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Dementia"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>DNA microarray\u2010based studies report differentially methylated positions (DMPs) in blood between late\u2010onset dementia due to Alzheimer's disease (AD) and cognitively unimpaired individuals, but interrogate &lt; 4% of the genome.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We used whole genome methylation sequencing (WGMS) to quantify DNA methylation levels at\u00a025,409,826\u00a0CpG loci in\u00a0281 blood samples from 108 AD and 173\u00a0cognitively unimpaired\u00a0individuals.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>WGMS identified 28,038 DMPs throughout the human methylome, including 2707 differentially methylated genes\u00a0(e.g.,\u00a0<jats:italic>SORCS3<\/jats:italic>,\u00a0<jats:italic>GABA<\/jats:italic>, and\u00a0<jats:italic>PICALM<\/jats:italic>)\u00a0encoding proteins\u00a0in biological pathways relevant to AD such as\u00a0synaptic membrane, cation channel complex, and glutamatergic synapse.\u00a0One hundred seventy\u2010three differentially methylated blood\u2010specific enhancers interact with the promoters of 95 genes that are differentially expressed in blood from persons with and without AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>WGMS identifies differentially methylated CpGs in known and newly detected genes and enhancers in blood from persons with and without AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Whole genome DNA methylation levels were quantified in blood from persons with and without Alzheimer's disease (AD).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Twenty\u2010eight thousand thirty\u2010eight differentially methylated positions (DMPs) were identified.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Two thousand seven hundred seven genes comprise DMPs.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Forty\u2010eight of 75 independent genetic risk loci for AD have DMPs.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>One thousand five hundred sixty\u2010eight blood\u2010specific enhancers comprise DMPs, 173 of which interact with the promoters of 95 genes that are differentially expressed in blood from persons with and without AD.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.13514","type":"journal-article","created":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T12:50:30Z","timestamp":1697719830000},"page":"1050-1062","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Whole genome methylation sequencing in blood identifies extensive differential DNA methylation in late\u2010onset dementia due to Alzheimer's disease"],"prefix":"10.1002","volume":"20","author":[{"given":"Coleman","family":"Breen","sequence":"first","affiliation":[{"name":"Department of Statistics University of Wisconsin, Medical Sciences Center  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ligia A.","family":"Papale","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay R.","family":"Clark","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"},{"name":"Geriatric Research Education and Clinical Center William S. 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