A genome-wide screening and SNPs-to-genes approach to identify novel genetic risk factors associated with frontotemporal dementia

Ferrari, Raffaele; Grassi, Mario; Salvi, Erika; Borroni, Barbara; Palluzzi, Fernando; Pepe, Daniele; D’Avila, Francesca; Padovani, Alessandro; Archetti, Silvana; Rainero, Innocenzo; Rubino, Elisa; Pinessi, Lorenzo; Benussi, Luisa; Binetti, Giuliano; Ghidoni, Roberta; Galimberti, Daniela; Scarpini, Elio; Serpente, María; Rossi, Giacomina; Giaccone, Giorgio; Tagliavini, Fabrizio; Nacmias, Benedetta; Piaceri, Irene; Bagnoli, Silvia; Bruni, Amalia C.; Maletta, Raffaele; Bernardi, Livia; Postiglione, Alfredo; Milan, Graziella; Franceschi, M.; Puca, Annibale Alessandro; Novelli, Valeria; Barlassina, Cristina; Glorioso, Nicola; Manunta, Paolo; Singleton, Andrew B.; Cusi, Daniele; Hardy, John; Momeni, Parastoo

doi:10.1016/j.neurobiolaging.2015.06.005

Cited by 56 publications

(58 citation statements)

References 65 publications

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“…5d,e and Supplementary Fig. 18), it has been reported that top-ranking genes often include plausible candidates even if they are under the significance threshold 48,49 . On chromosome 6, some genes in the 9.22-9.61 Mb region, which included Hd1 itself, formed a higher peak than genes in the 7.81-8.38 Mb region (Fig.…”

Section: Misleading Association Owing To Allelic Heterogeneitymentioning

confidence: 93%

Genome-wide association study using whole-genome sequencing rapidly identifies new genes influencing agronomic traits in rice

et al. 2016

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A genome-wide association study (GWAS) can be a powerful tool for the identification of genes associated with agronomic traits in crop species, but it is often hindered by population structure and the large extent of linkage disequilibrium. In this study, we identified agronomically important genes in rice using GWAS based on whole-genome sequencing, followed by the screening of candidate genes based on the estimated effect of nucleotide polymorphisms. Using this approach, we identified four new genes associated with agronomic traits. Some genes were undetectable by standard SNP analysis, but we detected them using gene-based association analysis. This study provides fundamental insights relevant to the rapid identification of genes associated with agronomic traits using GWAS and will accelerate future efforts aimed at crop improvement.

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Section: Misleading Association Owing To Allelic Heterogeneitymentioning

confidence: 93%

Genome-wide association study using whole-genome sequencing rapidly identifies new genes influencing agronomic traits in rice

et al. 2016

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“…AAO was available for 411 out of 532 FTD patients that underwent Italian GWAS [3]. The mean AAO was 63.7 ± 20.7 (range, 36.0–82.0) with male/female ratio 187/224 (male 45.5%).…”

Section: Resultsmentioning

confidence: 99%

“…Our association analysis was carried out on 411 FTD patients, belonging to 7 Italian Centers (see Supplementary Table 1), already included in our previous study [3] and for whom AAO was available. Diagnosis of FTD, and FTD subtypes (i.e., behavioral variant FTD and primary progressive aphasia), was made according to current clinical criteria [12, 13].…”

Section: Methodsmentioning

confidence: 99%

“…Mutations in the Granulin (GRN) , C9orf72 , or Microtubule Associated Protein Tau (MAPT) , and, recently, the TANK binding kinase 1 ( TBK1 ) genes drive up to ∼40% of Mendelian cases [2]; for the remaining cases, multiple loci and genes appear to influence FTD risk with rather small effect size [3, 4]. …”

Section: Introductionmentioning

confidence: 99%

“…We recently carried out a genome-wide association study (GWAS) in FTD patients from Italy, and identified an extended number of genetic risk factors associated with disease in the Italian population [3]. …”

Section: Introductionmentioning

confidence: 99%

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Effects of Multiple Genetic Loci on Age at Onset in Frontotemporal Dementia

Ferrari¹,

Grassi

Graziano

et al. 2017

JAD

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In frontotemporal dementia (FTD), age at disease onset (AAO) is unpredictable in both early and late-onset cases; AAO variability is found even in autosomal dominant FTD. The present study was aimed at identifying genetic modifiers modulating AAO in a large cohort of Italian FTD patients. We conducted an association analysis on 411 FTD patients, belonging to 7 Italian Centers, and for whom AAO was available. Population structure was evaluated by principal component analysis to infer continuous axes of genetic variation, and single linear regression models were applied. A genetic score (GS) was calculated on the basis of suggestive single nucleotide polymorphisms (SNPs) found by association analyses. GS showed genome-wide significant slope decrease by −3.86 (95%CI: −4.64 to −3.07, p < 2 × 10−16) per standard deviation of the GS for 6 SNPs mapping to genes involved in neuronal development and signaling, axonal myelinization, and glutamatergic/GABA neurotransmission. An increase of the GS was associated with a decrease of the AAO. Our data indicate that there is indeed a genetic component that underpins and modulates up to 14.5% of variability of AAO in Italian FTD. Future studies on genetic modifiers in FTD are warranted.

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APOEgene and neuropsychiatric disorders and endophenotypes: A comprehensive review

Forero

López-Léon

González-Giraldo

et al. 2016

American J of Med Genetics Pt B

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The Apolipoprotein E (APOE) gene is one of the main candidates in neuropsychiatric genetics, with hundreds of studies carried out in order to explore the possible role of polymorphisms in the APOE gene in a large number of neurological diseases, psychiatric disorders, and related endophenotypes. In the current article, we provide a comprehensive review of the structural and functional aspects of the APOE gene and its relationship with brain disorders. Evidence from genome-wide association studies and meta-analyses shows that the APOE gene has been significantly associated with several neurodegenerative disorders. Cellular and animal models show growing evidence of the key role of APOE in mechanisms of brain plasticity and behavior. Future analyses of the APOE gene might find a possible role in other neurological diseases and psychiatric disorders and related endophenotypes. © 2016 Wiley Periodicals, Inc.

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A genome-wide screening and SNPs-to-genes approach to identify novel genetic risk factors associated with frontotemporal dementia

Cited by 56 publications

References 65 publications

Genome-wide association study using whole-genome sequencing rapidly identifies new genes influencing agronomic traits in rice

Genome-wide association study using whole-genome sequencing rapidly identifies new genes influencing agronomic traits in rice

Effects of Multiple Genetic Loci on Age at Onset in Frontotemporal Dementia

APOEgene and neuropsychiatric disorders and endophenotypes: A comprehensive review

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