{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:35:42Z","timestamp":1787067342558,"version":"build-2736575974"},"reference-count":55,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T00:00:00Z","timestamp":1639094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korean Healthcare Technology R&amp;D Project","award":["HI19C0256"],"award-info":[{"award-number":["HI19C0256"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Dementia is one of the most disabling nonmotor symptoms of Parkinson\u2019s disease (PD). However, the risk factors contributing to its development remain unclear. To investigate genetic variants associated with dementia in PD, we performed microarray genotyping based on a customized platform utilizing variants identified in previous genetic studies. Microarray genotyping was performed in 313 PD patients with dementia, 321 PD patients without dementia, and 635 healthy controls. The primary analysis was performed using a multiple logistic regression model adjusted for age and sex. SNCA single nucleotide polymorphism (SNP) rs11931074 was determined to be most significantly associated with PD (odds ratio = 0.66, 95% confidence interval = 0.56\u20130.78, p = 7.75 \u00d7 10\u22127). In the analysis performed for patients with PD only, MUL1 SNP rs3738128 (odds ratio = 2.52, 95% confidence interval = 1.68\u20133.79, p = 8.75 \u00d7 10\u22126) was found to be most significantly associated with dementia in PD. SNPs in ZHX2 and ERP29 were also associated with dementia in PD. This microarray genomic study identified new loci of MUL1 associated with dementia in PD, suggesting an essential role of mitochondrial dysfunction in the development of dementia in patients with PD.<\/jats:p>","DOI":"10.3390\/genes12121975","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T01:28:11Z","timestamp":1639358891000},"page":"1975","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Microarray Genotyping Identifies New Loci Associated with Dementia in Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5097-2340","authenticated-orcid":false,"given":"Sungyang","family":"Jo","sequence":"first","affiliation":[{"name":"Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kye Won","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Neurology, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu-si 11759, Gyeonggi-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun Su","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Hyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho-Sung","family":"Ryu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Kyungpook National University Hospital, Daegu 41944, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun Ju","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,10]]},"reference":[{"key":"ref_1","unstructured":"GBD 2015 Neurological Disorders Collaborator Group (2017). Global, regional, and national burden of neurological disorders during 1990\u20132015: A systematic analysis for the Global Burden of Disease Study 2015. Lancet Neurol., 16, 877\u2013897."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1136\/jnnp.55.3.181","article-title":"Accuracy of clinical diagnosis of idiopathic Parkinson\u2019s disease: A clinico-pathological study of 100 cases","volume":"55","author":"Hughes","year":"1992","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/nrn.2017.62","article-title":"Non-motor features of Parkinson disease","volume":"18","author":"Schapira","year":"2017","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1001\/jamaneurol.2013.2110","article-title":"Prognosis of mild cognitive impairment in early Parkinson disease: The Norwegian ParkWest study","volume":"70","author":"Pedersen","year":"2013","journal-title":"JAMA Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jns.2009.08.034","article-title":"The epidemiology of dementia associated with Parkinson disease","volume":"289","author":"Aarsland","year":"2010","journal-title":"J. Neurol. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1136\/jnnp-2013-305277","article-title":"The CamPaIGN study of Parkinson\u2019s disease: 10-year outlook in an incident population-based cohort","volume":"84","author":"Mason","year":"2013","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/S1474-4422(19)30320-5","article-title":"Identification of novel risk loci, causal insights, and heritable risk for Parkinson\u2019s disease: A meta-analysis of genome-wide association studies","volume":"18","author":"Nalls","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1001\/jamaneurol.2020.0428","article-title":"Identification of risk loci for Parkinson disease in Asians and comparison of risk between Asians and Europeans: A Genome-Wide Association Study","volume":"77","author":"Foo","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1038\/ng.485","article-title":"Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson\u2019s disease","volume":"41","author":"Satake","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1038\/ng.487","article-title":"Genome-wide association study reveals genetic risk underlying Parkinson\u2019s disease","volume":"41","author":"Schulte","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/ng.642","article-title":"Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson\u2019s disease","volume":"42","author":"Hamza","year":"2010","journal-title":"Nat. