{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T22:16:24Z","timestamp":1785795384718,"version":"3.56.0"},"reference-count":68,"publisher":"The Royal Society","issue":"2033","license":[{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/-\/media\/journals\/author\/Licence-to-Publish-20062019-final.pdf"},{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"US National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["Proc. R. Soc. B."],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:p>The human sex ratio (fraction of males) at birth is close to 0.5 at the population level, an observation commonly explained by Fisher\u2019s principle. However, past human studies yielded conflicting results regarding the existence of sex ratio-influencing mutations\u2014a prerequisite to Fisher\u2019s principle, raising the question of whether the nearly even population sex ratio is instead dictated by the random X\/Y chromosome segregation in male meiosis. Here we show that, because a person\u2019s offspring sex ratio (OSR) has an enormous measurement error, a gigantic sample is required to detect OSR-influencing genetic variants. Conducting a UK Biobank-based genome-wide association study that is more powerful than previous studies, we detect an OSR-associated genetic variant, which awaits verification in independent samples. Given the abysmal precision in measuring OSR, it is unsurprising that the estimated heritability of OSR is effectively zero. We further show that OSR\u2019s estimated heritability would remain virtually zero even if OSR is as genetically variable as the highly heritable human standing height. These analyses, along with simulations of human sex ratio evolution under selection, demonstrate the compatibility of the observed genetic architecture of human OSR with Fisher\u2019s principle and render it plausible that multiple OSR-influencing genetic variants segregate among humans.<\/jats:p>","DOI":"10.1098\/rspb.2024.1876","type":"journal-article","created":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T23:06:46Z","timestamp":1729033606000},"update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["In search of the genetic variants of human sex ratio at birth: was Fisher wrong about sex ratio evolution?"],"prefix":"10.1098","volume":"291","author":[{"given":"Siliang","family":"Song","sequence":"first","affiliation":[{"name":"Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6141-1290","authenticated-orcid":true,"given":"Jianzhi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2024,10,16]]},"reference":[{"key":"e_1_3_8_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/415033"},{"key":"e_1_3_8_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/evo.12001"},{"key":"e_1_3_8_4_2","volume-title":"The descent of man, and selection in relation to sex","author":"Darwin C","year":"1871","unstructured":"Darwin C. 1871 The descent of man, and selection in relation to sex. London, UK: John Murray. (doi:10.5962\/bhl.title.24784)"},{"key":"e_1_3_8_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-185X.1926.tb00600.x"},{"key":"e_1_3_8_6_2","doi-asserted-by":"publisher","DOI":"10.5962\/bhl.title.44516"},{"key":"e_1_3_8_7_2","doi-asserted-by":"publisher","DOI":"10.5962\/bhl.title.27468"},{"key":"e_1_3_8_8_2","doi-asserted-by":"publisher","DOI":"10.1086\/286141"},{"key":"e_1_3_8_9_2","doi-asserted-by":"publisher","DOI":"10.2307\/2407858"},{"key":"e_1_3_8_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/hdy.1981.2"},{"key":"e_1_3_8_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.179.4068.90"},{"key":"e_1_3_8_12_2","doi-asserted-by":"publisher","DOI":"10.1086\/281794"},{"key":"e_1_3_8_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.156.3774.477"},{"key":"e_1_3_8_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00299371"},{"key":"e_1_3_8_15_2","first-page":"1","article-title":"The theory of sex allocation","volume":"18","author":"Charnov EL","year":"1982","unstructured":"Charnov EL. 1982 The theory of sex allocation. Monogr. Popul. Biol. 18, 1\u2013355.","journal-title":"Monogr. Popul. Biol."},{"key":"e_1_3_8_16_2","first-page":"1","article-title":"Theoretical studies on sex ratio evolution","volume":"22","author":"Karlin S","year":"1986","unstructured":"Karlin S, Lessard S. 1986 Theoretical studies on sex ratio evolution. Monogr. Popul. Biol. 22, 1\u2013313.","journal-title":"Monogr. Popul. Biol."},{"key":"e_1_3_8_17_2","doi-asserted-by":"publisher","DOI":"10.2307\/2410026"},{"key":"e_1_3_8_18_2","doi-asserted-by":"publisher","DOI":"10.1086\/285687"},{"key":"e_1_3_8_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/148.2.719"},{"key":"e_1_3_8_20_2","first-page":"277","article-title":"Rapid evolution towards equal sex ratios in a system with heterogamety","volume":"1","author":"Blows MW","year":"1999","unstructured":"Blows MW, Berrigan D, Gilchrist GW. 1999 Rapid evolution towards equal sex ratios in a system with heterogamety. Evol. Ecol. Res. 1, 277\u2013283.","journal-title":"Evol. Ecol. Res."