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We report analyses of rare variants that impact birth weight when carried by either fetus or mother, using whole exome sequencing data in up to 234,675 participants. Rare protein-truncating and deleterious missense variants are collapsed to perform gene burden tests. We identify 9 genes; 5 with fetal-only effects on birth weight, 1 with maternal-only effects, 3 with both, and observe directionally concordant associations in an independent sample. Four of the genes were previously implicated by GWAS of birth weight.\n                    <jats:italic>IGF1R<\/jats:italic>\n                    and\n                    <jats:italic>PAPPA2<\/jats:italic>\n                    (fetal and maternal-acting) have known roles in insulin-like growth factor bioavailability and signalling.\n                    <jats:italic>PPARG, INHBE<\/jats:italic>\n                    and\n                    <jats:italic>ACVR1C<\/jats:italic>\n                    (fetal-acting) are involved in adipose tissue regulation, and the latter two also show associations with favourable adiposity patterns in adults. We highlight the dual role of\n                    <jats:italic>PPARG<\/jats:italic>\n                    (fetal-acting) in adipocyte differentiation and placental angiogenesis.\n                    <jats:italic>NOS3<\/jats:italic>\n                    (fetal and maternal-acting)\n                    <jats:italic>, NRK<\/jats:italic>\n                    (fetal), and\n                    <jats:italic>ADAMTS8<\/jats:italic>\n                    (maternal-acting) have been implicated in placental function and hypertension. To conclude, our analysis of rare coding variants identifies regulators of fetal adipose tissue and fetoplacental angiogenesis as determinants of birth weight, and further evidence for the role of insulin-like growth factors.\n                  <\/jats:p>","DOI":"10.1038\/s41467-024-55761-2","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T07:48:37Z","timestamp":1736840917000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Rare variant associations with birth weight identify genes involved in adipose tissue regulation, placental function and insulin-like growth factor signalling"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5816-664X","authenticated-orcid":false,"given":"Katherine A.","family":"Kentistou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon E. 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