{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T09:57:23Z","timestamp":1781085443876,"version":"3.54.1"},"reference-count":70,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T00:00:00Z","timestamp":1780790400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Biol Sex Differ"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Small differences between females and males in cognitive abilities have been consistently reported, but the factors underlying these sex differences remain unclear. Social and cultural factors are thought to play a key role, but studies on this topic have been inconclusive. Examination of genetic factors may shed some light on the mechanisms underlying cognitive sex differences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using data from the Philadelphia Neurodevelopmental Cohort, a large, general population sample of individuals aged 8 to 21\u00a0years old (N\u2009=\u20094,694), we tested for sex differences in the genetic factors (i.e., Gene\u2009\u00d7\u2009Sex interactions) underlying cognitive ability. Participants completed the Penn Computerized Neurocognitive Battery, which consists of 14 tests designed to capture accuracy and speed in five domains: 1) executive function (abstraction and mental flexibility, attention, working memory), 2) episodic memory (verbal, facial, spatial), 3) complex cognition (verbal reasoning, nonverbal reasoning, spatial processing), 4) social cognition (emotion identification, emotion differentiation, age differentiation), and 5) speed (motor, sensorimotor). Composite domain scores were derived using confirmatory factor analysis, and general accuracy (g) and speed (gs) using principal component analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Small sex differences were observed on most cognitive measures (standardized mean difference (SMD)\u2009=\u20090.061\u20130.182). Males showed significantly higher genetic variance and lower environmental variance in executive (female \u03c3\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sub>g<\/jats:sub>\n                      \u2009=\u20090.301 v. male \u03c3\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sub>g<\/jats:sub>\n                      \u2009=\u20090.598, p\u2009=\u20090.001, female \u03c3\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sub>e<\/jats:sub>\n                      \u2009=\u20090.243 v. male \u03c3\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sub>e<\/jats:sub>\n                      \u2009=\u20090.024, p\u2009=\u20090.007), and complex (female \u03c3\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sub>g<\/jats:sub>\n                      \u2009=\u20090.291 v. male \u03c3\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sub>g<\/jats:sub>\n                      \u2009=\u20090.610, p\u2009=\u20090.001, female \u03c3\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sub>e<\/jats:sub>\n                      \u2009=\u20090.259 v. male \u03c3\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sub>e<\/jats:sub>\n                      \u2009=\u20090.023, p\u2009=\u20090.006) accuracy. Females showed significantly higher genetic and lower environmental variance on complex (female \u03c3\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sub>g<\/jats:sub>\n                      \u2009=\u20090.575 v. male \u03c3\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sub>g<\/jats:sub>\n                      \u2009=\u20090.135, p\u2009=\u20090.009, female \u03c3\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sub>e<\/jats:sub>\n                      \u2009=\u20090.222 v. male \u03c3\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sub>e<\/jats:sub>\n                      \u2009=\u20090.641, p\u2009=\u20090.012) and social (female \u03c3\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sub>g<\/jats:sub>\n                      \u2009=\u20090.589 v. male \u03c3\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sub>g<\/jats:sub>\n                      \u2009=\u20090.129, p\u2009=\u20090.009, female \u03c3\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sub>e<\/jats:sub>\n                      \u2009=\u20090.236 v. male \u03c3\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sub>e<\/jats:sub>\n                      \u2009=\u20090.672, p\u2009=\u20090.012) speed. Genetic correlations between females and males were not significantly different from 1 on any cognitive measure. Altogether, our results suggest that while the same genetic factors influence cognition in females and males, the magnitude of effect of these genetic factors differs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We observed small differences between females and males on most cognitive measures, as well as sex differences in heritability on some measures. Future studies are needed to delineate how environmental, genetic, and other biological factors jointly influence cognition.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13293-026-00929-2","type":"journal-article","created":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T02:35:13Z","timestamp":1780799713000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gene\u2009\u00d7\u2009sex interactions on cognition in the Philadelphia neurodevelopmental cohort"],"prefix":"10.1186","volume":"17","author":[{"given":"Josephine","family":"Mollon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma E. M.","family":"Knowles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel R.","family":"Mathias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Rodrigue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruben C.","family":"Gur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Manuel","family":"Peralta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Weiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise B.","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armin","family":"Raznahan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel E.","family":"Gur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Blangero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Almasy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Glahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,7]]},"reference":[{"key":"929_CR1","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.conb.2016.02.007","volume":"38","author":"JS Hyde","year":"2016","unstructured":"Hyde JS. Sex and cognition: gender and cognitive functions. Curr Opin Neurobiol. 2016;38:53\u20136.","journal-title":"Curr Opin Neurobiol"},{"issue":"5220","key":"929_CR2","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1126\/science.7604277","volume":"269","author":"LV Hedges","year":"1995","unstructured":"Hedges LV, Nowell A. Sex differences in mental test scores, variability, and numbers of high-scoring individuals. Science. 1995;269(5220):41\u20135.","journal-title":"Science"},{"issue":"1","key":"929_CR3","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1037\/0033-2909.104.1.53","volume":"104","author":"JS Hyde","year":"1988","unstructured":"Hyde JS, Linn MC. Gender differences in verbal ability: a meta-analysis. Psychol Bull. 1988;104(1):53.","journal-title":"Psychol Bull"},{"key":"929_CR4","doi-asserted-by":"publisher","DOI":"10.2307\/1130467","author":"MC Linn","year":"1985","unstructured":"Linn MC, Petersen AC. Emergence and characterization of sex differences in spatial ability: a meta-analysis. Child Dev. 1985. https:\/\/doi.org\/10.2307\/1130467.","journal-title":"Child Dev"},{"issue":"2","key":"929_CR5","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1037\/0033-2909.117.2.250","volume":"117","author":"D Voyer","year":"1995","unstructured":"Voyer D, Voyer S, Bryden MP. Magnitude of sex differences in spatial abilities: a meta-analysis and consideration of critical variables. Psychol Bull. 1995;117(2):250.","journal-title":"Psychol Bull"},{"issue":"1","key":"929_CR6","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.tics.2013.10.011","volume":"18","author":"DI Miller","year":"2014","unstructured":"Miller DI, Halpern DF. The new science of cognitive sex differences. Trends Cogn Sci. 2014;18(1):37\u201345.","journal-title":"Trends Cogn Sci"},{"key":"929_CR7","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1007\/s10508-008-9460-8","volume":"39","author":"RA Lippa","year":"2010","unstructured":"Lippa RA, Collaer ML, Peters M. Sex differences in mental rotation and line angle judgments are positively associated with gender equality and economic development across 53 nations. Arch Sex Behav. 