},{"key":"e_1_3_8_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2101427118"},{"key":"e_1_3_8_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-5223.1977.tb00956.x"},{"key":"e_1_3_8_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1420-9101.2010.02129.x"},{"key":"e_1_3_8_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41437-023-00632-7"},{"key":"e_1_3_8_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.hdy.6800018"},{"key":"e_1_3_8_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1812593116"},{"key":"e_1_3_8_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.114.2955.181.b"},{"key":"e_1_3_8_28_2","doi-asserted-by":"publisher","DOI":"10.1353\/hub.2001.0015"},{"key":"e_1_3_8_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11692-008-9046-3"},{"key":"e_1_3_8_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2015.169"},{"key":"e_1_3_8_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2660(08)60288-6"},{"key":"e_1_3_8_32_2","first-page":"951","article-title":"A two-generation study of human sex-ratio variation","volume":"35","author":"Curtsinger JW","year":"1983","unstructured":"Curtsinger JW, Ito R, Hiraizumi Y. 1983 A two-generation study of human sex-ratio variation. Am. J. Hum. Genet. 35, 951\u2013961.","journal-title":"Am. J. Hum. Genet."},{"key":"e_1_3_8_33_2","doi-asserted-by":"publisher","DOI":"10.1080\/09332480.2001.10542293"},{"key":"e_1_3_8_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds304"},{"key":"e_1_3_8_35_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.290.7.929"},{"key":"e_1_3_8_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajhb.20978"},{"key":"e_1_3_8_37_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.028977"},{"key":"e_1_3_8_38_2","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.2019.2849"},{"key":"e_1_3_8_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3285"},{"key":"e_1_3_8_40_2","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.2020.2638"},{"key":"e_1_3_8_41_2","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.2020.2632"},{"key":"e_1_3_8_42_2","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.2021.0304"},{"key":"e_1_3_8_43_2","doi-asserted-by":"crossref","unstructured":"Harper KT Sidari MJ Zietsch BP. 2023 Agent-based modelling shows that operation of fisher\u2019s principle does not explain zero heritability in human offspring sex ratio. bioRxiv. (doi:10.1101\/2023.04.04.535652)","DOI":"10.1101\/2023.04.04.535652"},{"key":"e_1_3_8_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0579-z"},{"key":"e_1_3_8_45_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006711"},{"key":"e_1_3_8_46_2","doi-asserted-by":"publisher","DOI":"10.3390\/genes14061181"},{"key":"e_1_3_8_47_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2605.2011.01235.x"},{"key":"e_1_3_8_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1047-2797(03)00042-5"},{"key":"e_1_3_8_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.06.024"},{"key":"e_1_3_8_50_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz172"},{"key":"e_1_3_8_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2853-0"},{"key":"e_1_3_8_52_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-023-10015-2"},{"key":"e_1_3_8_53_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E17-08-0495"},{"key":"e_1_3_8_54_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.116.144113"},{"key":"e_1_3_8_55_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.837542"},{"key":"e_1_3_8_56_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M113.035600"},{"key":"e_1_3_8_57_2","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmx010"},{"key":"e_1_3_8_58_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13293-023-00520-z"},{"key":"e_1_3_8_59_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb1723"},{"key":"e_1_3_8_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3211"},{"key":"e_1_3_8_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3097"},{"key":"e_1_3_8_62_2","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msy228"},{"key":"e_1_3_8_63_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1019276108"},{"key":"e_1_3_8_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11396"},{"key":"e_1_3_8_65_2","unstructured":"dbGaP. 2024 WHI harmonized and imputed GWAS data. See https:\/\/www.ncbi.nlm.nih.gov\/projects\/gap\/cgi-bin\/study.cgi?study_id=phs000746.v3.p3."},{"key":"e_1_3_8_66_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-022-04822-8"},{"key":"e_1_3_8_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00846-7"},{"key":"e_1_3_8_68_2","unstructured":"Song S Zhang J. 2024 Data from: In search of the genetic variants of human sex ratio at birth: was fisher wrong about sex ratio evolution? Dryad Digital Repository. (doi:10.5061\/dryad.vdncjsz43)"},{"key":"e_1_3_8_69_2","unstructured":"Song S Zhang J. 2024 Data from: In search of the genetic variants of human sex ratio at birth: was Fisher wrong about sex ratio evolution? Figshare. (doi:10.6084\/m9.figshare.c.7477928)"}],"container-title":["Proceedings of the Royal Society B: Biological Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rspb.2024.1876","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/full-xml\/10.1098\/rspb.2024.1876","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rspb.2024.1876","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T23:07:36Z","timestamp":1729033656000},"score":1,"resource":{"primary":{"URL":"https:\/\/royalsocietypublishing.org\/doi\/10.1098\/rspb.2024.1876"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10]]},"references-count":68,"journal-issue":{"issue":"2033","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.1098\/rspb.2024.1876"],"URL":"https:\/\/doi.org\/10.1098\/rspb.2024.1876","relation":{},"ISSN":["0962-8452","1471-2954"],"issn-type":[{"value":"0962-8452","type":"print"},{"value":"1471-2954","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10]]},"assertion":[{"value":"2024-05-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-06","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"20241876"}}