Preeclampsia does not share common risk alleles in 9p21 with coronary artery disease and type 2 diabetes.
Preeclampsia is a common and partially genetic pregnancy complication characterized by hypertension and proteinuria. Association with cardiovascular disease and type 2 diabetes has been reported in 9p21 by several genome-wide association studies. It has been hypothesized that cardiometabolic diseases may share common etiology with preeclampsia.



We tested association with the 9p21 region to preeclampsia in the Finnish population by genotyping 23 tagging single nucleotide polymorphisms (SNPs) in 15 extended preeclampsia families and in a nationwide cohort consisting of 281 cases and 349 matched controls. Replication was conducted in additional datasets.



Four SNPs (rs7044859, rs496892, rs564398 and rs7865618) showed nominal association (p ≤ 0.024 uncorrected) with preeclampsia in the case-control cohort. To increase power, we genotyped two SNPs in additional 388 cases and 341 controls from the Finnish Genetics of Preeclampsia Consortium (FINNPEC) cohort. Partial replication was also attempted in a UK cohort (237 cases and 199 controls) and in 74 preeclamptic families from Australia/New Zealand. We were unable to replicate the initial association in the extended Finnish dataset or in the two international cohorts.



Our study did not find evidence for the involvement of the 9p21 region in the risk of preeclampsia. Key Message Chromosome 9p21 is not associated with preeclampsia.
a Medical and Clinical Genetics , University of Helsinki and Helsinki University Hospital , Helsinki , Finland ;
Tea
T
Kaartokallio
a Medical and Clinical Genetics , University of Helsinki and Helsinki University Hospital , Helsinki , Finland ;|b Bacteriology and Immunology Department , University of Helsinki and Helsinki University Hospital , Helsinki , Finland ;|c Immunobiology Research Program, Research Programs Unit , University of Helsinki and Helsinki University Hospital , Helsinki , Finland ;
A Inkeri
AI
Lokki
d Department of Biosciences and Nutrition , Karolinska Institutet , Stockholm , Sweden ;
Hanna
H
Peterson
e Division of Cardiovascular Medicine, University of Cambridge , Cambridge , UK ;
Katja
K
Kivinen
f Finnish Red Cross Blood Service , Helsinki , Finland ;
Leena
L
Hiltunen
g Molecular Neurology Research Program, Research Programs Unit , University of Helsinki and Helsinki University Hospital , Helsinki , Finland ;|h Folkhälsan Institute of Genetics , Helsinki , Finland ;
Elina
E
Salmela
i New York Genome Center , New York City , NY , USA ;|j Department of Systems Biology , Columbia University , New York City , NY , USA ;
Tuuli
T
Lappalainen
k Institute of Biotechnology , University of Helsinki , Helsinki , Finland ;
Paula
P
Maanselkä
a Medical and Clinical Genetics , University of Helsinki and Helsinki University Hospital , Helsinki , Finland ;
Sanna
S
Heino
l Department of Pathology , University of Helsinki , Helsinki , Finland ;
Sakari
S
Knuutila
m Department of Medical Biochemistry, Faculty of Medicine , Assiut University , Assiut , Egypt ;|n School of Molecular Medical Sciences , University of Nottingham , Nottingham , UK ;
Ayat
A
Sayed
o Division of Women's Health , King's College London , London , UK ;
Lucilla
L
Poston
p Department of Maternal-Fetal Medicine , Pregnancy Research Centre and University of Melbourne's Department of Obstetrics and Gynaecology, Royal Women's Hospital , Parkville , Victoria , Australia ;
Shaun P
SP
Brennecke
q South Texas Diabetes and Obesity Institute, School of Medicine , University of Texas Rio Grande Valley , Brownsville , TX , USA ;
Matthew P
MP
Johnson
r School of Life Sciences , University of Nottingham , Nottingham , UK ;
Linda
L
Morgan
s Faculty of Medicine Dentistry and Health Sciences , The University of Western Australia , Perth , Australia ;|t School of Biomedical Sciences , Faculty of Health Science, Curtin University , Perth , Australia ;|u Centre for Genetic Origins of Health and Disease, Medical Research Foundation , Royal Perth Hospital , Perth , Australia ;
Eric K
EK
Moses
d Department of Biosciences and Nutrition , Karolinska Institutet , Stockholm , Sweden ;|g Molecular Neurology Research Program, Research Programs Unit , University of Helsinki and Helsinki University Hospital , Helsinki , Finland ;|h Folkhälsan Institute of Genetics , Helsinki , Finland ;
Juha
J
Kere
a Medical and Clinical Genetics , University of Helsinki and Helsinki University Hospital , Helsinki , Finland ;|v Institute for Molecular Medicine Finland , University of Helsinki , Helsinki , Finland.
Hannele
H
Laivuori
D001315:Australia; D016022:Case-Control Studies; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D003324:Coronary Artery Disease / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D009520:New Zealand; D020641:Polymorphism, Single Nucleotide; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy; D006113:United Kingdom
CAD; Preeclampsia; case-control study; chromosome 9