Maternal plasma cortisol's effect on offspring birth weight: a Mendelian Randomisation study.
Maternal plasma cortisol's effect on offspring birth weight: a Mendelian Randomisation study.
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DOI：
10.1186/s12884-024-06250-3
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发表时间：
2024-01-15
影响因子：
3.1
通讯作者：
中科院分区：
文献类型：
--
作者：
观察性研究和随机对照试验发现，有证据表明，怀孕期间母亲循环皮质醇水平较高与后代出生体重较低有关。然而，观察到的关联可能是由于残留的混淆。我们使用与清晨血浆皮质醇相关的单一基因变异(Rs9989237)进行了两样本孟德尔随机化(MR)。根据发表的鸡蛋协会和英国生物库荟萃分析(GWAS；样本2；N=高达406,063)，根据胎儿基因调整后的母体基因变异与后代出生体重之间的关联，并使用Wald比率来估计因果影响。我们还进行了一项替代分析，使用了所有GWAS报告的皮质醇变种，考虑了连锁不平衡。我们还测试了基因变异对妊娠皮质醇的影响，并进行了PheWas以寻找潜在的多效性效应。使用单一变量，母体循环皮质醇对出生体重的影响估计为50克(95%可信区间，-109至10)，每1 SD新生儿体重降低对数转换的母体循环皮质醇水平较高。另一种分析给出了类似的结果(-33克(95%可信区间，-77到11))。皮质醇变异对妊娠皮质醇的影响比最初的GWA弱2倍，并发现了多效性的证据。我们的发现提供了一些证据，表明较高的产妇早晨血浆皮质醇会导致较低的出生体重。有必要确定更多独立的清晨血浆皮质醇基因仪器，以探索已确定的潜在偏差。网上版载有补充材料，可在10.1186/s12884-024-06250-3查阅。
Observational studies and randomized controlled trials have found evidence that higher maternal circulating cortisol levels in pregnancy are associated with lower offspring birth weight. However, it is possible that the observational associations are due to residual confounding. We performed two-sample Mendelian Randomisation (MR) using a single genetic variant (rs9989237) associated with morning plasma cortisol (GWAS; sample 1; N = 25,314). The association between this maternal genetic variant and offspring birth weight, adjusted for fetal genotype, was obtained from the published EGG Consortium and UK Biobank meta-analysis (GWAS; sample 2; N = up to 406,063) and a Wald ratio was used to estimate the causal effect. We also performed an alternative analysis using all GWAS reported cortisol variants that takes account of linkage disequilibrium. We also tested the genetic variant’s effect on pregnancy cortisol and performed PheWas to search for potential pleiotropic effects. The estimated effect of maternal circulating cortisol on birth weight was a 50 gram (95% CI, -109 to 10) lower birth weight per 1 SD higher log-transformed maternal circulating cortisol levels, using a single variant. The alternative analysis gave similar results (-33 grams (95% CI, -77 to 11)). The effect of the cortisol variant on pregnancy cortisol was 2-fold weaker than in the original GWAS, and evidence was found of pleiotropy. Our findings provide some evidence that higher maternal morning plasma cortisol causes lower birth weight. Identification of more independent genetic instruments for morning plasma cortisol are necessary to explore the potential bias identified. The online version contains supplementary material available at 10.1186/s12884-024-06250-3.
