{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T18:57:48Z","timestamp":1771268268039,"version":"3.50.1"},"reference-count":40,"publisher":"The Endocrine Society","issue":"1","license":[{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["K23 HD097296"],"award-info":[{"award-number":["K23 HD097296"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HD090071"],"award-info":[{"award-number":["R01 HD090071"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HD048960"],"award-info":[{"award-number":["R01 HD048960"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50 HD104224"],"award-info":[{"award-number":["P50 HD104224"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["M01 RR002172"],"award-info":[{"award-number":["M01 RR002172"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K23 RR15544"],"award-info":[{"award-number":["K23 RR15544"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["M01 RR000080"],"award-info":[{"award-number":["M01 RR000080"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HD008919"],"award-info":[{"award-number":["HD008919"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["ES103322"],"award-info":[{"award-number":["ES103322"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Environmental Health Science, Division of Intramural Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Constitutional delay of puberty (CDP) is highly heritable, but the genetic basis for CDP is largely unknown. Idiopathic hypogonadotropic hypogonadism (IHH) can be caused by rare genetic variants, but in about half of cases, no rare-variant cause is found.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To determine whether common genetic variants that influence pubertal timing contribute to CDP and IHH.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Case-control study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Participants<\/jats:title>\n                  <jats:p>80 individuals with CDP; 301 with normosmic IHH, and 348 with Kallmann syndrome (KS); control genotyping data from unrelated studies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main Outcome Measures<\/jats:title>\n                  <jats:p>Polygenic scores (PGS) based on genome-wide association studies for timing of male pubertal hallmarks and age at menarche (AAM).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The CDP cohort had higher PGS for male pubertal hallmarks and for AAM compared to controls (for male hallmarks, Cohen's d = 0.67, P = 1 \u00d7 10\u221210; for AAM, d = 0.85, P = 1 \u00d7 10\u221216). The normosmic IHH cohort also had higher PGS for male hallmarks compared to controls, but the difference was smaller (male hallmarks d = 0.20, P = .003; AAM d = 0.10, P = .055). No differences were seen for the KS cohort compared to controls (male hallmarks d = 0.05, P = .45; AAM d = 0.03, P = .56).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Common genetic variants that influence pubertal timing in the general population contribute strongly to the genetics of CDP, weakly to normosmic IHH, and potentially not at all to KS. These findings demonstrate that the common-variant genetics of CDP and normosmic IHH are largely but not entirely distinct.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgae166","type":"journal-article","created":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T14:43:32Z","timestamp":1710341012000},"page":"e61-e67","source":"Crossref","is-referenced-by-count":8,"title":["Contributions of Common Genetic Variants to Constitutional Delay of Puberty and Idiopathic Hypogonadotropic Hypogonadism"],"prefix":"10.1210","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3533-1999","authenticated-orcid":false,"given":"Margaret F","family":"Lippincott","sequence":"first","affiliation":[{"name":"Harvard Center for Reproductive Medicine, Department of Medicine, Massachusetts General Hospital , Boston, MA 02114 ,","place":["USA"]},{"name":"Departments of Medicine (M.F.L., S.B.S.), Pediatrics (J.N.H., Y.-M.C.), and Genetics (J.N.H.), Harvard Medical School , 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