Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth.
Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth.
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DOI：
10.1038/s41588-023-01520-w
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发表时间：
2023-11
期刊：
影响因子：
30.8
通讯作者：
Njolstad, Pal R.
中科院分区：
文献类型：
--
作者：
Beaumont, Robin N.;Flatley, Christopher;Vaudel, Marc;Wu, Xiaoping;Chen, Jing;Moen, Gunn-Helen;Skotte, Line;Helgeland, Oyvind;Sole-Navais, Pol;Banasik, Karina;Albinana, Clara;Ronkainen, Justiina;Fadista, Joao;Stinson, Sara Elizabeth;Trajanoska, Katerina;Wang, Carol A.;Westergaard, David;Srinivasan, Sundararajan;Sanchez-Soriano, Carlos;Bilbao, Jose Ramon;Allard, Catherine;Groleau, Marika;Kuulasmaa, Teemu;Leirer, Daniel J.;White, Frederique;Jacques, Pierre-Etienne;Cheng, Haoxiang;Hao, Ke;Andreassen, Ole A.;Asvold, Bjorn Olav;Atalay, Mustafa;Bhatta, Laxmi;Bouchard, Luigi;Brumpton, Ben Michael;Brunak, Soren;Bybjerg-Grauholm, Jonas;Ebbing, Cathrine;Elliott, Paul;Engelbrechtsen, Line;Erikstrup, Christian;Estarlich, Marisa;Franks, Stephen;Gaillard, Romy;Geller, Frank;Grove, Jakob;Hougaard, David M.;Kajantie, Eero;Morgen, Camilla S.;Nohr, Ellen A.;Nyegaard, Mette;Palmer, Colin N. A.;Pedersen, Ole Birger;Rivadeneira, Fernando;Sebert, Sylvain;Shields, Beverley M.;Stoltenberg, Camilla;Surakka, Ida;Thorner, Lise Wegner;Ullum, Henrik;Vaarasmaki, Marja;Vilhjalmsson, Bjarni J.;Willer, Cristen J.;Lakka, Timo A.;Gybel-Brask, Dorte;Bustamante, Mariona;Hansen, Torben;Pearson, Ewan R.;Reynolds, Rebecca M.;Ostrowski, Sisse R.;Pennell, Craig E.;Jaddoe, Vincent W. V.;Felix, Janine F.;Hattersley, Andrew T.;Melbye, Mads;Lawlor, Deborah A.;Hveem, Kristian;Werge, Thomas;Nielsen, Henriette Svarre;Magnus, Per;Evans, David M.;Jacobsson, Bo;Jarvelin, Marjo-Riitta;Zhang, Ge;Hivert, Marie-France;Johansson, Stefan;Freathy, Rachel M.;Feenstra, Bjarke;Njolstad, Pal R.;Beaumont, Robin N.;Flatley, Christopher;Vaudel, Marc;Wu, Xiaoping;Moen, Gunn-Helen;Skotte, Line;Helgeland, Oyvind;Sole-Navais, Pol;Ronkainen, Justiina;Fadista, Joao;Stinson, Sara Elizabeth;Wang, Carol A.;Bilbao, Jose Ramon;Atalay, Mustafa;Elliott, Paul;Gaillard, Romy;Geller, Frank;Morgen, Camilla S.;Nohr, Ellen A.;Sebert, Sylvain;Lakka, Timo A.;Bustamante, Mariona;Hansen, Torben;Reynolds, Rebecca M.;Pennell, Craig E.;Jaddoe, Vincent W. V.;Felix, Janine F.;Hattersley, Andrew T.;Melbye, Mads;Lawlor, Deborah A.;Magnus, Per;Evans, David M.;Jacobsson, Bo;Jarvelin, Marjo-Riitta;Zhang, Ge;Hivert, Marie-France;Johansson, Stefan;Freathy, Rachel M.;Feenstra, Bjarke;Njolstad, Pal R.
一个功能良好的胎盘在整个怀孕期间对胎儿和母亲的健康至关重要。使用胎盘重量作为胎盘生长的代表，我们报告了胎儿（n = 65，405），母体（n = 61，228）和父亲（n = 52，392）基因组的全基因组关联分析，产生了40个独立的关联信号。26个信号被分类为胎儿、4个母体和3个胎儿和母体。在KCNQ1附近观察到母体的起源亲本效应。遗传相关性和共定位分析显示与出生体重遗传学重叠，但12个位点被归类为主要或仅影响胎盘重量，与胎盘发育和形态学以及抗体和氨基酸的运输有关。孟德尔随机化分析表明，胎儿遗传介导的胎盘重量较高与先兆子痫风险和妊娠期缩短有因果关系。此外，这些分析支持胎儿胰岛素在调节胎盘重量中的作用，提供了胎儿和胎盘生长之间的关键联系。使用胎儿和父母基因型的全基因组分析确定了40个影响胎盘重量的独立关联，并强调了胎儿在先兆子痫风险和通过胰岛素信号传导调节胎盘生长中的作用。
A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n = 65,405), maternal (n = 61,228) and paternal (n = 52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth. Genome-wide analyses using fetal and parental genotypes identify 40 independent associations influencing placental weight and highlight the role of the fetus in preeclampsia risk and placental growth regulation via insulin signaling.
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影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
9.2
作者：
Bourgey, Mathieu;Dali, Rola;Bourque, Guillaume
通讯作者：
Bourque, Guillaume
影响因子：
64.8
作者：
Coorens THH;Oliver TRW;Sanghvi R;Sovio U;Cook E;Vento-Tormo R;Haniffa M;Young MD;Rahbari R;Sebire N;Campbell PJ;Charnock-Jones DS;Smith GCS;Behjati S
通讯作者：
Behjati S
影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.