Browsing by Author "Laber, Samantha"

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    Large-scale meta-analysis highlights the hypothalamic–pituitary–gonadal axis in the genetic regulation of menstrual cycle length
    (Human Molecular Genetics, 2018) Laisk, Triin; Kukuškina, Viktorija; Palmer, Duncan; Laber, Samantha; Chen, Chia-Yen; Ferreira, Teresa; Rahmioglu, Nilufer; Zondervan, Krina; Becker, Christian; Smoller, Jordan W; Lippincott, Margaret; Salumets, Andres; Granne, Ingrid; Seminara, Stephanie; Neale, Benjamin; Mägi, Reedik; Lindgren, Cecilia M
    The normal menstrual cycle requires a delicate interplay between the hypothalamus, pituitary and ovary. Therefore, its length is an important indicator of female reproductive health. Menstrual cycle length has been shown to be partially controlled by genetic factors, especially in the follicle-stimulating hormone beta-subunit (FSHB) locus. A genome-wide association study meta-analysis of menstrual cycle length in 44 871 women of European ancestry confirmed the previously observed association with the FSHB locus and identified four additional novel signals in, or near, the GNRH1, PGR, NR5A2 and INS-IGF2 genes. These findings not only confirm the role of the hypothalamic–pituitary–gonadal axis in the genetic regulation of menstrual cycle length but also highlight potential novel local regulatory mechanisms, such as those mediated by IGF2.
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    The genetic architecture of sporadic and multiple consecutive miscarriage
    (Nature Communications, 2020-11-25) Laisk, Triin; Soares, Ana Luiza G.; Lindgren, Cecilia M.; Ferreira, Teresa; Painter, Jodie N.; Censin, Jenny C.; Laber, Samantha; Bacelis, Jonas; Chen, Chia-Yen; Lepamets, Maarja; Lawlor, Deborah A.; Mägi, Reedik; Medland, Sarah E.; Granne, Ingrid; Walters, Robin G.; Nielsen, Rasmus; Neale, Benjamin M.; Martin, Nicholas G.; Li, Liming; Jacobsson, Bo; Conrad, Donald F.; Chen, Zhengming; Werge, Thomas; Zondervan, Krina; Snieder, Harold; Salumets, Andres; Seminara, Stephanie; Lippincott, Margaret; Nyholt, Dale R.; Nordentoft, Merete; Njølstad, Pål R.; Mortensen, Preben B.; Mors, Ole; Morris, Andrew P.; Montgomery, Grant W.; Metspalu, Andres; Lind, Penelope A.; Kukushkina, Viktorija; Kartsonaki, Christiana; Juodakis, Julius; Johansson, Stefan; Jin, Xin; Hougaard, David M.; Helgeland, Øyvind; Bybjerg-Grauholm, Jonas; Gordon, Scott D.; Børglum, Anders D.; Becker, Christian M.; Yang, Ling; Andersen, Marianne S.; Southcombe, Jennifer; Ramu, Avinash; Millwood, Iona Y.; Liu, Siyang; Lin, Kuang
    Miscarriage is a common, complex trait affecting ~15% of clinically confirmed pregnancies. Here we present the results of large-scale genetic association analyses with 69,054 cases from five different ancestries for sporadic miscarriage, 750 cases of European ancestry for multiple (≥3) consecutive miscarriage, and up to 359,469 female controls. We identify one genome-wide significant association (rs146350366, minor allele frequency (MAF) 1.2%, P = 3.2 × 10−8, odds ratio (OR) = 1.4) for sporadic miscarriage in our European ancestry meta-analysis and three genome-wide significant associations for multiple consecutive miscarriage (rs7859844, MAF = 6.4%, P = 1.3 × 10−8, OR = 1.7; rs143445068, MAF = 0.8%, P = 5.2 × 10−9, OR = 3.4; rs183453668, MAF = 0.5%, P = 2.8 × 10−8, OR = 3.8). We further investigate the genetic architecture of miscarriage with biobank-scale Mendelian randomization, heritability, and genetic correlation analyses. Our results show that miscarriage etiopathogenesis is partly driven by genetic variation potentially related to placental biology, and illustrate the utility of large-scale biobank data for understanding this pregnancy complication.