{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T22:00:45Z","timestamp":1789164045935,"version":"build-2803163510"},"posted":{"date-parts":[[2026,1,2]]},"group-title":"Genetic and Genomic Medicine","reference-count":32,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T00:00:00Z","timestamp":1767312000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Parkinson\u2019s disease (PD) affects females and males differently, with differences in prevalence, clinical phenotypes, and therapeutic response, suggesting that biological sex may influence the underlying molecular mechanisms of PD. The extent to which genetic factors may contribute to these differences remains largely unknown.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To investigate sex-specific autosomal genetic factors associated with PD risk.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We performed a sex-stratified autosomal GWAS meta-analysis leveraging data from the Global Parkinson\u2019s Genetics Program, the International Parkinson\u2019s Disease Genomics Consortium, the UK Biobank, and the Fox Insight Genetics Study, including a total of 226,196 individuals from different European populations: 18,145 female PD cases, 95,558 female controls, 28,747 male PD cases, and 83,746 male controls.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    We observed a high genetic correlation between the male and female PD meta-analyses (rg = 0.909, SE = 0.0403; p = 8.03E-113), and the heritability estimates were comparable between sexes (\u223c10% in males and \u223c11% in females) and similar to estimates from prior sex-combined analyses. Our sex-stratified GWAS identified 57 genome-wide significant association signals, including five novel risk loci, three of which reached genome-wide significance in males only (\n                    <jats:italic>RBM8A, ANKRD23,<\/jats:italic>\n                    and\n                    <jats:italic>CNTN4<\/jats:italic>\n                    ) and two in females only (\n                    <jats:italic>RERE<\/jats:italic>\n                    and\n                    <jats:italic>ARL6IP6<\/jats:italic>\n                    ). Of the remaining previously identified GWAS loci regions, several showed differences in effect magnitude between sexes, with the\n                    <jats:italic>GALC, RERE, ARL6IP6,<\/jats:italic>\n                    and\n                    <jats:italic>RBM8A<\/jats:italic>\n                    loci demonstrating statistically significant sex-specific effects.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Overall, PD genetic architecture appears broadly similar between females and males, but the identification of five novel loci and significant differences at select regions highlights the value of sex-stratified analyses for uncovering additional genetic contributors to PD risk beyond those detected in combined analyses.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2025.12.29.25343160","type":"posted-content","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T18:30:12Z","timestamp":1767378612000},"source":"Crossref","is-referenced-by-count":2,"title":["Shared and Sex-Specific Genetic Risk for Parkinson\u2019s Disease Risk Across European Populations"],"prefix":"10.64898","author":[{"name":"The Global Parkinson\u2019s Genetics Program (GP2)","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2390-8110","authenticated-orcid":false,"given":"Hampton L.","family":"Leonard","sequence":"additional","affiliation":[{"name":"datatecnica"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026010505250694000_2025.12.29.25343160v1.1","doi-asserted-by":"publisher","DOI":"10.1007\/s40120-024-00687-6"},{"key":"2026010505250694000_2025.12.29.25343160v1.2","doi-asserted-by":"crossref","first-page":"917","DOI":"10.3390\/brainsci12070917","article-title":"Sex differences in Parkinson\u2019s disease: From bench to bedside","volume":"12","year":"2022","journal-title":"Brain Sci"},{"key":"2026010505250694000_2025.12.29.25343160v1.3","doi-asserted-by":"publisher","DOI":"10.1111\/ane.12796"},{"key":"2026010505250694000_2025.12.29.25343160v1.4","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1093\/brain\/awad297","article-title":"Pleiotropy with sex-specific traits reveals genetic aspects of sex differences in Parkinson\u2019s disease","volume":"147","year":"2024","journal-title":"Brain"},{"key":"2026010505250694000_2025.12.29.25343160v1.5","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1002\/mds.28760","article-title":"Increased menopausal age reduces the risk of Parkinson\u2019s disease: A Mendelian randomization approach","volume":"36","year":"2021","journal-title":"Mov. 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