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影响因子：
64.8
作者：
Horikoshi, Momoko;Beaumont, Robin N.;Day, Felix R.;Warrington, Nicole M.;Kooijman, Marjolein N.;Fernandez-Tajes, Juan;Feenstra, Bjarke;van Zuydam, Natalie R.;Gaulton, Kyle J.;Grarup, Niels;Bradfield, Jonathan P.;Strachan, David P.;Li-Gao, Ruifang;Ahluwalia, Tarunveer S.;Kreiner, Eskil;Rueedi, Rico;Lyytikainen, Leo-Pekka;Cousminer, Diana L.;Wu, Ying;Thiering, Elisabeth;Wang, Carol A.;Have, Christian T.;Hottenga, Jouke-Jan;Vilor-Tejedor, Natalia;Joshi, Peter K.;Boh, Eileen Tai Hui;Ntalla, Ioanna;Pitkanen, Niina;Mahajan, Anubha;van Leeuwen, Elisabeth M.;Joro, Raimo;Lagou, Vasiliki;Nodzenski, Michael;Diver, Louise A.;Zondervan, Krina T.;Bustamante, Mariona;Marques-Vidal, Pedro;Mercader, Josep M.;Bennett, Amanda J.;Rahmioglu, Nilufer;Nyholt, Dale R.;Ma, Ronald C. W.;Tam, Claudia H. T.;Tam, Wing Hung;Ganesh, Santhi K.;van Rooij, Frank J. A.;Jones, Samuel E.;Loh, Po-Ru;Ruth, Katherine S.;Tuke, Marcus A.;Tyrrell, Jessica;Wood, Andrew R.;Yaghootkar, Hanieh;Scholtens, Denise M.;Paternoster, Lavinia;Prokopenko, Inga;Kovacs, Peter;Atalay, Mustafa;Willems, Sara M.;Panoutsopoulou, Kalliope;Wang, Xu;Carstensen, Lisbeth;Geller, Frank;Schraut, Katharina E.;Murcia, Mario;van Beijsterveldt, Catharina E. M.;Willemsen, Gonneke;Appel, Emil V. R.;Fonvig, Cilius E.;Trier, Caecilie;Tiesler, Carla M. T.;Standl, Marie;Kutalik, Zoltan;Bonas-Guarch, Silvia;Hougaard, David M.;Sanchez, Friman;Torrents, David;Waage, Johannes;Hollegaard, Mads V.;de Haan, Hugoline G.;Rosendaal, Frits R.;Medina-Gomez, Carolina;Ring, Susan M.;Hemani, Gibran;McMahon, George;Robertson, Neil R.;Groves, Christopher J.;Langenberg, Claudia;Luan, Jian'an;Scott, Robert A.;Zhao, Jing Hua;Mentch, Frank D.;MacKenzie, Scott M.;Reynolds, Rebecca M.;Lowe, William L.;Toenjes, Anke;Stumvoll, Michael;Lindi, Virpi;Lakka, Timo A.;van Duijn, Cornelia M.;Kiess, Wieland;Koerner, Antje;Sorensen, Thorkild I. A.;Niinikoski, Harri;Pahkala, Katja;Raitakari, Olli T.;Zeggini, Eleftheria;Dedoussis, George V.;Teo, Yik-Ying;Saw, Seang-Mei;Melbye, Mads;Campbell, Harry;Wilson, James F.;Vrijheid, Martine;de Geus, Eco J. C. N.;Boomsma, Dorret I.;Kadarmideen, Haja N.;Holm, Jens-Christian;Hansen, Torben;Sebert, Sylvain;Hattersley, Andrew T.;Beilin, Lawrence J.;Newnham, John P.;Pennell, Craig E.;Heinrich, Joachim;Adair, Linda S.;Borja, Judith B.;Mohlke, Karen L.;Eriksson, Johan G.;Widen, Elisabeth;Kahonen, Mika;Viikari, Jorma S.;Lehtimaki, Terho;Vollenweider, Peter;Bonnelykke, Klaus;Bisgaard, Hans;Mook-Kanamori, Dennis O.;Hofman, Albert;Rivadeneira, Fernando;Uitterlinden, Andre G.;Pisinger, Charlotta;Pedersen, Oluf;Power, Christine;Hyppoenen, Elina;Wareham, Nicholas J.;Hakonarson, Hakon;Davies, Eleanor;Walker, Brian R.;Jaddoe, Vincent W. V.;Jaervelin, Marjo-Riitta;Grant, Struan F. A.;Vaag, Allan A.;Lawlor, Debbie A.;Frayling, Timothy M.;Smith, George Davey;Morris, Andrew P.;Ong, Ken K.;Felix, Janine F.;Timpson, Nicholas J.;Perry, John R. B.;Evans, David M.;McCarthy, Mark I.;Freathy, Rachel M.
通讯作者：
Freathy, Rachel M.
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：
3.5
作者：
Crawford AA;Bankier S;Altmaier E;Barnes CLK;Clark DW;Ermel R;Friedrich N;van der Harst P;Joshi PK;Karhunen V;Lahti J;Mahajan A;Mangino M;Nethander M;Neumann A;Pietzner M;Sukhavasi K;Wang CA;Bakker SJL;Bjorkegren JLM;Campbell H;Eriksson J;Gieger C;Hayward C;Jarvelin MR;McLachlan S;Morris AP;Ohlsson C;Pennell CE;Price J;Rudan I;Ruusalepp A;Spector T;Tiemeier H;Völzke H;Wilson JF;Michoel T;Timpson NJ;Smith GD;Walker BR;CORtisol NETwork (CORNET) consortium
通讯作者：
CORtisol NETwork (CORNET) consortium
影响因子：
3.7
作者：
Goedhart, Geertje;Vrijkotte, Tanja G. M.;Bonsel, Gouke J.
通讯作者：
Bonsel, Gouke J.
影响因子：
2.8
作者：
Knight, B;Shields, BM;Hattersley, AT
通讯作者：
Hattersley, AT