{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T22:09:22Z","timestamp":1794262162785,"version":"4.9.0"},"posted":{"date-parts":[[2023,12,24]]},"group-title":"Genetic and Genomic Medicine","reference-count":54,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,12,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  DNA methylation (DNAm) is an epigenetic mark with essential roles in disease development and predisposition. Here, we created genome-wide maps of methylation quantitative trait loci (meQTL) in three peripheral tissues and used Mendelian randomization (MR) analyses to assess the potential causal relationships between DNAm and risk for two common neurodegenerative disorders, i.e. Alzheimer\u2019s disease (AD) and Parkinson\u2019s disease (PD). Genome-wide single nucleotide polymorphism (SNP; \u223c5.5M sites) and DNAm (\u223c850K CpG sites) data were generated from whole blood (n=1,058), buccal (n=1,527) and saliva (n=837) specimens. We identified between 11 and 15 million genome-wide significant (p&lt;10\n                  <jats:sup>-14<\/jats:sup>\n                  ) SNP-CpG associations in each tissue. Combining these meQTL GWAS results with recent AD\/PD GWAS summary statistics by MR strongly suggests that the previously described associations between\n                  <jats:italic>PSMC3<\/jats:italic>\n                  ,\n                  <jats:italic>PICALM<\/jats:italic>\n                  , and\n                  <jats:italic>TSPAN14<\/jats:italic>\n                  and AD may be founded on differential DNAm in or near these genes. In addition, there is strong, albeit less unequivocal, support for causal links between DNAm at\n                  <jats:italic>PRDM7<\/jats:italic>\n                  in AD as well as at\n                  <jats:italic>KANSL1\/MAPT<\/jats:italic>\n                  in AD and PD. Our study adds valuable insights on AD\/PD pathogenesis by combining two high-resolution \u201comics\u201d domains, and the meQTL data shared along with this publication will allow like-minded analyses in other diseases.\n                <\/jats:p>","DOI":"10.1101\/2023.12.22.23300365","type":"posted-content","created":{"date-parts":[[2023,12,24]],"date-time":"2023-12-24T13:00:10Z","timestamp":1703422810000},"source":"Crossref","is-referenced-by-count":10,"title":["Genome-wide QTL mapping across three tissues highlights several Alzheimer\u2019s and Parkinson\u2019s disease loci potentially acting via DNA methylation"],"prefix":"10.64898","author":[{"given":"Olena","family":"Ohlei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmine","family":"Sommerer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerija","family":"Dobricic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Homann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Deecke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"Schilling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Bartr\u00e9s-Faz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Cattaneo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"D\u00fczel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders M.","family":"Fjell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulman","family":"Lindenberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1lvaro","family":"Pascual-Leone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanaz Sedghpour","family":"Sabet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Sol\u00e9-Padull\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep M.","family":"Tormos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentin M.","family":"Vetter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine B.","family":"Walhovd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Wesse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Wittig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Franke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilja","family":"Demuth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina M.","family":"Lill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Bertram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"issue":"54","key":"2023122810400679000_2023.12.22.23300365v1.1","first-page":"412","article-title":"New insights into the genetic etiology of Alzheimer\u2019s disease and related dementias","volume":"544","year":"2022","journal-title":"Nat. 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