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BMC Pregnancy and Childbirth
Published in: BMC Pregnancy and Childbirth 1/2024

Open Access 01-12-2024 | Hyperemesis Gravidarum | Research

Genome-wide association study of nausea and vomiting during pregnancy in Japan: the TMM BirThree Cohort Study

Authors: Yudai Yonezawa, Ippei Takahashi, Hisashi Ohseto, Fumihiko Ueno, Tomomi Onuma, Aoi Noda, Keiko Murakami, Mami Ishikuro, Taku Obara, Shinichi Kuriyama

Published in: BMC Pregnancy and Childbirth | Issue 1/2024

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Abstract

Background

Nausea and vomiting during pregnancy (NVP) and hyperemesis gravidarum (HG), common conditions affecting most pregnant women, are highly heritable and associated with maternal and fetal morbidity. However, the pathologies underlying NVP and HG and their associated loci are scarce.

Methods

We performed genome-wide association studies (GWAS) of NVP in pregnant women (n = 23,040) who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study in Japan from July 2013 to March 2017. Participants were divided into discovery (n = 9,464) and replication (n = 10,051) stages based on the platform used for their genotyping. Loci that achieved the genome-wide significance level (p < 5.0 × 10− 8) in the discovery stage were selected for genotyping in the replication stage. A meta-analysis integrating the discovery and replication stage results (n = 19,515) was conducted. NVP-related variables were identified as categorical or continuous.

Results

GWAS analysis in the discovery phase revealed loci linked to NVP in two gene regions, 11q22.1 (rs77775955) and 19p13.11 (rs749451 and rs28568614). Loci in these two gene regions have also been shown to be associated with HG in a White European population, indicating the generalizability of the GWAS analyses conducted in this study. Of these, only rs749451 and rs28568614 at 19p13.11 reached the genome-wide suggestive level (p < 1.0 × 10− 5) in the replication stage; however, both loci were significant in the meta-analysis.

