Tea Kaartokallio1, A Inkeri Lokki1,2,3, Hanna Peterson4, Katja Kivinen5, Leena Hiltunen6, Elina Salmela7,8, Tuuli Lappalainen9,10, Paula Maanselkä11, Sanna Heino1, Sakari Knuutila12, Ayat Sayed13,14, Lucilla Poston15, Shaun P Brennecke16, Matthew P Johnson17, Linda Morgan18, Eric K Moses19,20,21, Juha Kere4,7,8, Hannele Laivuori1,22. 1. a Medical and Clinical Genetics , University of Helsinki and Helsinki University Hospital , Helsinki , Finland ; 2. b Bacteriology and Immunology Department , University of Helsinki and Helsinki University Hospital , Helsinki , Finland ; 3. c Immunobiology Research Program, Research Programs Unit , University of Helsinki and Helsinki University Hospital , Helsinki , Finland ; 4. d Department of Biosciences and Nutrition , Karolinska Institutet , Stockholm , Sweden ; 5. e Division of Cardiovascular Medicine, University of Cambridge , Cambridge , UK ; 6. f Finnish Red Cross Blood Service , Helsinki , Finland ; 7. g Molecular Neurology Research Program, Research Programs Unit , University of Helsinki and Helsinki University Hospital , Helsinki , Finland ; 8. h Folkhälsan Institute of Genetics , Helsinki , Finland ; 9. i New York Genome Center , New York City , NY , USA ; 10. j Department of Systems Biology , Columbia University , New York City , NY , USA ; 11. k Institute of Biotechnology , University of Helsinki , Helsinki , Finland ; 12. l Department of Pathology , University of Helsinki , Helsinki , Finland ; 13. m Department of Medical Biochemistry, Faculty of Medicine , Assiut University , Assiut , Egypt ; 14. n School of Molecular Medical Sciences , University of Nottingham , Nottingham , UK ; 15. o Division of Women's Health , King's College London , London , UK ; 16. 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 ; 17. q South Texas Diabetes and Obesity Institute, School of Medicine , University of Texas Rio Grande Valley , Brownsville , TX , USA ; 18. r School of Life Sciences , University of Nottingham , Nottingham , UK ; 19. s Faculty of Medicine Dentistry and Health Sciences , The University of Western Australia , Perth , Australia ; 20. t School of Biomedical Sciences , Faculty of Health Science, Curtin University , Perth , Australia ; 21. u Centre for Genetic Origins of Health and Disease, Medical Research Foundation , Royal Perth Hospital , Perth , Australia ; 22. v Institute for Molecular Medicine Finland , University of Helsinki , Helsinki , Finland.
Abstract
INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.