1864 controls of European ancestry from preeclampsia case-control collections in 5 different US sites (with additional matched population controls), genotyped samples on a cardiovascular gene-centric array composed of variants from ≈2000 genes selected based on prior genetic studies of cardiovascular and metabolic diseases and performed case-control genetic association analysis on 27 429 variants passing quality control. In silico replication testing of 9 lead signals with P − 4 was performed in independent European samples from the SOPHIA (Study of Pregnancy Hypertension in Iowa) and Inova cohorts (212 cases, 456 controls). Multiethnic assessment of lead signals was then performed in samples of black (26 cases, 136 controls), Hispanic (132 cases, 468 controls), and East Asian (9 cases, 80 controls) ancestry. Multiethnic meta-analysis (877 cases, 3004 controls) revealed a study-wide statistically significant association of the rs9478812 variant in the pleiotropic PLEKHG1 gene (odds ratio, 1.40 [1.23–1.60]; P meta =5.90×10 −7 ). The rs9478812 effect was even stronger in the subset of European cases with known early-onset preeclampsia (236 cases diagnosed P =4.01×10 −5 ). PLEKHG1 variants have previously been implicated in genome-wide association studies of blood pressure, body weight, and neurological disorders. Although larger studies are required to further define maternal preeclampsia heritability, this study identifies a novel maternal risk locus for further investigation. |
| Databáze: | OpenAIRE |
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