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

Author

Steinthorsdottir, Valgerdur, McGinnis, Ralph, Williams, Nicholas O., Stefansdottir, Lilja, Thorleifsson, Gudmar, Shooter, Scott, Sigurdsson, Jon K., Auro, Kirsi M., Berezina, Galina, Borges, MariaCarolina, Bumpstead, Suzannah, Bybjerg-Grauholm, Jonas, Colgiu, Irina, Dolby, Vivien A., Dudbridge, Frank, Engel, Stephanie M., Franklin, Christopher S., Frigge, Michael L., Frisbaek, Yr, Geirsson, Reynir T., Geller, Frank, Gretarsdottir, Solveig, Gudbjartsson, Daniel F., Harmon, Quaker, Hougaard, David Michael, Hegay, Tatyana, Helgadottir, Anna, Hjartardottir, Sigrun, Johannsdottir, Hrefna, Jonsdottir, Ingileif, Juliusdottir, Thorhildur, Kalsheker, Noor, Kasimov, Abdumadjit, Kemp, John P., Kivinen, Katja, Lee, Wai K., Melbye, Mads, Miedzybrodska, Zosia, Moffett, Ashley, Najmutdinova, Dilbar, Nishanova, Firuza, Olafsdottir, Thorunn, Perola, Markus, Broughton Pipkin, Fiona, Poston, Lucilla, Prescott, Gordon, Saevarsdottir, Saedis, Salimbayeva, Damilya, Juliet Scaife, Paula, Skotte, Line, Staines-Urias, Eleonora, Stefansson, Olafur A., Cecilie Vestrheim Thomsen, Liv, Tragante, Vinicius, Trogstad, Lill, Simpson, Nigel A.B., FINNPEC Consortium, GOPEC Consortium, Aripova, Tamara, Casas, Juan P., Dominiczak, Anna F., Walker, James J., Thorsteinsdottir, Unnur, Iversen, Ann-Charlotte, Feenstra, Bjarke, Lawlor, Deborah A., Boyd, Heather Allison, Magnus, Per, Laivuori, Hannele, Zakhidova, Nodira, Svyatova, Gulnara, Stefansson, Kari, and Morgan, Linda

Subjects
General Physics and Astronomy, General Chemistry, General Biochemistry, Genetics and Molecular Biology
Published
2020

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

Author

Steinthorsdottir, Valgerdur, McGinnis, Ralph, Williams, Nicholas O., Stefansdottir, Lilja, Thorleifsson, Gudmar, Shooter, Scott, Fadista, João, Sigurdsson, Jon K., Auro, Kirsi M., Berezina, Galina, Borges, Maria-Carolina, Bumpstead, Suzannah, Bybjerg-Grauholm, Jonas, Colgiu, Irina, Dolby, Vivien A., Dudbridge, Frank, Engel, Stephanie M., Franklin, Christopher S., Frigge, Michael L., Frisbaek, Yr, Geirsson, Reynir T., Geller, Frank, Gretarsdottir, Solveig, Gudbjartsson, Daniel F., Harmon, Quaker, Hougaard, David Michael, Hegay, Tatyana, Helgadottir, Anna, Hjartardottir, Sigrun, Jääskeläinen, Tiina, Johannsdottir, Hrefna, Jonsdottir, Ingileif, Juliusdottir, Thorhildur, Kalsheker, Noor, Kasimov, Abdumadjit, Kemp, John P., Klungsøyr, Kari, Lee, Wai K., Melbye, Mads, Miedzybrodska, Zosia, Moffett, Ashley, Najmutdinova, Dilbar, Nishanova, Firuza, Olafsdottir, Thorunn, Perola, Markus, Poston, Lucilla, Prescott, Gordon, Saevarsdottir, Saedis, Salimbayeva, Damilya, Scaife, Paula Juliet, Skotte, Line, Staines-Urias, Eleonora, Stefansson, Olafur A., Sørensen, Karina Meden, Thomsen, Liv Cecilie Vestrheim, Tragante, Vinicius, Trogstad, Lill, Simpson, Nigel A. B., Aripova, Tamara, Casas, Juan P., Thorsteinsdottir, Unnur, Iversen, Ann-Charlotte, Feenstra, Bjarke, Lawlor, Deborah A., Boyd, Heather Allison, Magnus, Per, Zakhidova, Nodira, Svyatova, Gulnara, Stefansson, Kari, Laivuori, Hannele, Heinonen, Seppo, Kajantie, Eero, Kere, Juha, Kivinen, Katja, Pouta, Anneli, Morgan, Linda, Pipkin, Fiona Broughton, Walker, James J., Macphail, Sheila, Kilby, Mark, Habiba, Marwan, Williamson, Catherine, O’Shaughnessy, Kevin, O’Brien, Shaughn, Cameron, Alan, Redman, Christopher W. G., Farrall, Martin, Caulfield, Mark, and Dominiczak, Anna F.

