Risk of preeclampsia in patients with genetic predisposition to common medical conditions: a case-control study (original) (raw)
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Genetic Risk Factors Associated With Preeclampsia and Hypertensive Disorders of Pregnancy
JAMA Cardiology
ImportanceA genetic contribution to preeclampsia susceptibility has been established but is still incompletely understood.ObjectiveTo disentangle the underlying genetic architecture of preeclampsia and preeclampsia or other maternal hypertension during pregnancy with a genome-wide association study (GWAS) of hypertensive disorders of pregnancy.Design, Setting, and ParticipantsThis GWAS included meta-analyses in maternal preeclampsia and a combination phenotype encompassing maternal preeclampsia and preeclampsia or other maternal hypertensive disorders. Two overlapping phenotype groups were selected for examination, namely, preeclampsia and preeclampsia or other maternal hypertension during pregnancy. Data from the Finnish Genetics of Pre-eclampsia Consortium (FINNPEC, 1990-2011), Finnish FinnGen project (1964-2019), Estonian Biobank (1997-2019), and the previously published InterPregGen consortium GWAS were combined. Individuals with preeclampsia or other maternal hypertension durin...
Reproductive biomedicine online, 2017
Pre-eclampsia is a risk factor for later life vascular and metabolic diseases. This study postulates that this reflects a common genetic cause, and investigates whether the INSR rs2059806 single nucleotide polymorphism (SNP) (a risk factor for essential hypertension, type 2 diabetes and metabolic syndrome) is also associated with pre-eclampsia. The association of INSR rs2059806 with pre-eclampsia was tested in two cohorts - a Caucasian case control group (123 pre-eclamptic mother-father-baby trios and 1185 mother-father-baby trios from uncomplicated pregnancies) and an independent cohort of Sinhalese women (175 women with pre-eclampsia and 171 women with uncomplicated pregnancies). In the Caucasian cohort, the prevalence of the INSR rs2059806 AA genotype was greater among pre-eclamptic women compared with the uncomplicated pregnancies (12.7% versus 4.7%, OR[95%CI] = 3.1[1.6-5.8], P = 0.0003). In the Sinhalese cohort, maternal INSR rs2059806 AA genotype was greater among pre-eclampti...
OBJECTIVE: Preeclampsia is a complex genetic disease of pregnancy with a heterogenous presentation, unknown cause and potential severe outcomes for both mother and child. Preeclamptic women have increased risk for atherothrombotic cardiovascular disease. We aimed to identify heritabilities and phenotypic correlations of preeclampsia and related conditions in the Norwegian Preeclampsia Family Biobank. METHODS: By applying a variance components model, a total of 493 individuals (from 138 families with increased occurrence of preeclampsia) were classified according to 30 disease-related phenotypes. RESULTS: Of parous women, 75.7% (263/338) had experienced preeclampsia and 35.7% of women with and 22.4% without preeclampsia delivered children small for gestational age (SGA). We identified 11 phenotypes as heritable. The increased occurrence of preeclampsia was reflected by the presence [heritability (H2r) = 0.60)] and severity (H2r = 0.15) of preeclampsia and being born in a preeclamptic pregnancy (H2r = 0.25). Other heritable phenotypes identified included SGA (H2r = 0.40), chronic hypertension (H2r = 0.57), severity of atherothrombotic cardiovascular disease (H2r = 0.31), BMI (H2r = 0.60) and pulmonary disease (H2r = 0.91). The heritable phenotype preeclampsia overlapped with SGA (P = 0.03), whereas pulmonary disease was phenotypically correlated with atherothrombotic cardiovascular disease (P < 0.01), SGA (P = 0.02) and BMI (P = 0.02). CONCLUSION: This is the first study identifying the H2r of a range of health-related conditions in preeclamptic families. Our study demonstrates how refinement of phenotypes leads to better H2r estimation and the identification of a biological relationship between preeclampsia and related traits.