2010;39:990\u20137.","journal-title":"Arch Sex Behav"},{"issue":"3","key":"929_CR8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0057988","volume":"8","author":"G Stoet","year":"2013","unstructured":"Stoet G, Geary DC. Sex differences in mathematics and reading achievement are inversely related: within-and across-nation assessment of 10 years of PISA data. PLoS ONE. 2013;8(3):e57988.","journal-title":"PLoS ONE"},{"issue":"7","key":"929_CR9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0039904","volume":"7","author":"D Reilly","year":"2012","unstructured":"Reilly D. Gender, culture, and sex-typed cognitive abilities. PLoS ONE. 2012;7(7):e39904.","journal-title":"PLoS ONE"},{"key":"929_CR10","doi-asserted-by":"publisher","DOI":"10.2307\/2112795","author":"DP Baker","year":"1993","unstructured":"Baker DP, Jones DP. Creating gender equality: cross-national gender stratification and mathematical performance. Sociol Educ. 1993. https:\/\/doi.org\/10.2307\/2112795.","journal-title":"Sociol Educ"},{"issue":"4","key":"929_CR11","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1007\/s10508-008-9460-8","volume":"39","author":"RA Lippa","year":"2010","unstructured":"Lippa RA, Collaer ML, Peters M. Sex differences in mental rotation and line angle judgments are positively associated with gender equality and economic development across 53 nations. Arch Sex Behav. 2010;39(4):990\u20137.","journal-title":"Arch Sex Behav"},{"issue":"Suppl 3","key":"929_CR12","volume":"69","author":"D Ostatn\u00edkov\u00e1","year":"2020","unstructured":"Ostatn\u00edkov\u00e1 D, Lakato\u0161ov\u00e1 S, Babkova J, Hodosy J, Celec P. Testosterone and the brain: from cognition to autism. Physiol Res. 2020;69(Suppl 3):S403.","journal-title":"Physiol Res"},{"issue":"2","key":"929_CR13","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/j.yhbeh.2012.12.007","volume":"63","author":"DS Courvoisier","year":"2013","unstructured":"Courvoisier DS, Renaud O, Geiser C, Paschke K, Gaudy K, Jordan K. Sex hormones and mental rotation: an intensive longitudinal investigation. Horm Behav. 2013;63(2):345\u201351.","journal-title":"Horm Behav"},{"issue":"4","key":"929_CR14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006711","volume":"13","author":"T Ge","year":"2017","unstructured":"Ge T, Chen C-Y, Neale BM, Sabuncu MR, Smoller JW. Phenome-wide heritability analysis of the UK Biobank. PLoS Genet. 2017;13(4):e1006711.","journal-title":"PLoS Genet"},{"issue":"1","key":"929_CR15","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-09249-3","volume":"7","author":"S Stringer","year":"2017","unstructured":"Stringer S, Polderman TJ, Posthuma D. Majority of human traits do not show evidence for sex-specific genetic and environmental effects. Sci Rep. 2017;7(1):8688.","journal-title":"Sci Rep"},{"issue":"7","key":"929_CR16","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1038\/ng.3285","volume":"47","author":"TJ Polderman","year":"2015","unstructured":"Polderman TJ, Benyamin B, De Leeuw CA, Sullivan PF, Van Bochoven A, Visscher PM, et al. Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nat Genet. 2015;47(7):702\u20139.","journal-title":"Nat Genet"},{"issue":"2","key":"929_CR17","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1534\/genetics.116.193623","volume":"205","author":"M Traglia","year":"2017","unstructured":"Traglia M, Bseiso D, Gusev A, Adviento B, Park DS, Mefford JA, et al. Genetic mechanisms leading to sex differences across common diseases and anthropometric traits. Genetics. 