{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:33:45Z","timestamp":1791923625727,"version":"4.3.4"},"reference-count":68,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:00:00Z","timestamp":1672963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["F\/080032\/01\/X35"],"award-info":[{"award-number":["F\/080032\/01\/X35"]}]},{"name":"Italian Ministry of Health","award":["F24I19000630008"],"award-info":[{"award-number":["F24I19000630008"]}]},{"name":"Italian Ministry of Economic Development","award":["F\/080032\/01\/X35"],"award-info":[{"award-number":["F\/080032\/01\/X35"]}]},{"name":"Italian Ministry of Economic Development","award":["F24I19000630008"],"award-info":[{"award-number":["F24I19000630008"]}]},{"name":"Italian National Institute for Insurance against Accidents at Work","award":["F\/080032\/01\/X35"],"award-info":[{"award-number":["F\/080032\/01\/X35"]}]},{"name":"Italian National Institute for Insurance against Accidents at Work","award":["F24I19000630008"],"award-info":[{"award-number":["F24I19000630008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Among candidate neurodegenerative\/neuropsychiatric risk-predictive biomarkers, platelet count, mean platelet volume and platelet distribution width have been associated with the risk of major depressive disorder (MDD), Alzheimer\u2019s disease (AD) and Parkinson\u2019s disease (PD) through epidemiological and genomic studies, suggesting partial co-heritability. We exploited these relationships for a multi-trait association analysis, using publicly available summary statistics of genome-wide association studies (GWASs) of all traits reported above. Gene-based enrichment tests were carried out, as well as a network analysis of significantly enriched genes. We analyzed 4,540,326 single nucleotide polymorphisms shared among the analyzed GWASs, observing 149 genome-wide significant multi-trait LD-independent associations (p &lt; 5 \u00d7 10\u22128) for AD, 70 for PD and 139 for MDD. Among these, 27 novel associations were detected for AD, 34 for PD and 40 for MDD. Out of 18,781 genes with annotated variants within \u00b110 kb, 62 genes were enriched for associations with AD, 70 with PD and 125 with MDD (p &lt; 2.7 \u00d7 10\u22126). Of these, seven genes were novel susceptibility loci for AD (EPPK1, TTLL1, PACSIN2, TPM4, PIF1, ZNF689, AZGP1P1), two for PD (SLC26A1, EFNA3) and two for MDD (HSPH1, TRMT61A). The resulting network showed a significant excess of interactions (enrichment p = 1.0 \u00d7 10\u221216). The novel genes that were identified are involved in the organization of cytoskeletal architecture (EPPK1, TTLL1, PACSIN2, TPM4), telomere shortening (PIF1), the regulation of cellular aging (ZNF689, AZGP1P1) and neurodevelopment (EFNA3), thus, providing novel insights into the shared underlying biology of brain disorders and platelet parameters.<\/jats:p>","DOI":"10.3390\/cells12020245","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T03:25:58Z","timestamp":1673234758000},"page":"245","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["A Multi-Trait Association Analysis of Brain Disorders and Platelet Traits Identifies Novel Susceptibility Loci for Major Depression, Alzheimer\u2019s and Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6052-1807","authenticated-orcid":false,"given":"Alfonsina","family":"Tirozzi","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Prevention, IRCCS Neuromed, Via dell\u2019Elettronica, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam Shasa","family":"Quiccione","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Prevention, IRCCS Neuromed, Via dell\u2019Elettronica, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4759-3179","authenticated-orcid":false,"given":"Chiara","family":"Cerletti","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Prevention, IRCCS Neuromed, Via dell\u2019Elettronica, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Benedetta","family":"Donati","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Prevention, IRCCS Neuromed, Via dell\u2019Elettronica, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7823-1402","authenticated-orcid":false,"given":"Giovanni","family":"de Gaetano","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Prevention, IRCCS Neuromed, Via dell\u2019Elettronica, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0514-5885","authenticated-orcid":false,"given":"Licia","family":"Iacoviello","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Prevention, IRCCS Neuromed, Via dell\u2019Elettronica, 86077 Pozzilli, Italy"},{"name":"EPIMED Research Center, Department of Medicine and Surgery, University of Insubria, Via Ravasi 2, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7388-4463","authenticated-orcid":false,"given":"Alessandro","family":"Gialluisi","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Prevention, IRCCS Neuromed, Via dell\u2019Elettronica, 86077 Pozzilli, Italy"},{"name":"EPIMED Research Center, Department of Medicine and Surgery, University of Insubria, Via Ravasi 2, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1002\/rth2.12254","article-title":"Blood platelets: Circulating mirrors of neurons?","volume":"3","author":"Canobbio","year":"2019","journal-title":"Res. 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