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A Multi-Trait Association Analysis of Brain Disorders and Platelet Traits Identifies Novel Susceptibility Loci for Major Depression, Alzheimer’s and Parkinson’s Disease

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’s disease (AD) and Parkinson’s disease (PD) through epidemiological and...

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Autores principales: Tirozzi, Alfonsina, Quiccione, Miriam Shasa, Cerletti, Chiara, Donati, Maria Benedetta, de Gaetano, Giovanni, Iacoviello, Licia, Gialluisi, Alessandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9856280/
https://www.ncbi.nlm.nih.gov/pubmed/36672180
http://dx.doi.org/10.3390/cells12020245
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author Tirozzi, Alfonsina
Quiccione, Miriam Shasa
Cerletti, Chiara
Donati, Maria Benedetta
de Gaetano, Giovanni
Iacoviello, Licia
Gialluisi, Alessandro
author_facet Tirozzi, Alfonsina
Quiccione, Miriam Shasa
Cerletti, Chiara
Donati, Maria Benedetta
de Gaetano, Giovanni
Iacoviello, Licia
Gialluisi, Alessandro
author_sort Tirozzi, Alfonsina
collection PubMed
description 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’s disease (AD) and Parkinson’s 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 < 5 × 10(−8)) 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 ±10 kb, 62 genes were enriched for associations with AD, 70 with PD and 125 with MDD (p < 2.7 × 10(−6)). 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 × 10(−16)). 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.
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spelling pubmed-98562802023-01-21 A Multi-Trait Association Analysis of Brain Disorders and Platelet Traits Identifies Novel Susceptibility Loci for Major Depression, Alzheimer’s and Parkinson’s Disease Tirozzi, Alfonsina Quiccione, Miriam Shasa Cerletti, Chiara Donati, Maria Benedetta de Gaetano, Giovanni Iacoviello, Licia Gialluisi, Alessandro Cells Article 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’s disease (AD) and Parkinson’s 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 < 5 × 10(−8)) 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 ±10 kb, 62 genes were enriched for associations with AD, 70 with PD and 125 with MDD (p < 2.7 × 10(−6)). 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 × 10(−16)). 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. MDPI 2023-01-06 /pmc/articles/PMC9856280/ /pubmed/36672180 http://dx.doi.org/10.3390/cells12020245 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tirozzi, Alfonsina
Quiccione, Miriam Shasa
Cerletti, Chiara
Donati, Maria Benedetta
de Gaetano, Giovanni
Iacoviello, Licia
Gialluisi, Alessandro
A Multi-Trait Association Analysis of Brain Disorders and Platelet Traits Identifies Novel Susceptibility Loci for Major Depression, Alzheimer’s and Parkinson’s Disease
title A Multi-Trait Association Analysis of Brain Disorders and Platelet Traits Identifies Novel Susceptibility Loci for Major Depression, Alzheimer’s and Parkinson’s Disease
title_full A Multi-Trait Association Analysis of Brain Disorders and Platelet Traits Identifies Novel Susceptibility Loci for Major Depression, Alzheimer’s and Parkinson’s Disease
title_fullStr A Multi-Trait Association Analysis of Brain Disorders and Platelet Traits Identifies Novel Susceptibility Loci for Major Depression, Alzheimer’s and Parkinson’s Disease
title_full_unstemmed A Multi-Trait Association Analysis of Brain Disorders and Platelet Traits Identifies Novel Susceptibility Loci for Major Depression, Alzheimer’s and Parkinson’s Disease
title_short A Multi-Trait Association Analysis of Brain Disorders and Platelet Traits Identifies Novel Susceptibility Loci for Major Depression, Alzheimer’s and Parkinson’s Disease
title_sort multi-trait association analysis of brain disorders and platelet traits identifies novel susceptibility loci for major depression, alzheimer’s and parkinson’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9856280/
https://www.ncbi.nlm.nih.gov/pubmed/36672180
http://dx.doi.org/10.3390/cells12020245
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