2017;205(2):979\u201392.","journal-title":"Genetics"},{"issue":"1","key":"929_CR18","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-1025-x","volume":"17","author":"K Rawlik","year":"2016","unstructured":"Rawlik K, Canela-Xandri O, Tenesa A. Evidence for sex-specific genetic architectures across a spectrum of human complex traits. Genome Biol. 2016;17(1):166.","journal-title":"Genome Biol"},{"issue":"2","key":"929_CR19","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1038\/mp.2014.179","volume":"20","author":"G Desachy","year":"2015","unstructured":"Desachy G, Croen L, Torres A, Kharrazi M, Delorenze G, Windham G, et al. Increased female autosomal burden of rare copy number variants in human populations and in autism families. Mol Psychiatry. 2015;20(2):170\u20135.","journal-title":"Mol Psychiatry"},{"issue":"6","key":"929_CR20","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1002\/ajmg.b.32685","volume":"180","author":"J Martin","year":"2019","unstructured":"Martin J, Tammimies K, Karlsson R, Lu Y, Larsson H, Lichtenstein P, et al. Copy number variation and neuropsychiatric problems in females and males in the general population. Am J Med Genet B Neuropsychiatr Genet. 2019;180(6):341\u201350.","journal-title":"Am J Med Genet B Neuropsychiatr Genet"},{"issue":"10","key":"929_CR21","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005378","volume":"11","author":"TW Winkler","year":"2015","unstructured":"Winkler TW, Justice AE, Graff M, Barata L, Feitosa MF, Chu S, et al. The influence of age and sex on genetic associations with adult body size and shape: a large-scale genome-wide interaction study. PLoS Genet. 2015;11(10):e1005378.","journal-title":"PLoS Genet"},{"issue":"1","key":"929_CR22","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1093\/hmg\/ddy327","volume":"28","author":"SL Pulit","year":"2019","unstructured":"Pulit SL, Stoneman C, Morris AP, Wood AR, Glastonbury CA, Tyrrell J, et al. Meta-analysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry. Hum Mol Genet. 2019;28(1):166\u201374.","journal-title":"Hum Mol Genet"},{"issue":"1","key":"929_CR23","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52244-2","volume":"15","author":"R Shafee","year":"2024","unstructured":"Shafee R, Moraczewski D, Liu S, Mallard T, Thomas A, Raznahan A. A sex-stratified analysis of the genetic architecture of human brain anatomy. Nat Commun. 2024;15(1):8041.","journal-title":"Nat Commun"},{"issue":"12","key":"929_CR24","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.1111\/jcpp.12416","volume":"56","author":"ME Calkins","year":"2015","unstructured":"Calkins ME, Merikangas KR, Moore TM, Burstein M, Behr MA, Satterthwaite TD, et al. The Philadelphia Neurodevelopmental Cohort: constructing a deep phenotyping collaborative. J Child Psychol Psychiatry. 2015;56(12):1356\u201369. https:\/\/doi.org\/10.1111\/jcpp.12416.","journal-title":"J Child Psychol Psychiatry"},{"issue":"2","key":"929_CR25","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/j.jneumeth.2009.11.017","volume":"187","author":"RC Gur","year":"2010","unstructured":"Gur RC, Richard J, Hughett P, Calkins ME, Macy L, Bilker WB, et al. A cognitive neuroscience-based computerized battery for efficient measurement of individual differences: standardization and initial construct validation. J Neurosci Methods. 2010;187(2):254\u201362.","journal-title":"J Neurosci Methods"},{"issue":"2","key":"929_CR26","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1037\/neu0000093","volume":"29","author":"TM Moore","year":"2015","unstructured":"Moore TM, Reise SP, Gur RE, Hakonarson H, Gur RC. Psychometric properties of the Penn computerized neurocognitive battery. Neuropsychology. 2015;29(2):235.","journal-title":"Neuropsychology"},{"issue":"5","key":"929_CR27","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1016\/S0893-133X(01)00278-0","volume":"25","author":"RC Gur","year":"2001","unstructured":"Gur RC, Ragland JD, Moberg PJ, Turner TH, Bilker WB, Kohler C, et al. Computerized neurocognitive scanning:: I. Methodology and validation in healthy people. Neuropsychopharmacology. 2001;25(5):766\u201376.","journal-title":"Neuropsychopharmacology"},{"key":"929_CR28","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-018-0277-0","author":"J Mollon","year":"2018","unstructured":"Mollon J, Knowles EEM, Mathias SR, Gur R, Peralta JM, Weiner DJ, et al. Genetic influence on cognitive development between childhood and adulthood. Mol Psychiatry. 