DINGO: increasing the power of locus discovery in maternal and fetal genome-wide association studies of perinatal traits.

Autor: Hwang LD; Institute for Molecular Bioscience, The University of Queensland, St Lucia, Australia. d.hwang@uq.edu.au., Cuellar-Partida G; Gilead Sciences, Inc, Foster City, CA, USA., Yengo L; Institute for Molecular Bioscience, The University of Queensland, St Lucia, Australia., Zeng J; Institute for Molecular Bioscience, The University of Queensland, St Lucia, Australia., Toivonen J; Finnish Red Cross Blood Service, Vantaa, Finland., Arvas M; Finnish Red Cross Blood Service, Vantaa, Finland., Beaumont RN; Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK., Freathy RM; Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK., Moen GH; Institute for Molecular Bioscience, The University of Queensland, St Lucia, Australia.; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.; Department of Public Health and Nursing, K.G. Jebsen Center for Genetic Epidemiology, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.; The Frazer Institute, The University of Queensland, Woolloongabba, QLD, Australia., Warrington NM; Institute for Molecular Bioscience, The University of Queensland, St Lucia, Australia.; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.; Department of Public Health and Nursing, K.G. Jebsen Center for Genetic Epidemiology, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.; The Frazer Institute, The University of Queensland, Woolloongabba, QLD, Australia., Evans DM; Institute for Molecular Bioscience, The University of Queensland, St Lucia, Australia. d.evans1@uq.edu.au.; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK. d.evans1@uq.edu.au.; The Frazer Institute, The University of Queensland, Woolloongabba, QLD, Australia. d.evans1@uq.edu.au.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Oct 26; Vol. 15 (1), pp. 9255. Date of Electronic Publication: 2024 Oct 26.
DOI: 10.1038/s41467-024-53495-9
Abstrakt: Perinatal traits are influenced by fetal and maternal genomes. We investigate the performance of three strategies to detect loci in maternal and fetal genome-wide association studies (GWASs) of the same quantitative trait: (i) the traditional strategy of analysing maternal and fetal GWASs separately; (ii) a two-degree-of-freedom test which combines information from maternal and fetal GWASs; and (iii) a one-degree-of-freedom test where signals from maternal and fetal GWASs are meta-analysed together conditional on estimated sample overlap. We demonstrate that the optimal strategy depends on the extent of sample overlap, correlation between phenotypes, whether loci exhibit fetal and/or maternal effects, and whether these effects are directionally concordant. We apply our methods to summary statistics from a recent GWAS meta-analysis of birth weight. Both the two-degree-of-freedom and meta-analytic approaches increase the number of genetic loci for birth weight relative to separately analysing the scans. Our best strategy identifies an additional 62 loci compared to the most recently published meta-analysis of birth weight. We conclude that whilst the two-degree-of-freedom test may be useful for the analysis of certain perinatal phenotypes, for most phenotypes, a simple meta-analytic strategy is likely to perform best, particularly in situations where maternal and fetal GWASs only partially overlap.
(© 2024. The Author(s).)
Databáze: MEDLINE
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