Meta-analysis of genome-wide association studies of gestational duration and spontaneous preterm birth identifies new maternal risk loci.

Autor: Pasanen A; Research Unit of Clinical Medicine, Medical Research Center Oulu, University of Oulu, and Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland., Karjalainen MK; Research Unit of Population Health, Faculty of Medicine, University of Oulu, Oulu, Finland., Zhang G; Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Center for Prevention of Preterm Birth, Perinatal Institute and March of Dimes Prematurity Research Center Ohio Collaborative, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America., Tiensuu H; Research Unit of Clinical Medicine, Medical Research Center Oulu, University of Oulu, and Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland., Haapalainen AM; Research Unit of Clinical Medicine, Medical Research Center Oulu, University of Oulu, and Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland., Ojaniemi M; Research Unit of Clinical Medicine, Medical Research Center Oulu, University of Oulu, and Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland., Feenstra B; Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark., Jacobsson B; Department of Obstetrics and Gynaecology, Sahlgrenska Academy, Institute of Clinical Science, University of Gothenburg, Gothenburg, Sweden.; Department of Genetics and Bioinformatics, Health Data and Digitalization, Norwegian Institute of Public Health, Oslo, Norway., Palotie A; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America.; Psychiatric & Neurodevelopmental Genetics Unit, Department of Psychiatry, Analytic and Translational Genetics Unit, Department of Medicine, and the Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, United States of America., Laivuori H; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.; Center for Child, Adolescent, and Maternal Health Research, Faculty of Medicine and Health Technology, University of Tampere, Tampere, Finland.; Department of Obstetrics and Gynecology, Tampere University Hospital, Tampere, Finland., Muglia LJ; Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Center for Prevention of Preterm Birth, Perinatal Institute and March of Dimes Prematurity Research Center Ohio Collaborative, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America.; Burroughs Wellcome Fund, Research Triangle Park, Durham, North Carolina, United States of America., Rämet M; Research Unit of Clinical Medicine, Medical Research Center Oulu, University of Oulu, and Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland.; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland., Hallman M; Research Unit of Clinical Medicine, Medical Research Center Oulu, University of Oulu, and Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland.
Jazyk: angličtina
Zdroj: PLoS genetics [PLoS Genet] 2023 Oct 23; Vol. 19 (10), pp. e1010982. Date of Electronic Publication: 2023 Oct 23 (Print Publication: 2023).
DOI: 10.1371/journal.pgen.1010982
Abstrakt: Background: Preterm birth (<37 weeks of gestation) is a major cause of neonatal death and morbidity. Up to 40% of the variation in timing of birth results from genetic factors, mostly due to the maternal genome.
Methods: We conducted a genome-wide meta-analysis of gestational duration and spontaneous preterm birth in 68,732 and 98,370 European mothers, respectively.
Results: The meta-analysis detected 15 loci associated with gestational duration, and four loci associated with preterm birth. Seven of the associated loci were novel. The loci mapped to several biologically plausible genes, for example HAND2 whose expression was previously shown to decrease during gestation, associated with gestational duration, and GC (Vitamin D-binding protein), associated with preterm birth. Downstream in silico-analysis suggested regulatory roles as underlying mechanisms for the associated loci. LD score regression found birth weight measures as the most strongly correlated traits, highlighting the unique nature of spontaneous preterm birth phenotype. Tissue expression and colocalization analysis revealed reproductive tissues and immune cell types as the most relevant sites of action.
Conclusion: We report novel genetic risk loci that associate with preterm birth or gestational duration, and reproduce findings from previous genome-wide association studies. Altogether, our findings provide new insight into the genetic background of preterm birth. Better characterization of the causal genetic mechanisms will be important to public health as it could suggest new strategies to treat and prevent preterm birth.
Competing Interests: The authors declare no competing interests.
(Copyright: © 2023 Pasanen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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