2018. https:\/\/doi.org\/10.1038\/s41380-018-0277-0.","journal-title":"Mol Psychiatry"},{"key":"929_CR29","doi-asserted-by":"publisher","DOI":"10.1192\/j.eurpsy.2021.21","volume":"64","author":"J Mollon","year":"2021","unstructured":"Mollon J, Knowles EE, Mathias SR, Rodrigue A, Moore TM, Calkins ME, et al. Genetic influences on externalizing psychopathology overlap with cognitive functioning and show developmental variation. Eur Psychiatry. 2021;64:1.","journal-title":"Eur Psychiatry"},{"key":"929_CR30","unstructured":"Muth\u00e9n B, Muth\u00e9n L. Mplus. Handbook of item response theory. Chapman and Hall\/CRC. 2017. pp. 507\u201318."},{"issue":"4","key":"929_CR31","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1002\/sim.4067","volume":"30","author":"IR White","year":"2011","unstructured":"White IR, Royston P, Wood AM. Multiple imputation using chained equations: issues and guidance for practice. Stat Med. 2011;30(4):377\u201399.","journal-title":"Stat Med"},{"key":"929_CR32","doi-asserted-by":"crossref","unstructured":"Buuren Sv, Groothuis-Oudshoorn K. mice: Multivariate imputation by chained equations in R. J statist soft. 2010,1\u201368.","DOI":"10.18637\/jss.v045.i03"},{"issue":"10","key":"929_CR33","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2016.147","volume":"6","author":"L Germine","year":"2016","unstructured":"Germine L, Robinson E, Smoller J, Calkins M, Moore T, Hakonarson H, et al. Association between polygenic risk for schizophrenia, neurocognition and social cognition across development. Transl Psychiatry. 2016;6(10):e924.","journal-title":"Transl Psychiatry"},{"issue":"1","key":"929_CR34","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s13742-015-0047-8","volume":"4","author":"CC Chang","year":"2015","unstructured":"Chang CC, Chow CC, Tellier LC, Vattikuti S, Purcell SM, Lee JJ. Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience. 2015;4(1):7.","journal-title":"Gigascience"},{"issue":"2","key":"929_CR35","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1038\/ejhg.2012.148","volume":"21","author":"L Han","year":"2013","unstructured":"Han L, Abney M. Using identity by descent estimation with dense genotype data to detect positive selection. Eur J Hum Genet. 2013;21(2):205\u201311. https:\/\/doi.org\/10.1038\/ejhg.2012.148.","journal-title":"Eur J Hum Genet"},{"key":"929_CR36","unstructured":"R Development Core Team. R: A language and environment for statistical computing. R foundation for statistical computing Vienna, Austria. 2008."},{"issue":"5","key":"929_CR37","first-page":"541","volume":"77","author":"J Blangero","year":"2005","unstructured":"Blangero J, Goring HH, Kent JW Jr, Williams JT, Peterson CP, Almasy L, et al. Quantitative trait nucleotide analysis using Bayesian model selection. Hum Biol. 2005;77(5):541\u201359.","journal-title":"Hum Biol"},{"issue":"6","key":"929_CR38","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1016\/j.ajhg.2012.10.010","volume":"91","author":"D Speed","year":"2012","unstructured":"Speed D, Hemani G, Johnson MR, Balding DJ. Improved heritability estimation from genome-wide SNPs. Am J Hum Genet. 2012;91(6):1011\u201321. https:\/\/doi.org\/10.1016\/j.ajhg.2012.10.010.","journal-title":"Am J Hum Genet"},{"issue":"47","key":"929_CR39","doi-asserted-by":"publisher","first-page":"19006","DOI":"10.1073\/pnas.1313735110","volume":"110","author":"DC Glahn","year":"2013","unstructured":"Glahn DC, Kent JW Jr., Sprooten E, Diego VP, Winkler AM, Curran JE, et al. Genetic basis of neurocognitive decline and reduced white-matter integrity in normal human brain aging. Proc Natl Acad Sci U S A. 2013;110(47):19006\u201311. https:\/\/doi.org\/10.1073\/pnas.1313735110.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"929_CR40","volume":"21","author":"L Almasy","year":"2001","unstructured":"Almasy L, Towne B, Peterson C, Blangero J. Detecting genotype\u00d7 age interaction. Genet Epidemiol. 