Subjects
2. Zero hunger, 45, 692/699/75/243, 631/208/205/2138, 45/43, article, 692/699/2732, 3. Good health
Abstract

Funder: EC | EC Seventh Framework Programm | FP7 Health (FP7-HEALTH - Specific Programme "Cooperation": Health); doi: https://doi.org/10.13039/100011272; Grant(s): 282540, 282540, 282540, 282540, 282540, 282540, 282540, 282540, 282540, 282540, 282540, 282540, 282540, 282540, 282540, 282540, 282540, 282540, 282540, 282540, 282540, 282540, 282540, 282540, 282540, 282540, 282540, Funder: EC | EC Seventh Framework Programm | FP7 Health (FP7-HEALTH - Specific Programme "Cooperation": Health), Funder: U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), 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/3q26, FGF5/4q21 and SH2B3/12q24 also associate with preeclampsia through the maternal genome. We further show that a polygenic risk score for hypertension associates with preeclampsia. However, comparison with gestational hypertension indicates that additional factors modify the risk of preeclampsia.

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

Author

Steinthorsdottir, Valgerdur, McGinnis, Ralph, Williams, Nicholas O, Stefansdottir, Lilja, Thorleifsson, Gudmar, Shooter, Scott, Fadista, João, Sigurdsson, Jon K, Auro, Kirsi M, Berezina, Galina, Borges, Maria-Carolina, Bumpstead, Suzannah, Bybjerg-Grauholm, Jonas, Colgiu, Irina, Dolby, Vivien A, Dudbridge, Frank, Engel, Stephanie M, Franklin, Christopher S, Frigge, Michael L, Frisbaek, Yr, Geirsson, Reynir T, Geller, Frank, Gretarsdottir, Solveig, Gudbjartsson, Daniel F, Harmon, Quaker, Hougaard, David Michael, Hegay, Tatyana, Helgadottir, Anna, Hjartardottir, Sigrun, Jääskeläinen, Tiina, Johannsdottir, Hrefna, Jonsdottir, Ingileif, Juliusdottir, Thorhildur, Kalsheker, Noor, Kasimov, Abdumadjit, Kemp, John P, Kivinen, Katja, Klungsøyr, Kari, Lee, Wai K, Melbye, Mads, Miedzybrodska, Zosia, Moffett, Ashley, Najmutdinova, Dilbar, Nishanova, Firuza, Olafsdottir, Thorunn, Perola, Markus, Pipkin, Fiona Broughton, Poston, Lucilla, Prescott, Gordon, Saevarsdottir, Saedis, Salimbayeva, Damilya, Scaife, Paula Juliet, Skotte, Line, Staines-Urias, Eleonora, Stefansson, Olafur A, Sørensen, Karina Meden, Thomsen, Liv Cecilie Vestrheim, Tragante, Vinicius, Trogstad, Lill, Simpson, Nigel AB, FINNPEC Consortium, GOPEC Consortium, Aripova, Tamara, Casas, Juan P, Dominiczak, Anna F, Walker, James J, Thorsteinsdottir, Unnur, Iversen, Ann-Charlotte, Feenstra, Bjarke, Lawlor, Deborah A, Boyd, Heather Allison, Magnus, Per, Laivuori, Hannele, Zakhidova, Nodira, Svyatova, Gulnara, Stefansson, Kari, and Morgan, Linda

