Dataset Information

PE-META-EUROPE_CENTRAL_ASIA-MATERNAL

ABSTRACT: Fixed effect meta-analysis summary statistics combining GWAS of maternal preeclampsia cases and controls from Europe (UK, Iceland, Norway, Denmark and Finland) and Central Asia (Kazakhstan and Uzbekistan).

PROVIDER: EGAD00010001988 | EGA |

REPOSITORIES: EGA

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Publications

Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women.

Steinthorsdottir Valgerdur V McGinnis Ralph R Williams Nicholas O NO Stefansdottir Lilja L Thorleifsson Gudmar G Shooter Scott S Fadista João J Sigurdsson Jon K JK Auro Kirsi M KM Berezina Galina G Borges Maria-Carolina MC Bumpstead Suzannah S Bybjerg-Grauholm Jonas J Colgiu Irina I Dolby Vivien A VA Dudbridge Frank F Engel Stephanie M SM Franklin Christopher S CS Frigge Michael L ML Frisbaek Yr Y Geirsson Reynir T RT Geller Frank F Gretarsdottir Solveig S Gudbjartsson Daniel F DF Harmon Quaker Q Hougaard David Michael DM Hegay Tatyana T Helgadottir Anna A Hjartardottir Sigrun S Jääskeläinen Tiina T Johannsdottir Hrefna H Jonsdottir Ingileif I Juliusdottir Thorhildur T Kalsheker Noor N Kasimov Abdumadjit A Kemp John P JP Kivinen Katja K Klungsøyr Kari K Lee Wai K WK Melbye Mads M Miedzybrodska Zosia Z Moffett Ashley A Najmutdinova Dilbar D Nishanova Firuza F Olafsdottir Thorunn T Perola Markus M Pipkin Fiona Broughton FB Poston Lucilla L Prescott Gordon G Saevarsdottir Saedis S Salimbayeva Damilya D Scaife Paula Juliet PJ Skotte Line L Staines-Urias Eleonora E Stefansson Olafur A OA Sørensen Karina Meden KM Thomsen Liv Cecilie Vestrheim LCV Tragante Vinicius V Trogstad Lill L Simpson Nigel A B NAB Aripova Tamara T Casas Juan P JP Dominiczak Anna F AF Walker James J JJ Thorsteinsdottir Unnur U Iversen Ann-Charlotte AC Feenstra Bjarke B Lawlor Deborah A DA Boyd Heather Allison HA Magnus Per P Laivuori Hannele H Zakhidova Nodira N Svyatova Gulnara G Stefansson Kari K Morgan Linda L

Nature communications 20201125 1

Preeclampsia is a serious complication of pregnancy, affecting both maternal and fetal health. In genome-wide association meta-analysis of European and Central Asian mothers, we identify sequence variants that associate with preeclampsia in the maternal genome at ZNF831/20q13 and FTO/16q12. These are previously established variants for blood pressure (BP) and the FTO variant has also been associated with body mass index (BMI). Further analysis of BP variants establishes that variants at MECOM/3q ...[more]

PMID: 33239696

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Project description:Hypertension in pregnancy is the leading cause of morbidity and mortality in pregnancy, affecting up to 10% of all gestations1. Hypertensive disorders of pregnancy include chronic hypertension, gestational hypertension, eclampsia and pre-eclampsia, all of which increase the risk of complications in both mothers and babies during gestation. Preeclampsia, in particular, is characterised by the new-onset of gestational hypertension in the presence of proteinuria or other organ damage. It affects 5-7% of pregnancies and causes approximately 76,000 maternal deaths and 500,000 foetal deaths worldwide each year2. The classification of preeclampsia has been evolving over the last decade. In 2013, American College of Obstetricians and Gynecologists (ACOG) and International Society for the Study of Hypertension in Pregnancy (ISSHP) in the absence of proteinuria included other symptoms/features including liver dysfunction, thrombocytopenia, cerebrovascular events or foetal growth restriction (FGR) in the diagnosis of preeclampsia 1,3,4. Despite the fact that preeclampsia is a multifactorial and heterogeneous disorder, it is now widely accepted that preeclampsia is stratified depending on the time of onset into: i) early-onset PE (EOPE) manifested before 34 weeks of gestation, and ii) late-onset PE (LOPE) manifested from 34 weeks of gestation. Although EOPE and LOPE share the same diagnostic criteria, these two phenotypes of preeclampsia lead to different outcomes. EOPE is commonly associated with FGR, abnormal uterine artery Doppler often leading to preterm birth and higher risk of post-pregnancy morbidities5,6. On the other hand, LOPE appears to be a less severe disorder, often with normal or slightly increased uterine resistance index and a low rate of FGR6,7. Distinct delineation between EOPE and LOPE is still not well understood, with most patients with preeclampsia presenting elements of both pathologies proposing a clinical spectrum for preeclampsia. The lack of untargeted discovery studies involving ‘omics’ analyses has impeded understanding of the molecular differences between these two phenotypes of preeclampsia. Notably, a study from 20058 utilised a proteomics approach using urine samples from a cohort of pregnant women with EOPE and healthy controls, however the differences between EOPE and LOPE were not elucidated. Another more recent bioinformatics study, identified overlapping pathogenic mechanisms between preeclampsia, hypertension and heart disease but could not stratify between EOPE and LOPE due to underreported of data related to individual phenotypes9. In this study, we conducted an unbiased, comprehensive proteomics investigation using plasma samples collected from patients with EOPE (n=17) and LOPE (n=11), compared with age- and BMI-matched normotensive controls (n=18). The use of plasma samples is able to better reflect the pathogenesis of EOPE and LOPE as systemic conditions centred by widespread endothelial dysfunction.

Dataset Information

PE-META-EUROPE_CENTRAL_ASIA-MATERNAL

Publications

Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women.

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