Conclusions

NVP-related loci were identified in the Japanese population at 11q22.1 and 19p13.11, as reported in previous GWAS. This study contributes new evidence on the generalizability of previous GWAS on the association between genetic background and NVP.
Appendix
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Literature
1.
Gadsby R, Barnie-Adshead AM, Jagger C. A prospective study of nausea and vomiting during pregnancy. Br J Gen Pract. 1993;43:245–8.PubMedPubMedCentral
2.
Einarson TR, Piwko C, Koren G. Quantifying the global rates of nausea and vomiting of pregnancy: a meta analysis. J Popul Ther Clin Pharmacol. 2013;20:e171–83.PubMed
3.
London V, Grube S, Sherer DM, Abulafia O. Hyperemesis Gravidarum: a review of recent literature. Pharmacology. 2017;100:161–71.CrossRefPubMed
4.
Colodro-Conde L, Jern P, Johansson A, Sánchez-Romera JF, Lind PA, Painter JN, et al. Nausea and vomiting during pregnancy is highly heritable. Behav Genet. 2016;46:481–91.CrossRefPubMed
5.
Fejzo MS, Sazonova OV, Sathirapongsasuti JF, Hallgrímsdóttir IB, Vacic V, MacGibbon KW, et al. Placenta and appetite genes GDF15 and IGFBP7 are associated with hyperemesis gravidarum. Nat Commun. 2018;9:1178.ADSCrossRefPubMedPubMedCentral
6.
Changalidis AI, Maksiutenko EM, Barbitoff YA, Tkachenko AA, Vashukova ES, Pachuliia OV, et al. Aggregation of Genome-Wide Association Data from FinnGen and UK Biobank replicates multiple risk loci for pregnancy complications. Genes (Basel). 2022;13:2255.CrossRefPubMed
7.
Fejzo M, Zöllner J, Pujol-Gualdo N, Laisk T, Finer S, van Heel D, et al. GDF15, genetic risk factor for Hyperemesis Gravidarum, inversely Associated with pregnancy weight gain. Obstet Gynecol. 2023;141:73S–4.CrossRef
8.
Fejzo M, Rocha N, Cimino I, Lockhart SM, Petry C, Kay RG, et al. GDF15 linked to maternal risk of nausea and vomiting during pregnancy. Nature. 2024;625(7996):760–7.ADSCrossRefPubMed
9.
Kuriyama S, Metoki H, Kikuya M, Obara T, Ishikuro M, Yamanaka C, et al. Cohort Profile: Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study): rationale, progress and perspective. Int J Epidemiol. 2020;49:18–19m.CrossRefPubMed
10.
Kuriyama S, Yaegashi N, Nagami F, Arai T, Kawaguchi Y, Osumi N, et al. The Tohoku Medical Megabank Project: design and mission. J Epidemiol. 2016;26:493–511.CrossRefPubMed
11.
Sakurai-Yageta M, Kumada K, Gocho C, Makino S, Uruno A, Tadaka S, et al. Japonica array NEO with increased genome-wide coverage and abundant disease risk SNPs. J Biochem. 2021;170:399–410.CrossRefPubMedPubMedCentral
12.
Delaneau O, Zagury J-F, Marchini J. Improved whole-chromosome phasing for disease and population genetic studies. Nat Methods. 2013;10:5–6.CrossRefPubMed
13.
O’Connell J, Gurdasani D, Delaneau O, Pirastu N, Ulivi S, Cocca M, et al. A general approach for haplotype phasing across the full spectrum of relatedness. PLoS Genet. 2014;10:e1004234.CrossRefPubMedPubMedCentral
14.
Tadaka S, Katsuoka F, Ueki M, Kojima K, Makino S, Saito S, et al. 3.5KJPNv2: an allele frequency panel of 3552 Japanese individuals including the X chromosome. Hum Genome Var. 2019;6:28.CrossRefPubMedPubMedCentral
15.
1000 Genomes Project Consortium, Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, et al. A global reference for human genetic variation. Nature. 2015;526:68–74.CrossRef
16.
17.
Howie BN, Donnelly P, Marchini J. A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genet. 2009;5:e1000529.CrossRefPubMedPubMedCentral
18.
19.
Jiang L, Zheng Z, Fang H, Yang J. A generalized linear mixed model association tool for biobank-scale data. Nat Genet. 2021;53:1616–21.CrossRefPubMed
20.
Jiang L, Zheng Z, Qi T, Kemper KE, Wray NR, Visscher PM, et al. A resource-efficient tool for mixed model association analysis of large-scale data. Nat Genet. 2019;51:1749–55.CrossRefPubMed
21.
22.
Pruim RJ, Welch RP, Sanna S, Teslovich TM, Chines PS, Gliedt TP, et al. LocusZoom: regional visualization of genome-wide association scan results. Bioinformatics. 2010;26:2336–7.CrossRefPubMedPubMedCentral
23.
Ward LD, Kellis M. HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants. Nucleic Acids Res. 2012;40(Database issue):D930–4.CrossRefPubMed
24.
Mwanjewe J, Grover AK. Role of transient receptor potential canonical 6 (TRPC6) in non-transferrin-bound iron uptake in neuronal phenotype PC12 cells. Biochem J. 2004;378:975–82.CrossRefPubMedPubMedCentral
25.
26.
Gibon J, Tu P, Bohic S, Richaud P, Arnaud J, Zhu M, et al. The over-expression of TRPC6 channels in HEK-293 cells favours the intracellular accumulation of zinc. Biochim Biophys Acta. 2011;1808:2807–18.CrossRefPubMed
27.
Chevallet M, Jarvis L, Harel A, Luche S, Degot S, Chapuis V, et al. Functional consequences of the over-expression of TRPC6 channels in HEK cells: impact on the homeostasis of zinc. Metallomics. 2014;6:1269–76.CrossRefPubMed
28.
Hasna J, Abi Nahed R, Sergent F, Alfaidy N, Bouron A. The deletion of TRPC6 channels perturbs Iron and zinc homeostasis and pregnancy outcome in mice. Cell Physiol Biochem. 2019;52:455–67.CrossRefPubMed
29.
Tyrmi JS, Kaartokallio T, Lokki I, Jääskeläinen T, Kortelainen E, Ruotsalainen S et al. GWAS of preeclampsia and hypertensive disorders of pregnancy uncovers genes related to cardiometabolic, endothelial and placental function. Preprint medRxiv. 2022;2022.05.19.22275002.
30.
Fejzo MS, Trovik J, Grooten IJ, Sridharan K, Roseboom TJ, Vikanes Å, et al. Nausea and vomiting of pregnancy and hyperemesis gravidarum. Nat Rev Dis Primers. 2019;5:62.CrossRefPubMed
31.
Ho JE, Mahajan A, Chen M-H, Larson MG, McCabe EL, Ghorbani A, et al. Clinical and genetic correlates of growth differentiation factor 15 in the community. Clin Chem. 2012;58:1582–91.CrossRefPubMedPubMedCentral
32.
Moore AG, Brown DA, Fairlie WD, Bauskin AR, Brown PK, Munier ML, et al. The transforming growth factor-ss superfamily cytokine macrophage inhibitory cytokine-1 is present in high concentrations in the serum of pregnant women. J Clin Endocrinol Metab. 2000;85:4781–8.PubMed
33.
Tsai VW, Macia L, Johnen H, Kuffner T, Manadhar R, Jørgensen SB, et al. TGF-b superfamily cytokine MIC-1/GDF15 is a physiological appetite and body weight regulator. PLoS ONE. 2013;8:e55174.ADSCrossRefPubMedPubMedCentral
34.
Tsai VW, Manandhar R, Jørgensen SB, Lee-Ng KKM, Zhang HP, Marquis CP, et al. The anorectic actions of the TGFβ cytokine MIC-1/GDF15 require an intact brainstem area postrema and nucleus of the solitary tract. PLoS ONE. 2014;9:e100370.ADSCrossRefPubMedPubMedCentral
35.
Fejzo MS, MacGibbon KW, First O, Quan C, Mullin PM. Whole-exome sequencing uncovers new variants in GDF15 associated with hyperemesis gravidarum. BJOG. 2022;129(11):1845–52.CrossRefPubMedPubMedCentral
36.
Zhang Y, Peng S, Kuang H, Chen Q, Liu S, Zhang L, et al. Expression and regulation of Dickkopf2 during periimplantation in mice. J Reprod Dev. 2009;55:17–22.CrossRefPubMed
Metadata
Title
Genome-wide association study of nausea and vomiting during pregnancy in Japan: the TMM BirThree Cohort Study
Authors
Yudai Yonezawa
Ippei Takahashi
Hisashi Ohseto
Fumihiko Ueno
Tomomi Onuma
Aoi Noda
Keiko Murakami
Mami Ishikuro
Taku Obara
Shinichi Kuriyama
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Pregnancy and Childbirth / Issue 1/2024
Electronic ISSN: 1471-2393
DOI
https://doi.org/10.1186/s12884-024-06376-4

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