2001;21:S1.","journal-title":"Genet Epidemiol"},{"issue":"6","key":"929_CR41","first-page":"5","volume":"65","author":"J Blangero","year":"1993","unstructured":"Blangero J. Statistical genetic approaches to human adaptability. Hum Biol. 1993;65(6):5.","journal-title":"Hum Biol"},{"key":"929_CR42","doi-asserted-by":"publisher","DOI":"10.1214\/aos\/1013699998","author":"Y Benjamini","year":"2001","unstructured":"Benjamini Y, Yekutieli D. The control of the false discovery rate in multiple testing under dependency. Ann Stat. 2001. https:\/\/doi.org\/10.1214\/aos\/1013699998.","journal-title":"Ann Stat"},{"issue":"2","key":"929_CR43","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1037\/a0026712","volume":"26","author":"RC Gur","year":"2012","unstructured":"Gur RC, Richard J, Calkins ME, Chiavacci R, Hansen JA, Bilker WB, et al. Age group and sex differences in performance on a computerized neurocognitive battery in children age 8-21. Neuropsychology. 2012;26(2):251\u201365. https:\/\/doi.org\/10.1037\/a0026712.","journal-title":"Neuropsychology"},{"issue":"1","key":"929_CR44","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1037\/0033-2909.112.1.155","volume":"112","author":"J Cohen","year":"1992","unstructured":"Cohen J. A power primer. Psychol Bull. 1992;112(1):155.","journal-title":"Psychol Bull"},{"issue":"1-2","key":"929_CR45","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1002\/jnr.23830","volume":"95","author":"RC Gur","year":"2017","unstructured":"Gur RC, Gur RE. Complementarity of sex differences in brain and behavior: from laterality to multimodal neuroimaging. J Neurosci Res. 2017;95(1\u20132):189\u201399.","journal-title":"J Neurosci Res"},{"issue":"7","key":"929_CR46","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1080\/02699931.2013.875889","volume":"28","author":"AE Thompson","year":"2014","unstructured":"Thompson AE, Voyer D. Sex differences in the ability to recognise non-verbal displays of emotion: a meta-analysis. Cogn Emot. 2014;28(7):1164\u201395.","journal-title":"Cogn Emot"},{"issue":"3","key":"929_CR47","doi-asserted-by":"publisher","DOI":"10.3390\/jintelligence13030038","volume":"13","author":"JA Hall","year":"2025","unstructured":"Hall JA, Gunnery SD, Schlegel K. Gender and accuracy in decoding affect cues: a meta-analysis. J Intell. 2025;13(3):38.","journal-title":"J Intell"},{"issue":"3","key":"929_CR48","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1037\/0033-2909.126.3.424","volume":"126","author":"EB McClure","year":"2000","unstructured":"McClure EB. A meta-analytic review of sex differences in facial expression processing and their development in infants, children, and adolescents. Psychol Bull. 2000;126(3):424.","journal-title":"Psychol Bull"},{"issue":"3","key":"929_CR49","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1017\/thg.2018.19","volume":"21","author":"V Toccaceli","year":"2018","unstructured":"Toccaceli V, Fagnani C, Eisenberg N, Alessandri G, Vitale A, Stazi MA. Adult empathy: possible gender differences in gene-environment architecture for cognitive and emotional components in a large Italian twin sample. Twin Res Hum Genet. 2018;21(3):214\u201326.","journal-title":"Twin Res Hum Genet"},{"issue":"6","key":"929_CR50","doi-asserted-by":"publisher","first-page":"1402","DOI":"10.1038\/mp.2017.122","volume":"23","author":"V Warrier","year":"2018","unstructured":"Warrier V, Grasby KL, Uzefovsky F, Toro R, Smith P, Chakrabarti B, et al. Genome-wide meta-analysis of cognitive empathy: heritability, and correlates with sex, neuropsychiatric conditions and cognition. Mol Psychiatry. 2018;23(6):1402\u20139.","journal-title":"Mol Psychiatry"},{"issue":"1","key":"929_CR51","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1177\/1754073914544408","volume":"7","author":"TM Chaplin","year":"2015","unstructured":"Chaplin TM. Gender and emotion expression: a developmental contextual perspective. Emot Rev. 2015;7(1):14\u201321.","journal-title":"Emot Rev"},{"issue":"5","key":"929_CR52","doi-asserted-by":"publisher","first-page":"1086","DOI":"10.1007\/s10964-017-0786-1","volume":"47","author":"J Van der Graaff","year":"2018","unstructured":"Van der Graaff J, Carlo G, Crocetti E, Koot HM, Branje S. Prosocial behavior in adolescence: gender differences in development and links with empathy. J Youth Adolesc. 