{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:56:12Z","timestamp":1779324972208,"version":"3.51.4"},"posted":{"date-parts":[[2024,9,24]]},"group-title":"Genetic and Genomic Medicine","reference-count":15,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T00:00:00Z","timestamp":1727136000000},"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":[[2025,5,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Emerging evidence suggests that the genetic architecture of Alzheimer\u2019s (AD) and Parkinson\u2019s diseases (PD) risk varies across ancestries. This study seeks to explore distinct and universal genetic targets across individuals of Latino, African\/African Admixed, East Asian, and European populations by implementing Population Attributable Risk (PAR) comparisons on summary statistics from genome-wide association studies (GWAS). PAR was calculated for the most significant disease variants using summary statistics derived from select multi-ancestry GWAS meta-analyses, followed by fine-mapping analysis to validate genetic contribution of disease variants to European, African\/African Admixed, East Asian, and Latino individuals. For both AD,\n                  <jats:italic>APOE4<\/jats:italic>\n                  PAR estimates were universally high across all ancestries, with\n                  <jats:italic>TSPAN14<\/jats:italic>\n                  and\n                  <jats:italic>PICALM<\/jats:italic>\n                  emerging as other common targets. Attributable risk varied across PD-related major risk loci including variation nearby\n                  <jats:italic>GBA1<\/jats:italic>\n                  and\n                  <jats:italic>LRRK2<\/jats:italic>\n                  . In contrast,\n                  <jats:italic>SNCA, MCCC1, VPS13C<\/jats:italic>\n                  , and\n                  <jats:italic>MAPT<\/jats:italic>\n                  loci demonstrated comparable attributable risk across ancestries. This cross-ancestry evaluation of PAR reinforces the genetic heterogeneity of AD and PD. In consideration of the complex etiology of these diseases, these findings may inform the strategic prioritization of therapeutic targets and improve global health outcomes.\n                <\/jats:p>","DOI":"10.1101\/2024.09.23.24314240","type":"posted-content","created":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T02:55:19Z","timestamp":1727232919000},"source":"Crossref","is-referenced-by-count":2,"title":["Assessment of common genetic variation in Alzheimer\u2019s and Parkinson\u2019s diseases reveals global distinction in population attributable risk"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5293-0654","authenticated-orcid":false,"given":"Lietsel","family":"Jones","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catalina","family":"Cerquera-Cleves","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8722-0908","authenticated-orcid":false,"given":"Artur FS","family":"Schuh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary B","family":"Makarious","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirotaka","family":"Iwaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mike A.","family":"Nalls","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alastair J","family":"Noyce","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Global Parkinson\u2019s Genetics Program (GP2)","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelis","family":"Blauwendraat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Singleton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1198-0633","authenticated-orcid":false,"given":"Ignacio","family":"Mata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1058-3831","authenticated-orcid":false,"given":"Mark R.","family":"Cookson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Bandres-Ciga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025060122101846000_2024.09.23.24314240v3.1","doi-asserted-by":"publisher","DOI":"10.1186\/s12939-024-02212-5"},{"issue":"1","key":"2025060122101846000_2024.09.23.24314240v3.2","first-page":"226","article-title":"Genome-wide association study of Parkinson\u2019s disease in East Asians","volume":"26","year":"2017","journal-title":"Hum. Mol. Genet"},{"key":"2025060122101846000_2024.09.23.24314240v3.3","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00283-1"},{"key":"2025060122101846000_2024.09.23.24314240v3.4","doi-asserted-by":"crossref","unstructured":"Loesch DP , Horimoto ARVR , Heilbron K , et al. Characterizing the Genetic Architecture of Parkinson\u2019s Disease in Latinos [Internet]. Ann. Neurol. 2021;Available from: http:\/\/dx.doi.org\/10.1002\/ana.26153","DOI":"10.1002\/ana.26153"},{"issue":"1","key":"2025060122101846000_2024.09.23.24314240v3.5","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/s41398-021-01272-3","article-title":"Ethnic and trans-ethnic genome-wide association studies identify new loci influencing Japanese Alzheimer\u2019s disease risk","volume":"11","year":"2021","journal-title":"Transl. 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Assessing the lack of diversity in genetics research across neurodegenerative diseases: a systematic review of the GWAS Catalog and literature [Internet]. medRxiv 2024;Available from: http:\/\/dx.doi.org\/10.1101\/2024.01.08.24301007","DOI":"10.1002\/alz.13873"},{"key":"2025060122101846000_2024.09.23.24314240v3.11","doi-asserted-by":"crossref","first-page":"352","DOI":"10.3389\/fgene.2018.00352","article-title":"The Relationship Between Population Attributable Fraction and Heritability in Genetic Studies","volume":"9","year":"2018","journal-title":"Front. 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