{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T17:18:29Z","timestamp":1789233509648,"version":"build-2803163510"},"reference-count":67,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,12]],"date-time":"2022-11-12T00:00:00Z","timestamp":1668211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AG057522"],"award-info":[{"award-number":["R01 AG057522"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Depression is common among late-onset Alzheimer\u2019s Disease (LOAD) patients. Only a few studies investigated the genetic variability underlying the comorbidity of depression in LOAD. Moreover, the epigenetic and transcriptomic factors that may contribute to comorbid depression in LOAD have yet to be studied. Using transcriptomic and DNA-methylomic datasets from the ROSMAP cohorts, we investigated differential gene expression and DNA-methylation in LOAD patients with and without comorbid depression. Differential expression analysis did not reveal significant association between differences in gene expression and the risk of depression in LOAD. Upon sex-stratification, we identified 25 differential expressed genes (DEG) in males, of which CHI3L2 showed the strongest upregulation, and only 3 DEGs in females. Additionally, testing differences in DNA-methylation found significant hypomethylation of CpG (cg20442550) on chromosome 17 (log2FC = \u22120.500, p = 0.004). Sex-stratified differential DNA-methylation analysis did not identify any significant CpG probes. Integrating the transcriptomic and DNA-methylomic datasets did not discover relationships underlying the comorbidity of depression and LOAD. Overall, our study is the first multi-omics genome-wide exploration of the role of gene expression and epigenome alterations in the risk of comorbid depression in LOAD patients. Furthermore, we discovered sex-specific differences in gene expression underlying the risk of depression symptoms in LOAD.<\/jats:p>","DOI":"10.3390\/biom12111679","type":"journal-article","created":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T02:33:10Z","timestamp":1668393190000},"page":"1679","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Differential Gene Expression and DNA Methylation in the Risk of Depression in LOAD Patients"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8242-3052","authenticated-orcid":false,"given":"Suraj","family":"Upadhya","sequence":"first","affiliation":[{"name":"Division of Translational Brain Sciences, Department of Neurology, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Gingerich","sequence":"additional","affiliation":[{"name":"Division of Translational Brain Sciences, Department of Neurology, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael William","family":"Lutz","sequence":"additional","affiliation":[{"name":"Division of Translational Brain Sciences, Department of Neurology, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2529-8785","authenticated-orcid":false,"given":"Ornit","family":"Chiba-Falek","sequence":"additional","affiliation":[{"name":"Division of Translational Brain Sciences, Department of Neurology, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"691","DOI":"10.3233\/JAD-215061","article-title":"A Comparison of Behavioral and Psychological Symptoms of Dementia (BPSD) and BPSD Sub-Syndromes in Early-Onset and Late-Onset Alzheimer\u2019s Disease","volume":"85","author":"Altomari","year":"2022","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.3233\/JAD-170697","article-title":"The Progression of Neuropsychiatric Symptoms in Alzheimer\u2019s Disease during a Five-Year Follow-Up: Kuopio ALSOVA Study","volume":"61","author":"Hallikainen","year":"2018","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"832199","DOI":"10.3389\/fneur.2022.832199","article-title":"Neuropsychiatric or Behavioral and Psychological Symptoms of Dementia (BPSD): Focus on Prevalence and Natural History in Alzheimer\u2019s Disease and Frontotemporal Dementia","volume":"13","author":"Bruno","year":"2022","journal-title":"Front. Neurol."},{"key":"ref_4","first-page":"155","article-title":"Neuropsychiatric Symptoms in Dementia: Overview and Measurement Challenges","volume":"2","author":"Lyketsos","year":"2015","journal-title":"J. Prev. Alzheimer\u2019s Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.jalz.2011.05.2410","article-title":"Neuropsychiatric symptoms in Alzheimer\u2019s disease","volume":"7","author":"Lyketsos","year":"2011","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1212\/WNL.0000000000001238","article-title":"\u201cNoncognitive\u201d symptoms of early Alzheimer disease: A longitudinal analysis","volume":"84","author":"Masters","year":"2015","journal-title":"Neurology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.jad.2015.09.069","article-title":"The prevalence of neuropsychiatric symptoms in Alzheimer\u2019s disease: Systematic review and meta-analysis","volume":"190","author":"Zhao","year":"2016","journal-title":"J. Affect. Disord."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1002\/gps.5418","article-title":"Alzheimer\u2019s disease biomarkers as predictors of trajectories of depression and apathy in cognitively normal individuals, mild cognitive impairment, and Alzheimer\u2019s disease dementia","volume":"36","author":"Banning","year":"2021","journal-title":"Int. J. Geriatr. Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/s41398-020-0769-y","article-title":"Shared genetic etiology underlying Alzheimer\u2019s disease and major depressive disorder","volume":"10","author":"Lutz","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"827447","DOI":"10.3389\/fnins.2022.827447","article-title":"Polygenic Risk Score Effectively Predicts Depression Onset in Alzheimer\u2019s Disease Based on Major Depressive Disorder Risk Variants","volume":"16","author":"Upadhya","year":"2022","journal-title":"Front. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1038\/s41593-019-0539-4","article-title":"A single-cell atlas of entorhinal cortex from individuals with Alzheimer\u2019s disease reveals cell-type-specific gene expression regulation","volume":"22","author":"Grubman","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/s41514-020-00052-5","article-title":"Differential transcript usage unravels gene expression alterations in Alzheimer\u2019s disease human brains","volume":"7","author":"Iohan","year":"2021","journal-title":"npj Aging Mech. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"633","DOI":"10.3389\/fnins.2019.00633","article-title":"Meta-Analysis of Gene Expression and Identification of Biological Regulatory Mechanisms in Alzheimer\u2019s Disease","volume":"13","author":"Su","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1038\/nn.3786","article-title":"Alzheimer\u2019s disease: Early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci","volume":"17","author":"Srivastava","year":"2014","journal-title":"Nat. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6114","DOI":"10.1038\/s41467-020-19791-w","article-title":"Epigenome-wide meta-analysis of DNA methylation differences in prefrontal cortex implicates the immune processes in Alzheimer\u2019s disease","volume":"11","author":"Zhang","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1097\/YPG.0000000000000309","article-title":"Brain differential gene expression and blood cross-validation of a molecular signature of patients with major depressive disorder","volume":"32","author":"Bustillo","year":"2022","journal-title":"Psychiatr. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1038\/mp.2015.57","article-title":"Gene expression in major depressive disorder","volume":"21","author":"Jansen","year":"2016","journal-title":"Mol. Psychiatry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"549","DOI":"10.4103\/psychiatry.IndianJPsychiatry_858_20","article-title":"Transcriptomics and sequencing analysis of gene expression profiling for major depressive disorder","volume":"63","author":"Verma","year":"2021","journal-title":"Indian J. Psychiatry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.biopsych.2020.05.006","article-title":"Major Depressive Disorder Is Associated With Differential Expression of Innate Immune and Neutrophil-Related Gene Networks in Peripheral Blood: A Quantitative Review of Whole-Genome Transcriptional Data From Case-Control Studies","volume":"88","author":"Wittenberg","year":"2020","journal-title":"Biol. Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/s41398-021-01506-4","article-title":"No evidence for differential gene expression in major depressive disorder PBMCs, but robust evidence of elevated biological ageing","volume":"11","author":"Cole","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1001\/jamapsychiatry.2018.1725","article-title":"DNA Methylation Signatures of Depressive Symptoms in Middle-aged and Elderly Persons: Meta-analysis of Multiethnic Epigenome-wide Studies","volume":"75","author":"Nedeljkovic","year":"2018","journal-title":"JAMA Psychiatry"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S161","DOI":"10.3233\/JAD-179939","article-title":"Religious Orders Study and Rush Memory and Aging Project","volume":"64","author":"Bennett","year":"2018","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"628","DOI":"10.2174\/156720512801322573","article-title":"Overview and findings from the religious orders study","volume":"9","author":"Bennett","year":"2012","journal-title":"Curr. Alzheimer Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"646","DOI":"10.2174\/156720512801322663","article-title":"Overview and findings from the rush Memory and Aging Project","volume":"9","author":"Bennett","year":"2012","journal-title":"Curr. Alzheimer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1097\/00019442-200403000-00012","article-title":"Cerebral infarctions and the relationship of depression symptoms to level of cognitive functioning in older persons","volume":"12","author":"Bennett","year":"2004","journal-title":"Am. J. Geriatr. Psychiatry"},{"key":"ref_26","unstructured":"Association, A.P. (1987). Diagnostic and Statistical Manual of Mental Disorders, American Psychiatric Publishing. [3rd ed.]."