2018;47(5):1086\u201399.","journal-title":"J Youth Adolesc"},{"issue":"1-2","key":"929_CR53","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1002\/jnr.23809","volume":"95","author":"BS McEwen","year":"2017","unstructured":"McEwen BS, Milner TA. Understanding the broad influence of sex hormones and sex differences in the brain. J Neurosci Res. 2017;95(1\u20132):24\u201339.","journal-title":"J Neurosci Res"},{"issue":"1","key":"929_CR54","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.tins.2023.09.007","volume":"47","author":"M Kundakovic","year":"2024","unstructured":"Kundakovic M, Tickerhoof M. Epigenetic mechanisms underlying sex differences in the brain and behavior. Trends Neurosci. 2024;47(1):18\u201335.","journal-title":"Trends Neurosci"},{"key":"929_CR55","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.schres.2019.12.031","volume":"218","author":"D Martin","year":"2020","unstructured":"Martin D, Croft J, Pitt A, Strelchuk D, Sullivan S, Zammit S. Systematic review and meta-analysis of the relationship between genetic risk for schizophrenia and facial emotion recognition. Schizophr Res. 2020;218:7\u201313.","journal-title":"Schizophr Res"},{"issue":"3","key":"929_CR56","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.psychres.2011.04.019","volume":"188","author":"CG Kohler","year":"2011","unstructured":"Kohler CG, Hoffman LJ, Eastman LB, Healey K, Moberg PJ. Facial emotion perception in depression and bipolar disorder: a quantitative review. Psychiatry Res. 2011;188(3):303\u20139.","journal-title":"Psychiatry Res"},{"issue":"6","key":"929_CR57","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1037\/bul0000191","volume":"145","author":"JE Lauer","year":"2019","unstructured":"Lauer JE, Yhang E, Lourenco SF. The development of gender differences in spatial reasoning: a meta-analytic review. Psychol Bull. 2019;145(6):537.","journal-title":"Psychol Bull"},{"issue":"2","key":"929_CR58","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1002\/wcs.1380","volume":"7","author":"SC Levine","year":"2016","unstructured":"Levine SC, Foley A, Lourenco S, Ehrlich S, Ratliff K. Sex differences in spatial cognition: advancing the conversation. Wiley Interdiscip Rev Cogn Sci. 2016;7(2):127\u201355.","journal-title":"Wiley Interdiscip Rev Cogn Sci"},{"issue":"3","key":"929_CR59","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.intell.2006.07.009","volume":"35","author":"SB Kaufman","year":"2007","unstructured":"Kaufman SB. Sex differences in mental rotation and spatial visualization ability: can they be accounted for by differences in working memory capacity? Intelligence. 2007;35(3):211\u201323.","journal-title":"Intelligence"},{"issue":"3","key":"929_CR60","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1111\/desc.12138","volume":"17","author":"MG Tosto","year":"2014","unstructured":"Tosto MG, Hanscombe KB, Haworth CM, Davis OS, Petrill SA, Dale PS, et al. Why do spatial abilities predict mathematical performance? Dev Sci. 2014;17(3):462\u201370.","journal-title":"Dev Sci"},{"issue":"5","key":"929_CR61","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1375\/twin.13.5.437","volume":"13","author":"E Vuoksimaa","year":"2010","unstructured":"Vuoksimaa E, Viken RJ, Hokkanen L, Tuulio-Henriksson A, Rose RJ, Kaprio J. Are there sex differences in the genetic and environmental effects on mental rotation ability? Twin Res Hum Genet. 2010;13(5):437\u201341.","journal-title":"Twin Res Hum Genet"},{"issue":"4","key":"929_CR62","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1037\/bul0000320","volume":"147","author":"D Voyer","year":"2021","unstructured":"Voyer D, Saint Aubin J, Altman K, Gallant G. Sex differences in verbal working memory: a systematic review and meta-analysis. Psychol Bull. 2021;147(4):352.","journal-title":"Psychol Bull"},{"issue":"3","key":"929_CR63","doi-asserted-by":"publisher","first-page":"P137","DOI":"10.1093\/geronb\/61.3.P137","volume":"61","author":"S Read","year":"2006","unstructured":"Read S, Pedersen NL, Gatz M, Berg S, Vuoksimaa