The genetic architecture of sporadic and recurrent miscarriage
Triin Laisk,Ana Luiza Gonçalves Soares,Teresa Ferreira,Jodie N. Painter,Samantha Laber,Jonas Bacelis,Chia-Yen Chen,Chia-Yen Chen,Maarja Lepamets,Kuang Lin,Siyang Liu,Iona Y Millwood,Iona Y Millwood,Avinash Ramu,J Southcombe,Marianne Andersen,Ling Yang,Ling Yang,Christian M. Becker,Scott D. Gordon,Jonas Bybjerg-Grauholm,Jonas Bybjerg-Grauholm,Øyvind Helgeland,Øyvind Helgeland,David M. Hougaard,David M. Hougaard,Xin Jin,Stefan Johansson,Stefan Johansson,Julius Juodakis,Christiana Kartsonaki,Christiana Kartsonaki,Viktorija Kukushkina,Penelope A. Lind,Andres Metspalu,Grant W. Montgomery,Andrew P. Morris,Andrew P. Morris,Andrew P. Morris,Preben Bo Mortensen,Preben Bo Mortensen,Pål R. Njølstad,Pål R. Njølstad,Dale R. Nyholt,Margaret F. Lippincott,Stephanie B. Seminara,Andres Salumets,Harold Snieder,Krina T. Zondervan,Zhengming Chen,Donald F. Conrad,Bo Jacobsson,Bo Jacobsson,Liming Li,Nicholas G. Martin,Benjamin M. Neale,Benjamin M. Neale,Rasmus Nielsen,Rasmus Nielsen,Robin G. Walters,Robin G. Walters,Ingrid Granne,Sarah E. Medland,Reedik Mägi,Debbie A Lawlor,Cecilia M. Lindgren,Cecilia M. Lindgren +66 more
TLDR
The results implicate that miscarriage etiopathogenesis is partly driven by genetic variation related to gonadotropin regulation, placental biology and progesterone production, as well as biobank-scale Mendelian randomization, heritability and, genetic correlation analyses.Abstract:
Miscarriage is a common complex trait that affects 10-25% of clinically confirmed pregnancies1,2. Here we present the first large-scale genetic association analyses with 69,118 cases from five different ancestries for sporadic miscarriage and 750 cases of European ancestry for recurrent miscarriage, and up to 359,469 female controls. We identify one genome-wide significant association on chromosome 13 (rs146350366, minor allele frequency (MAF) 1.2%, Pmeta=3.2× -8 (CI) 1.2-1.6) for sporadic miscarriage in our European ancestry meta-analysis (50,060 cases and 174,109 controls), located near FGF9 involved in pregnancy maintenance3 and progesterone production4. Additionally, we identified three genome-wide significant associations for recurrent miscarriage, including a signal on chromosome 9 (rs7859844, MAF=6.4%, Pmeta=1.3× -8 in controlling extravillous trophoblast motility5. We further investigate the genetic architecture of miscarriage with biobank-scale Mendelian randomization, heritability and, genetic correlation analyses. Our results implicate that miscarriage etiopathogenesis is partly driven by genetic variation related to gonadotropin regulation, placental biology and progesterone production.read more
Citations
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Journal ArticleDOI
Recurrent pregnancy loss.
TL;DR: Recurrent pregnancy loss is a distressing pregnancy disorder experienced by approximately 25% of women trying to conceive as mentioned in this paper, it is defined as the failure of two or more clinically recognized pregnancies before 20-24 weeks of gestation and includes embryonic and fetal losses.
Journal ArticleDOI
Genomic Analysis of Spontaneous Abortion in Holstein Heifers and Primiparous Cows.
Kayleen F Oliver,Alexandria M Wahl,Mataya Dick,Jewel A Toenges,J. N. Kiser,Justine M Galliou,J.G.N. Moraes,Gregory W. Burns,J.C. Dalton,Thomas E. Spencer,Holly L. Neibergs +10 more
TL;DR: A genome-wide association analysis, gene-set enrichment analysis–single nucleotide polymorphism, and ingenuity pathway analysis were used to identify regions, pathways, and master regulators associated with SA in heifers, cows, and a combined population.
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