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Using a new suite of generalizable analytic approaches, we examine gold-standard diagnostic ratings, scores on 66 dimensional measures of psychopathology, and measures of cognition and functioning in two different sex chromosome aneuploidies (SCAs) \u2013 Klinefelter (XXY\/KS) and XYY syndrome (n=102 and 64 vs. n=74 and 60 matched XY controls, total n=300). We focus on SCAs for their high collective prevalence, informativeness regarding differential X\u2013 vs. Y-chromosome effects, and potential relevance for normative sex differences. We show that XXY\/KS elevates rates for most psychiatric diagnoses as previously reported for XYY, but disproportionately so for anxiety disorders. Fine-mapping across all 66 traits provides a detailed profile of psychopathology in XXY\/KS which is strongly correlated with that of XYY (r=.75 across traits) and robust to ascertainment biases, but reveals: (i) a greater penetrance of XYY than KS\/XXY for most traits except mood\/anxiety problems, and (ii) a disproportionate impact of XYY vs. XXY\/KS on social problems. XXY\/KS and XXY showed a similar coupling of psychopathology with adaptive function and caregiver strain, but not IQ. This work provides new tools for deep-phenotypic comparisons of genetic disorders in psychiatry and uses these to detail unique and shared effects of the X\u2013 and Y-chromosome on human behavior.<\/jats:p>","DOI":"10.1101\/2023.06.19.23291614","type":"posted-content","created":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T15:55:19Z","timestamp":1687881319000},"source":"Crossref","is-referenced-by-count":0,"title":["X- vs. Y-Chromosome Influences on Human Behavior: A Deep Phenotypic Comparison of Psychopathology in XXY and XYY Syndromes"],"prefix":"10.64898","author":[{"given":"Lukas","family":"Schaffer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Srishti","family":"Rau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liv","family":"Clasen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allysa","family":"Warling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ethan T.","family":"Whitman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ajay","family":"Nadig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cassidy","family":"McDermott","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasia","family":"Xenophontos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Blumenthal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin","family":"Torres","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Armin","family":"Raznahan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023063004350401000_2023.06.19.23291614v1.1","doi-asserted-by":"crossref","unstructured":"Mollon J , Almasy L , Jacquemont S , Glahn DC . 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