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1038\/ng.3043","article-title":"Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson\u2019s disease","volume":"46","author":"Nalls","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1038\/ng.3955","article-title":"A meta-analysis of genome-wide association studies identifies 17 new Parkinson\u2019s disease risk loci","volume":"49","author":"Chang","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"579268","DOI":"10.3389\/fneur.2020.579268","article-title":"Genomic association study for cognitive impairment in Parkinson\u2019s disease","volume":"11","author":"Park","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/S1474-4422(17)30400-3","article-title":"Investigating the genetic architecture of dementia with Lewy bodies: A two-stage genome-wide association study","volume":"17","author":"Guerreiro","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7013","DOI":"10.1038\/s41598-019-43458-2","article-title":"GBA and APOE \u03b54 associate with sporadic dementia with Lewy bodies in European genome wide association study","volume":"9","author":"Rongve","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1038\/s41588-021-00785-3","article-title":"Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture","volume":"53","author":"Chia","year":"2021","journal-title":"Nat. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1093\/brain\/awz350","article-title":"Genetic modifiers of risk and age at onset in GBA associated Parkinson\u2019s disease and Lewy body dementia","volume":"143","author":"Blauwendraat","year":"2020","journal-title":"Brain"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1007\/s00702-017-1821-9","article-title":"Dementia with Lewy bodies and Parkinson\u2019s disease-dementia: Current concepts and controversies","volume":"125","author":"Jellinger","year":"2018","journal-title":"J. Neural Transm."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2314","DOI":"10.1002\/mds.21844","article-title":"Diagnostic procedures for Parkinson\u2019s disease dementia: Recommendations from the movement disorder society task force","volume":"22","author":"Dubois","year":"2007","journal-title":"Mov. Disord."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"570","DOI":"10.3389\/fneur.2020.00570","article-title":"Genomic analysis identifies new loci associated with motor complications in Parkinson\u2019s disease","volume":"11","author":"Ryu","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s11910-018-0874-y","article-title":"The genetics of dementia with Lewy bodies: Current understanding and future directions","volume":"18","author":"Orme","year":"2018","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1038\/ng.439","article-title":"Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer\u2019s disease","volume":"41","author":"Lambert","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1001\/jama.2010.574","article-title":"Genome-wide analysis of genetic loci associated with Alzheimer disease","volume":"303","author":"Seshadri","year":"2010","journal-title":"JAMA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1038\/ng.2802","article-title":"Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer\u2019s disease","volume":"45","author":"Lambert","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/s41588-018-0311-9","article-title":"Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer\u2019s disease risk","volume":"51","author":"Jansen","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.conb.2015.10.004","article-title":"Microglial genes regulating neuroinflammation in the progression of Alzheimer\u2019s disease","volume":"36","author":"Phillips","year":"2016","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nri.2017.143","article-title":"HLA variation and disease","volume":"18","author":"Dendrou","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4161\/fly.19695","article-title":"A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3","volume":"6","author":"Cingolani","year":"2012","journal-title":"Fly"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1111\/ane.13081","article-title":"MUL1 gene polymorphisms and Parkinson\u2019s disease risk","volume":"139","author":"Taximaimaiti","year":"2019","journal-title":"Acta Neurol. Scand."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.tibs.2020.11.007","article-title":"Mitochondrial dysfunction and mitophagy in Parkinson\u2019s disease: From mechanism to therapy","volume":"46","author":"Malpartida","year":"2021","journal-title":"Trends Biochem. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.pneurobio.2018.09.003","article-title":"New insights into the complex role of mitochondria in Parkinson\u2019s disease","volume":"177","author":"Kumar","year":"2019","journal-title":"Prog. Neurobiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e01958","DOI":"10.7554\/eLife.01958","article-title":"MUL1 acts in parallel to the PINK1\/parkin pathway in regulating mitofusin and compensates for loss of PINK1\/parkin","volume":"3","author":"Yun","year":"2014","journal-title":"eLife"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Dokt\u00f3r, B., Damulewicz, M., and Pyza, E. (2019). Effects of MUL1 and PARKIN on the circadian clock, brain and behaviour in Drosophila Parkinson\u2019s disease models. BMC Neurosci., 20.","DOI":"10.1186\/s12868-019-0506-8"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"94","DOI":"10.3389\/fnins.2019.00094","article-title":"Overexpression of mitochondrial ligases reverses rotenone-induced effects in a Drosophila model of Parkinson\u2019s disease","volume":"13","author":"Damulewicz","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3645","DOI":"10.1038\/s41467-019-11636-5","article-title":"Mul1 restrains Parkin-mediated mitophagy in mature neurons by maintaining ER-mitochondrial contacts","volume":"10","author":"Puri","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.bbadis.2016.11.010","article-title":"Mitochondrial dysfunction and oxidative stress in metabolic disorders\u2014A step towards mitochondria based therapeutic strategies","volume":"1863","author":"Bhatti","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41531-018-0044-6","article-title":"Mitochondrial dysfunction within the synapses of substantia nigra neurons in Parkinson\u2019s disease","volume":"4","author":"Reeve","year":"2018","journal-title":"NPJ Parkinson\u2019s Dis."