Genetic Risk Score for Essential Hypertension and Risk of Preeclampsia

Caitlin J Smith; Audrey F Saftlas; Cassandra N Spracklen; Elizabeth W Triche; Andrew Bjonnes; Brendan Keating; Richa Saxena; Patrick J Breheny; Andrew T Dewan; Jennifer G Robinson; Josephine Hoh; Kelli K Ryckman

doi:10.1093/ajh/hpv069

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Genetic Risk Score for Essential Hypertension and Risk of Preeclampsia

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Genetic Risk Score for Essential Hypertension and Risk of Preeclampsia

Caitlin J Smith, Audrey F Saftlas, Cassandra N Spracklen, Elizabeth W Triche, Andrew Bjonnes, Brendan Keating, Richa Saxena, Patrick J Breheny, Andrew T Dewan, Jennifer G Robinson, …

American journal of hypertension, Vol.29(1), pp.17-24

01/2016

DOI: 10.1093/ajh/hpv069

PMCID: PMC4692983

PMID: 26002928

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Abstract

Preeclampsia is a hypertensive complication of pregnancy characterized by novel onset of hypertension after 20 weeks gestation, accompanied by proteinuria. Epidemiological evidence suggests that genetic susceptibility exists for preeclampsia; however, whether preeclampsia is the result of underlying genetic risk for essential hypertension has yet to be investigated. Based on the hypertensive state that is characteristic of preeclampsia, we aimed to determine if established genetic risk scores (GRSs) for hypertension and blood pressure are associated with preeclampsia. Subjects consisted of 162 preeclamptic cases and 108 normotensive pregnant controls, all of Iowa residence. Subjects' DNA was extracted from buccal swab samples and genotyped on the Affymetrix Genome-wide Human SNP Array 6.0 (Affymetrix, Santa Clara, CA). Missing genotypes were imputed using MaCH and Minimac software. GRSs were calculated for hypertension, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) using established genetic risk loci for each outcome. Regression analyses were performed to determine the association between GRS and risk of preeclampsia. These analyses were replicated in an independent US population of 516 cases and 1,097 controls of European ancestry. GRSs for hypertension, SBP, DBP, and MAP were not significantly associated with risk for preeclampsia (P > 0.189). The results of the replication analysis also yielded nonsignificant associations. GRSs for hypertension and blood pressure are not associated with preeclampsia, suggesting that an underlying predisposition to essential hypertension is not on the causal pathway of preeclampsia.

Pre-Eclampsia - genetics

Pre-Eclampsia - epidemiology

United States - epidemiology

Genetic Predisposition to Disease

Follow-Up Studies

Risk Assessment

Humans

Risk Factors

Genotype

Pre-Eclampsia - etiology

Hypertension - physiopathology

Incidence

Pregnancy

Time Factors

Hypertension - complications

Female

Blood Pressure - physiology

Retrospective Studies

Hypertension - epidemiology

Essential Hypertension

Blood Pressure Determination

Details

Title: Subtitle: Genetic Risk Score for Essential Hypertension and Risk of Preeclampsia
Creators: Caitlin J Smith - Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa, USA
Audrey F Saftlas - Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa, USA
Cassandra N Spracklen - Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa, USA; Department of Genetics, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA
Elizabeth W Triche - Department of Epidemiology, School of Public Health, Brown University, Providence, Rhode Island, USA
Andrew Bjonnes - Center for Human Genetic Research and Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA
Brendan Keating - Department of Surgery, Penn Transplant Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
Richa Saxena - Center for Human Genetic Research and Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA
Patrick J Breheny - Department of Biostatistics, University of Iowa College of Public Health, Iowa City, Iowa, USA
Andrew T Dewan - Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, USA
Jennifer G Robinson - Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa, USA
Josephine Hoh - Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut, USA
Kelli K Ryckman - Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa, USA; kelli-ryckman@uiowa.edu
Resource Type: Journal article
Publication Details: American journal of hypertension, Vol.29(1), pp.17-24
DOI: 10.1093/ajh/hpv069
PMID: 26002928
PMCID: PMC4692983
NLM abbreviation: Am J Hypertens
ISSN: 0895-7061
eISSN: 1879-1905
Publisher: United States
Grant note: R01 HD032579 / NICHD NIH HHS R01 HD32579 / NICHD NIH HHS
Language: English
Date published: 01/2016
Academic Unit: Stead Family Department of Pediatrics; Epidemiology; Biostatistics; Internal Medicine
Record Identifier: 9983995175302771

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