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CATALOGO DEI PRODOTTI DELLA RICERCA
Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement
genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility,
including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in ,2,100 genes of
cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733
controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative
novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through which the novel
variants could affect CAD risk were explored through association tests with vascular risk factors and gene expression. We
confirmed associations of several previously known CAD susceptibility loci (eg, 9p21.3:p,10233; LPA:p,10219;
1p13.3:p,10217) as well as three recently discovered loci (COL4A1/COL4A2, ZC3HC1, CYP17A1:p,561027). However, we
found essentially null results for most previously suggested CAD candidate genes. In our replication study of 24 promising
common variants, we identified novel associations of variants in or near LIPA, IL5, TRIB1, and ABCG5/ABCG8, with per-allele
odds ratios for CAD risk with each of the novel variants ranging from 1.06–1.09. Associations with variants at LIPA, TRIB1, and
ABCG5/ABCG8 were supported by gene expression data or effects on lipid levels. Apart from the previously reported variants
in LPA, none of the other ,4,500 low frequency and functional variants showed a strong effect. Associations in South Asians
did not differ appreciably from those in Europeans, except for 9p21.3 (per-allele odds ratio: 1.14 versus 1.27 respectively; P
for heterogeneity = 0.003). This large-scale gene-centric analysis has identified several novel genes for CAD that relate to
diverse biochemical and cellular functions and clarified the literature with regard to many previously suggested genes.
Large-scale gene-centric analysis identifies novelvariants for coronary artery disease.
Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement
genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility,
including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in ,2,100 genes of
cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733
controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative
novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through which the novel
variants could affect CAD risk were explored through association tests with vascular risk factors and gene expression. We
confirmed associations of several previously known CAD susceptibility loci (eg, 9p21.3:p,10233; LPA:p,10219;
1p13.3:p,10217) as well as three recently discovered loci (COL4A1/COL4A2, ZC3HC1, CYP17A1:p,561027). However, we
found essentially null results for most previously suggested CAD candidate genes. In our replication study of 24 promising
common variants, we identified novel associations of variants in or near LIPA, IL5, TRIB1, and ABCG5/ABCG8, with per-allele
odds ratios for CAD risk with each of the novel variants ranging from 1.06–1.09. Associations with variants at LIPA, TRIB1, and
ABCG5/ABCG8 were supported by gene expression data or effects on lipid levels. Apart from the previously reported variants
in LPA, none of the other ,4,500 low frequency and functional variants showed a strong effect. Associations in South Asians
did not differ appreciably from those in Europeans, except for 9p21.3 (per-allele odds ratio: 1.14 versus 1.27 respectively; P
for heterogeneity = 0.003). This large-scale gene-centric analysis has identified several novel genes for CAD that relate to
diverse biochemical and cellular functions and clarified the literature with regard to many previously suggested genes.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/428782
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simulazione ASN
Il report seguente simula gli indicatori relativi alla propria produzione scientifica in relazione alle soglie ASN 2021-2023 del proprio SC/SSD. Si ricorda che il superamento dei valori soglia (almeno 2 su 3) è requisito necessario ma non sufficiente al conseguimento dell'abilitazione. La simulazione si basa sui dati IRIS e sugli indicatori bibliometrici alla data indicata e non tiene conto di eventuali periodi di congedo obbligatorio, che in sede di domanda ASN danno diritto a incrementi percentuali dei valori. La simulazione può differire dall'esito di un’eventuale domanda ASN sia per errori di catalogazione e/o dati mancanti in IRIS, sia per la variabilità dei dati bibliometrici nel tempo. Si consideri che Anvur calcola i valori degli indicatori all'ultima data utile per la presentazione delle domande.
La presente simulazione è stata realizzata sulla base delle specifiche raccolte sul tavolo ER del Focus Group IRIS coordinato dall’Università di Modena e Reggio Emilia e delle regole riportate nel DM 589/2018 e allegata Tabella A. Cineca, l’Università di Modena e Reggio Emilia e il Focus Group IRIS non si assumono alcuna responsabilità in merito all’uso che il diretto interessato o terzi faranno della simulazione. Si specifica inoltre che la simulazione contiene calcoli effettuati con dati e algoritmi di pubblico dominio e deve quindi essere considerata come un mero ausilio al calcolo svolgibile manualmente o con strumenti equivalenti.