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Reddy, P.H., and Oliver, D.M. (2019). Amyloid beta and phosphorylated tau-induced defective autophagy and mitophagy in Alzheimer\u2019s disease. Cells, 8.","DOI":"10.3390\/cells8050488"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"S221","DOI":"10.1016\/S1353-8020(08)70005-1","article-title":"Neuropathology of Parkinson\u2019s disease dementia and dementia with Lewy bodies with reference to striatal pathology","volume":"13","author":"Tsuboi","year":"2007","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref_41","first-page":"1234","article-title":"Neuropathology of dementia in patients with Parkinson\u2019s disease: A systematic review of autopsy studies","volume":"90","author":"Smith","year":"2019","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7404","DOI":"10.1523\/JNEUROSCI.5841-08.2009","article-title":"ZHX2 Interacts with Ephrin-B and regulates neural progenitor maintenance in the developing cerebral cortex","volume":"29","author":"Wu","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.parkreldis.2013.06.016","article-title":"Exome sequencing in familial corticobasal degeneration","volume":"19","author":"Fekete","year":"2013","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"574339","DOI":"10.3389\/fphys.2020.574339","article-title":"The probable, possible, and novel functions of ERp29","volume":"11","author":"Brecker","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"434","DOI":"10.3390\/ijms14010434","article-title":"An involvement of oxidative stress in endoplasmic reticulum stress and its associated diseases","volume":"14","author":"Bhandary","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/S0197-4580(02)00076-3","article-title":"Protein misfolding in Alzheimer\u2019s and Parkinson\u2019s disease: Genetics and molecular mechanisms","volume":"23","author":"Forloni","year":"2002","journal-title":"Neurobiol. Aging"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1111\/nan.12260","article-title":"Unfolded protein response is activated in Lewy body dementias","volume":"42","author":"Baek","year":"2016","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s10072-019-04107-8","article-title":"Association between alpha-synuclein (SNCA) rs11931074 variability and susceptibility to Parkinson\u2019s disease: An updated meta-analysis of 41,811 patients","volume":"41","author":"Du","year":"2020","journal-title":"Neurol. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1126\/science.1090278","article-title":"\u03b1-Synuclein locus triplication causes Parkinson\u2019s disease","volume":"302","author":"Singleton","year":"2003","journal-title":"Science"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1126\/science.276.5321.2045","article-title":"Mutation in the \u03b1-synuclein gene identified in families with Parkinson\u2019s disease","volume":"276","author":"Polymeropoulos","year":"1997","journal-title":"Science"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1016\/j.pharep.2018.05.002","article-title":"Sphingosine kinase 1\/sphingosine-1-phosphate receptors dependent signalling in neurodegenerative diseases. The promising target for neuroprotection in Parkinson\u2019s disease","volume":"70","author":"Motyl","year":"2018","journal-title":"Pharmacol. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1007\/s12035-013-8622-4","article-title":"Sphingosine kinase 1 and sphingosine-1-phosphate in oxidative stress evoked by 1-methyl-4-phenylpyridinium (MPP+) in human dopaminergic neuronal cells","volume":"50","author":"Pyszko","year":"2014","journal-title":"Mol. Neurobiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1007\/s12035-020-02201-z","article-title":"Pivotal role of Fyn Kinase in Parkinson\u2019s disease and levodopa-induced dyskinesia: A novel therapeutic target?","volume":"58","author":"Angelopoulou","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/s41572-021-00280-3","article-title":"Parkinson disease-associated cognitive impairment","volume":"7","author":"Aarsland","year":"2021","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1002\/mds.28342","article-title":"Genome-wide association studies of cognitive and motor progression in Parkinson\u2019s disease","volume":"36","author":"Tan","year":"2021","journal-title":"Mov. Disord."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/12\/1975\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:45:06Z","timestamp":1760168706000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/12\/1975"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,10]]},"references-count":55,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["genes12121975"],"URL":"https:\/\/doi.org\/10.3390\/genes12121975","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,10]]}}}