Journal article
Gene-Centric Analysis of Preeclampsia Identifies Maternal Association at PLEKHG1
Hypertension (Dallas, Tex. 1979), Vol.72(2), pp.408-416
08/2018
DOI: 10.1161/HYPERTENSIONAHA.117.10688
PMCID: PMC6043396
PMID: 29967039
Abstract
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
<10
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
gene (odds ratio, 1.40 [1.23-1.60];
=5.90×10
). The rs9478812 effect was even stronger in the subset of European cases with known early-onset preeclampsia (236 cases diagnosed <37 weeks, 1864 controls; odds ratio, 1.59 [1.27-1.98];
=4.01×10
).
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.
Details
- Title: Subtitle
- Gene-Centric Analysis of Preeclampsia Identifies Maternal Association at PLEKHG1
- Creators
- Kathryn J GrayVesela P Kovacheva - Department of Anesthesiology (V.P.K.)Hooman Mirzakhani - Brigham and Women's HospitalAndrew C Bjonnes - Broad InstituteBerta Almoguera - Children's Hospital of PhiladelphiaAndrew T DeWan - Department of Chronic Disease Epidemiology (A.T.D.)Elizabeth W Triche - Yale UniversityAudrey F Saftlas - University of IowaJosephine Hoh - Department of Environmental Health Sciences (J.H.)Dale L Bodian - Inova Health SystemElisabeth Klein - Inova Health SystemKathi C Huddleston - Inova Health SystemSue Ann Ingles - University of Southern CaliforniaCharles J Lockwood - University of South FloridaHakon Hakonarson - University of PennsylvaniaThomas F McElrath - Franklin & Marshall CollegeJeffrey C Murray - University of IowaMelissa L Wilson - University of Southern CaliforniaErrol R Norwitz - Tufts Medical CenterS Ananth Karumanchi - Beth Israel Deaconess Medical CenterBrian T Bateman - Brigham and Women's HospitalBrendan J Keating - University of PennsylvaniaRicha Saxena - Brigham and Women's Hospital
- Resource Type
- Journal article
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.72(2), pp.408-416
- DOI
- 10.1161/HYPERTENSIONAHA.117.10688
- PMID
- 29967039
- PMCID
- PMC6043396
- NLM abbreviation
- Hypertension
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Grant note
- F32 HD086948 / NICHD NIH HHS T32 HL007427 / NHLBI NIH HHS R01 HD032579 / NICHD NIH HHS K08 HD075831 / NICHD NIH HHS Howard Hughes Medical Institute R21 HD046624 / NICHD NIH HHS K12 HD051959 / NICHD NIH HHS
- Language
- English
- Date published
- 08/2018
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984363667802771
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