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(PRS) to discover associations with novel rare variants (RVs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      PRSs for European ancestry (EA) participants of the Alzheimer's Disease Sequencing Project were calculated using summary statistics from a large genome\u2010wide association study. Participants were classified into high (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a05738) and low (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a05324) PRS groups based on the median PRS and on the lower and upper 35% of the PRS distribution.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Risk variants were disproportionately enriched in the low\u2010PRS group, while protective ones were disproportionately enriched in the high\u2010PRS group. Genome\u2010wide significant (GWS) associations for increased AD risk were identified with RVs spanning a 3.5\u2010Mb region on chromosome 14. GWS protective variants in\n                      <jats:italic>ALDH9A1<\/jats:italic>\n                      ,\n                      <jats:italic>BICC1<\/jats:italic>\n                      , and\n                      <jats:italic>PAN3<\/jats:italic>\n                      were identified in the upper 35% PRS group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Our findings provide unique opportunities to study RVs whose effects are opposite to the risk conferred by the genetic background.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71710","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T08:01:49Z","timestamp":1786003309000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Stratification by a polygenic risk score of common variation aids in Alzheimer's disease rare variant discovery"],"prefix":"10.1002","volume":"22","author":[{"given":"Oluwatosin","family":"Olayinka","sequence":"first","affiliation":[{"name":"Bioinformatics Program Boston University  Boston Massachusetts USA"},{"name":"Department of Medicine (Biomedical Genetics) Boston University Chobanian &amp; Avedisian School of Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.","family":"Farrell","sequence":"additional","affiliation":[{"name":"Department of Medicine (Biomedical Genetics) Boston University Chobanian &amp; Avedisian School of Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congcong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Medicine (Biomedical Genetics) Boston University Chobanian &amp; Avedisian School of Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zainab","family":"Khurshid","sequence":"additional","affiliation":[{"name":"Bioinformatics Program Boston University  Boston Massachusetts USA"},{"name":"Department of Medicine (Biomedical Genetics) Boston University Chobanian &amp; Avedisian School of Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Alzheimer's Disease Sequencing Project","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eden R.","family":"Martin","sequence":"additional","affiliation":[{"name":"John P. 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