E, Malmberg B, et al. Sex differences after all those years? Heritability of cognitive abilities in old age. J Gerontol B Psychol Sci Soc Sci. 2006;61(3):P137\u201343.","journal-title":"J Gerontol B Psychol Sci Soc Sci"},{"issue":"3","key":"929_CR64","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1037\/0021-843X.116.3.433","volume":"116","author":"BM Hicks","year":"2007","unstructured":"Hicks BM, Blonigen DM, Kramer MD, Krueger RF, Patrick CJ, Iacono WG, et al. Gender differences and developmental change in externalizing disorders from late adolescence to early adulthood: a longitudinal twin study. J Abnorm Psychol. 2007;116(3):433.","journal-title":"J Abnorm Psychol"},{"issue":"5","key":"929_CR65","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1038\/sj.mp.4001950","volume":"12","author":"SR Jaffee","year":"2007","unstructured":"Jaffee SR, Price TS. Gene\u2013environment correlations: a review of the evidence and implications for prevention of mental illness. Mol Psychiatry. 2007;12(5):432\u201342.","journal-title":"Mol Psychiatry"},{"key":"929_CR66","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2024.1340108","volume":"18","author":"MS Lafta","year":"2024","unstructured":"Lafta MS, Mwinyi J, Affatato O, Rukh G, Dang J, Andersson G, et al. Exploring sex differences: insights into gene expression, neuroanatomy, neurochemistry, cognition, and pathology. Front Neurosci. 2024;18:1340108.","journal-title":"Front Neurosci"},{"issue":"11","key":"929_CR67","doi-asserted-by":"publisher","first-page":"1791","DOI":"10.1016\/j.psyneuen.2012.03.013","volume":"37","author":"E Vuoksimaa","year":"2012","unstructured":"Vuoksimaa E, Kaprio J, Eriksson CP, Rose RJ. Pubertal testosterone predicts mental rotation performance of young adult males. Psychoneuroendocrinology. 2012;37(11):1791\u2013800.","journal-title":"Psychoneuroendocrinology"},{"issue":"5","key":"929_CR68","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1016\/j.yhbeh.2013.04.002","volume":"63","author":"AM Beltz","year":"2013","unstructured":"Beltz AM, Berenbaum SA. Cognitive effects of variations in pubertal timing: is puberty a period of brain organization for human sex-typed cognition? Horm Behav. 2013;63(5):823\u20138.","journal-title":"Horm Behav"},{"issue":"12","key":"929_CR69","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1016\/j.biopsych.2020.12.024","volume":"89","author":"J Martin","year":"2021","unstructured":"Martin J, Khramtsova EA, Goleva SB, Blokland GA, Traglia M, Walters RK, et al. Examining sex-differentiated genetic effects across neuropsychiatric and behavioral traits. Biol Psychiat. 2021;89(12):1127\u201337.","journal-title":"Biol Psychiat"},{"issue":"2","key":"929_CR70","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1007\/s10519-016-9828-9","volume":"47","author":"B Verhulst","year":"2017","unstructured":"Verhulst B. A power calculator for the classical twin design. Behav Genet. 2017;47(2):255\u201361.","journal-title":"Behav Genet"}],"container-title":["Biology of Sex Differences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13293-026-00929-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13293-026-00929-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13293-026-00929-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T09:02:52Z","timestamp":1781082172000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13293-026-00929-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,7]]},"references-count":70,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["929"],"URL":"https:\/\/doi.org\/10.1186\/s13293-026-00929-2","relation":{},"ISSN":["2042-6410"],"issn-type":[{"value":"2042-6410","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,7]]},"assertion":[{"value":"18 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Ethics approval and consent to participate\n                      The Philadelphia Neurodevelopmental Cohort (PNC) was approved by the Institutional Review Boards (IRBs) of both the Children\u2019s Hospital of Philadelphia (CHOP) and the University of Pennsylvania.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"116"}}