},{"key":"ref_27","first-page":"Cd010783","article-title":"Mini-Mental State Examination (MMSE) for the detection of Alzheimer\u2019s disease and other dementias in people with mild cognitive impairment (MCI)","volume":"2015","author":"Smailagic","year":"2015","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1038\/s41593-018-0154-9","article-title":"A molecular network of the aging human brain provides insights into the pathology and cognitive decline of Alzheimer\u2019s disease","volume":"21","author":"Mostafavi","year":"2018","journal-title":"Nat. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B (Methodol.)"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Du, P., Zhang, X., Huang, C.-C., Jafari, N., Kibbe, W.A., Hou, L., and Lin, S.M. (2010). Comparison of Beta-value and M-value methods for quantifying methylation levels by microarray analysis. BMC Bioinform., 11.","DOI":"10.1186\/1471-2105-11-587"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1101\/gr.229102","article-title":"The human genome browser at UCSC","volume":"12","author":"Kent","year":"2002","journal-title":"Genome Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1093\/hmg\/ddr034","article-title":"Impairment of the tRNA-splicing endonuclease subunit 54 (tsen54) gene causes neurological abnormalities and larval death in zebrafish models of pontocerebellar hypoplasia","volume":"20","author":"Kasher","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Kwan, J.J., and Donaldson, L.W. (2016). A lack of peptide binding and decreased thermostability suggests that the CASKIN2 scaffolding protein SH3 domain may be vestigial. BMC Struct. Biol., 16.","DOI":"10.1186\/s12900-016-0065-5"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s13195-018-0455-y","article-title":"Heterogeneity of Alzheimer\u2019s disease: Consequence for drug trials?","volume":"10","author":"Devi","year":"2018","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3058","DOI":"10.18632\/aging.101638","article-title":"The heterogeneity within Alzheimer\u2019s disease","volume":"10","author":"Ferreira","year":"2018","journal-title":"Aging (Albany NY)"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Komarova, N.L., and Thalhauser, C.J. (2011). High degree of heterogeneity in Alzheimer\u2019s disease progression patterns. PLoS Comput. Biol., 7.","DOI":"10.1371\/journal.pcbi.1002251"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/alzrt155","article-title":"Clinical, imaging, and pathological heterogeneity of the Alzheimer\u2019s disease syndrome","volume":"5","author":"Lam","year":"2013","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"102353","DOI":"10.1016\/j.pneurobio.2022.102353","article-title":"Chromosomal and environmental contributions to sex differences in the vulnerability to neurological and neuropsychiatric disorders: Implications for therapeutic interventions","volume":"219","author":"Pallier","year":"2022","journal-title":"Prog. Neurobiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1503\/jpn.150205","article-title":"Why is depression more prevalent in women?","volume":"40","author":"Albert","year":"2015","journal-title":"J. Psychiatry Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"589687","DOI":"10.3389\/fpsyt.2021.589687","article-title":"A Hypothesis of Gender Differences in Self-Reporting Symptom of Depression: Implications to Solve Under-Diagnosis and Under-Treatment of Depression in Males","volume":"12","author":"Shi","year":"2021","journal-title":"Front. Psychiatry"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"dmm045211","DOI":"10.1242\/dmm.045211","article-title":"Sex-dependent effect of APOE on Alzheimer\u2019s disease and other age-related neurodegenerative disorders","volume":"13","author":"Gamache","year":"2020","journal-title":"Dis. Model. Mech."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"437","DOI":"10.31887\/DCNS.2016.18.4\/cepperson","article-title":"Considering sex and gender in Alzheimer disease and other dementias","volume":"18","author":"Podcasy","year":"2016","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s13195-022-00991-z","article-title":"Sex differences in neuropsychiatric symptoms in Alzheimer\u2019s disease dementia: A meta-analysis","volume":"14","author":"Eikelboom","year":"2022","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"611038","DOI":"10.3389\/fonc.2021.611038","article-title":"CHI3L2 Is a Novel Prognostic Biomarker and Correlated With Immune Infiltrates in Gliomas","volume":"11","author":"Liu","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s12974-020-1723-x","article-title":"Frontal cortex chitinase and pentraxin neuroinflammatory alterations during the progression of Alzheimer\u2019s disease","volume":"17","author":"Perez","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"850","DOI":"10.4103\/1673-5374.268971","article-title":"Neurodegenerative diseases as proteinopathies-driven immune disorders","volume":"15","author":"Ciccocioppo","year":"2020","journal-title":"Neural Regen. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1007\/s40473-020-00207-4","article-title":"Inflammatory Pathways in Psychiatric Disorders: The case of Schizophrenia and Depression","volume":"7","author":"Feng","year":"2020","journal-title":"Curr. Behav. Neurosci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1001\/jamapsychiatry.2022.0407","article-title":"Inflammation and Brain Structure in Schizophrenia and Other Neuropsychiatric Disorders: A Mendelian Randomization Study","volume":"79","author":"Williams","year":"2022","journal-title":"JAMA Psychiatry"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1007\/s12031-020-01667-9","article-title":"CHI3L2 Expression Levels Are Correlated with AIF1, PECAM1, and CALB1 in the Brains of Alzheimer\u2019s Disease Patients","volume":"70","author":"Sanfilippo","year":"2020","journal-title":"J. Mol. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e538","DOI":"10.1038\/tp.2015.9","article-title":"RNA expression profiling in depressed patients suggests retinoid-related orphan receptor alpha as a biomarker for antidepressant response","volume":"5","author":"Hennings","year":"2015","journal-title":"Transl. Psychiatry"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/j.tcb.2018.05.005","article-title":"The Role of Xist in X-Chromosome Dosage Compensation","volume":"28","author":"Sahakyan","year":"2018","journal-title":"Trends Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/j.ebiom.2015.06.012","article-title":"Over-expression of XIST, the Master Gene for X Chromosome Inactivation, in Females With Major Affective Disorders","volume":"2","author":"Ji","year":"2015","journal-title":"eBioMedicine"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"499","DOI":"10.2174\/1567205017666200807185624","article-title":"LncRNA Xist, X-chromosome Instability and Alzheimer\u2019s Disease","volume":"17","author":"Chanda","year":"2020","journal-title":"Curr. Alzheimer Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1080\/01677063.2022.2028784","article-title":"lncRNA XIST induces A\u03b2 accumulation and neuroinflammation by the epigenetic repression of NEP in Alzheimer\u2019s disease","volume":"36","author":"Yan","year":"2022","journal-title":"J. Neurogenet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1002\/cbin.11263","article-title":"Silencing of long noncoding RNA XIST attenuated Alzheimer\u2019s disease-related BACE1 alteration through miR-124","volume":"44","author":"Yue","year":"2020","journal-title":"Cell Biol. Int."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"268","DOI":"10.3389\/fgene.2019.00268","article-title":"Epigenetic Regulations in Neuropsychiatric Disorders","volume":"10","author":"Kuehner","year":"2019","journal-title":"Front. Genet."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/s41392-022-01078-9","article-title":"The role of histone modifications: From neurodevelopment to neurodiseases","volume":"7","author":"Park","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e12244","DOI":"10.1002\/trc2.12244","article-title":"Bioinformatics pipeline to guide late-onset Alzheimer\u2019s disease (LOAD) post-GWAS studies: Prioritizing transcription regulatory variants within LOAD-associated regions","volume":"8","author":"Lutz","year":"2022","journal-title":"Alzheimer\u2019s Dement (N. Y.)"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/s41398-021-01493-6","article-title":"Transcriptional-regulatory convergence across functional MDD risk variants identified by massively parallel reporter assays","volume":"11","author":"Mulvey","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s13024-021-00496-7","article-title":"The promise of microRNA-based therapies in Alzheimer\u2019s disease: Challenges and perspectives","volume":"16","author":"Walgrave","year":"2021","journal-title":"Mol. Neurodegener."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"8200","DOI":"10.1523\/JNEUROSCI.0902-18.2018","article-title":"A Novel Alternative Splicing Mechanism That Enhances Human 5-HT1A Receptor RNA Stability Is Altered in Major Depression","volume":"38","author":"Zhang","year":"2018","journal-title":"J. Neurosci."},{"key":"ref_63","first-page":"6","article-title":"Alternative Splicing in Alzheimer\u2019s Disease","volume":"2","author":"Love","year":"2015","journal-title":"J. Parkinsons Dis. Alzheimers Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e037712","DOI":"10.1002\/alz.037712","article-title":"Cell-type-specific and sex-dependent changes in the chromatin accessibility landscape in late-onset Alzheimer\u2019s disease brains","volume":"16","author":"Barrera","year":"2020","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/s41398-020-00948-6","article-title":"Association between DNA methylation levels in brain tissue and late-life depression in community-based participants","volume":"10","author":"Robins","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13148-017-0320-z","article-title":"An empirically driven data reduction method on the human 450K methylation array to remove tissue specific non-variable CpGs","volume":"9","author":"Edgar","year":"2017","journal-title":"Clin. Epigenetics"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Lauber, C., Gerl, M.J., Klose, C., Ottosson, F., Melander, O., and Simons, K. (2022). Lipidomic risk scores are independent of polygenic risk scores and can predict incidence of diabetes and cardiovascular disease in a large population cohort. 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