Subjects
Adult, Multifactorial Inheritance, Fibroblast Growth Factor 5, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Datasets as Topic, Blood Pressure, Pre-Eclampsia, Pregnancy, Humans, Genetic Predisposition to Disease, Prospective Studies, reproductive and urinary physiology, Adaptor Proteins, Signal Transducing, Aged, 2. Zero hunger, Hypertension, Pregnancy-Induced, Middle Aged, female genital diseases and pregnancy complications, MDS1 and EVI1 Complex Locus Protein, 3. Good health, Europe, Genetic Loci, Case-Control Studies, embryonic structures, Asia, Central, Female, Genome-Wide Association Study
Abstract

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/3q26, FGF5/4q21 and SH2B3/12q24 also associate with preeclampsia through the maternal genome. We further show that a polygenic risk score for hypertension associates with preeclampsia. However, comparison with gestational hypertension indicates that additional factors modify the risk of preeclampsia.

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

Author

Steinthorsdottir V, McGinnis R, Williams NO, Stefansdottir L, Thorleifsson G, Shooter S, Fadista J, Sigurdsson JK, Auro KM, Berezina G, Borges MC, Bumpstead S, Bybjerg-Grauholm J, Colgiu I, Dolby VA, Dudbridge F, Engel SM, Franklin CS, Frigge ML, Frisbaek Y, Geirsson RT, Geller F, Gretarsdottir S, Gudbjartsson DF, Harmon Q, Hougaard DM, Hegay T, Helgadottir A, Hjartardottir S, Jääskeläinen T, Johannsdottir H, Jonsdottir I, Juliusdottir T, Kalsheker N, Kasimov A, Kemp JP, Kivinen K, Klungsøyr K, Lee WK, Melbye M, Miedzybrodska Z, Moffett A, Najmutdinova D, Nishanova F, Olafsdottir T, Perola M, Pipkin FB, Poston L, Prescott G, Saevarsdottir S, Salimbayeva D, Scaife PJ, Skotte L, Staines-Urias E, Stefansson OA, Sørensen KM, Thomsen LCV, Tragante V, Trogstad L, Simpson NAB, Aripova T, Casas JP, Dominiczak AF, Walker JJ, Thorsteinsdottir U, Iversen AC, Feenstra B, Lawlor DA, Boyd HA, Magnus P, Laivuori H, Zakhidova N, Svyatova G, Stefansson K, and Morgan L

Subjects
Adaptor Proteins, Signal Transducing genetics, Adult, Aged, Alpha-Ketoglutarate-Dependent Dioxygenase FTO genetics, Asia, Central epidemiology, Blood Pressure genetics, Case-Control Studies, Datasets as Topic, Europe epidemiology, Female, Fibroblast Growth Factor 5 genetics, Genetic Loci genetics, Genome-Wide Association Study, Humans, Hypertension, Pregnancy-Induced epidemiology, MDS1 and EVI1 Complex Locus Protein genetics, Middle Aged, Pre-Eclampsia epidemiology, Pregnancy, Prospective Studies, Genetic Predisposition to Disease, Hypertension, Pregnancy-Induced genetics, Multifactorial Inheritance, Pre-Eclampsia genetics
Abstract

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/3q26, FGF5/4q21 and SH2B3/12q24 also associate with preeclampsia through the maternal genome. We further show that a polygenic risk score for hypertension associates with preeclampsia. However, comparison with gestational hypertension indicates that additional factors modify the risk of preeclampsia.

Published
2020
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