BMC pregnancy and childbirth, 2015
Preeclampsia is a major pregnancy complication without curative treatment available. A Norwegian Preeclampsia Family Cohort was established to provide a new resource for genetic and molecular studies aiming to improve the understanding of the complex pathophysiology of preeclampsia. Participants were recruited from five Norwegian hospitals after diagnoses of preeclampsia registered in the Medical birth registry of Norway were verified according to the study's inclusion criteria. Detailed obstetric information and information on personal and family disease history focusing on cardiovascular health was collected. At attendance anthropometric measurements were registered and blood samples were drawn. The software package SPSS 19.0 for Windows was used to compute descriptive statistics such as mean and SD. P-values were computed based on t-test statistics for normally distributed variables. Nonparametrical methods (chi square) were used for categorical variables. A cohort consisting...
Preeclampsia and cardiovascular disease share genetic risk factors on chromosome 2q22
Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health, 2014
Objective: Four putative single nucleotide polymorphism (SNP) risk variants at the preeclampsia susceptibility locus on chromosome 2q22; rs2322659 (LCT), rs35821928 (LRP1B), rs115015150 (RND3) and rs17783344 (GCA), were recently shown to associate with known cardiovascular risk factors in a Mexican American cohort. This study aimed to further evaluate the pleiotropic effects of these preeclampsia risk variants in an independent Australian population-based cohort. Methods: The four SNPs were genotyped in the Western Australian Pregnancy Cohort (Raine) Study that included DNA, clinical and biochemical data from 1,246 mothers and 1,404 of their now adolescent offspring. Genotype association analyses were undertaken using the SOLAR software. Results: Nominal associations (P < 0.05) with cardiovascular risk factors were detected for all four SNPs. The LCT SNP was associated with decreased maternal height (P = 0.005) and decreased blood glucose levels in adolescents (P = 0.022). The LRP1B SNP was associated with increased maternal height (P = 0.026) and decreased maternal weight (P = 0.044). The RND3 SNP was associated with decreased triglycerides in adolescents (P = 0.001). The GCA SNP was associated with lower risk in adolescents to be born of a preeclamptic pregnancy (P = 0.003) and having a mother with prior preeclamptic pregnancy (P = 0.033). Conclusions: Our collective findings support the hypothesis that genetic mechanisms for preeclampsia and CVD are, at least in part, shared, but need to be interpreted with some caution as a Bonferroni correction for multiple testing adjusted the statistical significance threshold (adjusted P < 0.001).
Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology, 2017
To summarize evidence from the literature on the risk factors associated with preeclampsia, assess the presence of statistical biases and identify associations with robust evidence. We searched PubMed and ISI Web of Science from inception to October, 2016, to identify systematic reviews and meta-analyses of observational studies examining associations between genetic and non-genetic risk factors for preeclampsia. For each meta-analysis we estimated the summary effect size by random-effects and fixed-effects models, the 95% confidence interval and the 95% prediction interval. We estimated the between-study heterogeneity expressed by I2 (considering above 75% as very large), evidence of small-study effects (large studies had significantly more conservative results than smaller studies and evidence of excess significance bias (too many studies with statistically significant results). Fifty-seven eligible papers were identified providing data on 130 associations including 1466 primary s...
Genetic Risk Score for Essential Hypertension and Risk of Preeclampsia
American journal of hypertension, 2015
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 (DB...
Genetic Predisposition to Dyslipidemia and Risk of Preeclampsia
American Journal of Hypertension, 2014
Preeclampsia is a multisystem disorder of pregnancy characterized by de novo hypertension and proteinuria with onset after 20 weeks gestation. 1 In the absence of proteinuria, de novo hypertension with new onset of any of the following will also qualify a woman for a diagnosis of preeclampsia: thrombocytopenia, renal insufficiency, impaired liver function, pulmonary edema, or cerebral/visual disturbances. Complicating approximately 3% of all deliveries in the United States, 3,4 preeclampsia is a leading cause of maternal and infant morbidity and mortality worldwide. 5,6 Without Background Large epidemiologic studies support the role of dyslipidemia in preeclampsia; however, the etiology of preeclampsia or whether dyslipidemia plays a causal role remains unclear. We examined the association between the genetic predisposition to dyslipidemia and risk of preeclampsia using validated genetic markers of dyslipidemia.