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The joint meta-analysis (N\u2009=\u20094557) in two multiethnic cohorts of school-aged children identified one locus, <jats:italic>CYP11B1<\/jats:italic> (expression confined to the adrenal gland), robustly associated with SA (rs6471570-A; \u03b2\u2009=\u20090.14; <jats:italic>P<\/jats:italic>\u2009=\u20096.2 \u00d7 10<jats:sup>\u221212<\/jats:sup>). rs6410 (a synonymous variant in the first exon of <jats:italic>CYP11B1<\/jats:italic> in high LD with rs6471570), was prioritized for functional follow-up being second most significant and the one closest to the first intron-exon boundary. In 208 adrenal RNA-seq samples from GTEx, C-allele of rs6410 was associated with intron 3 retention (<jats:italic>P<\/jats:italic>\u2009=\u20098.11 \u00d7 10<jats:sup>\u221240<\/jats:sup>), exon 4 inclusion (<jats:italic>P<\/jats:italic>\u2009=\u20094.29 \u00d7 10<jats:sup>\u221234<\/jats:sup>), and decreased exon 3 and 5 splicing (<jats:italic>P<\/jats:italic>\u2009=\u20097.85 \u00d7 10<jats:sup>\u221243<\/jats:sup>), replicated using RT-PCR in 15 adrenal samples. As <jats:italic>CYP11B1<\/jats:italic> encodes 11-\u03b2-hydroxylase, involved in adrenal glucocorticoid and mineralocorticoid biosynthesis, our findings highlight the role of adrenal steroidogenesis in SA in healthy children, suggesting alternative splicing as a likely underlying mechanism.<\/jats:p>","DOI":"10.1038\/s42003-021-02774-y","type":"journal-article","created":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T11:03:01Z","timestamp":1636455781000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["CYP11B1 variants influence skeletal maturation via alternative splicing"],"prefix":"10.1038","volume":"4","author":[{"given":"Olja","family":"Grgic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew 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