NeuroChip, an updated version of the NeuroX genotyping platform to rapidly screen for variants associated with neurological diseases

Blauwendraat, Cornelis; Faghri, Faraz; Pihlstrøm, Lasse; Geiger, Joshua T.; Elbaz, Alexis; Lesage, Suzanne; Corvol, Jean‐Christophe; May, Patrick; Nicolas, Aude; Abramzon, Yevgeniya; Murphy, Natalie A.; Gibbs, J. Raphael; Ryten, Mina; Ferrari, Raffaele; Brás, José; Guerreiro, Rita; Williams, Julie; Sims, Rebecca; Lubbe, Steven; Hernandez, Dena G.; Mok, Kin Y.; Robak, Laurie; Campbell, Roy H.; Rogaeva, Ekaterina; Traynor, Bryan J.; Chia, Ruth; Chung, Sun Ju; Hardy, John; Brice, Alexis; Wood, Nicholas W.; Houlden, Henry; Liu, Zhandong; Morris, Huw R.; Gasser, Thomas; Krüger, Rejko; Heutink, Peter; Sharma, Manu; Simón‐Sánchez, Javier; Nalls, Mike A.; Singleton, Andrew B.; Scholz, Sonja W.

doi:10.1016/j.neurobiolaging.2017.05.009

Cited by 119 publications

(122 citation statements)

References 22 publications

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“…Genetic variants in APOE (rs429358 determining the E4 carrier status), MAPT (rs1052587 tagging the H1/H2haplotype), and SNCA (rs356220 as risk variant for PD) have been assessed using the NeuroChip, the second generation of the the NeuroX array …”

Section: Methodssupporting

confidence: 89%

Dementia with lewy bodies: GBA1 mutations are associated with cerebrospinal fluid alpha‐synuclein profile

et al. 2019

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Background Patients with dementia with Lewy bodies reveal a variable pathology including alpha‐synuclein, amyloid‐beta, and Tau. Mutations in GBA1 are specifically associated with synucleinopathies. PD patients with GBA1 mutations show reduced CSF levels of total alpha‐synuclein. Objective Whether GBA1 mutations are associated with a CSF alpha‐synuclein profile in dementia with Lewy bodies. Methods Screening of the GBA1 gene and single‐nucleotide polymorphisms in SNCA rs356220, APOE rs429358, and MAPT rs1052587 as well as CSF levels of total alpha‐synuclein, amyloid‐beta1‐42, total‐Tau, phospho‐Tau, and neurofilament light chain were assessed in 100 dementia with Lewy bodies and 39 controls cross‐sectionally. Results Severity of GBA1 mutations was associated with a younger age at onset and higher prevalence of rapid eye movement sleep behavior disorder. CSF levels of total alpha‐synuclein were lowest in DLBGBA_pathogenic compared to DLBGBA_mild and DLBGBA_wildtype. Conclusion Similar to PD, pathogenic GBA1 mutations seem to be associated with CSF alpha‐synuclein profiles in dementia with Lewy bodies. That might be useful for patient stratification for specific alpha‐synuclein–lowering compounds. © 2019 International Parkinson and Movement Disorder Society

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Section: Methodssupporting

confidence: 89%

Dementia with lewy bodies: GBA1 mutations are associated with cerebrospinal fluid alpha‐synuclein profile

et al. 2019

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“…Several of the loci identified more recently were not present on the first iteration of the NeuroX array. Increased coverage, such as that available from the latest version of the NeuroX chip version 2 (Blauwendraat et al, 2017), could provide additional information for generating more accurate risk scores thereby providing a better predictive model.…”

Section: Discussionmentioning

confidence: 99%

Polygenic risk score in postmortem diagnosed sporadic early-onset Alzheimer's disease

Chaudhury

Patel

Barber

et al. 2018

Neurobiology of Aging

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Sporadic early-onset Alzheimer’s disease (sEOAD) exhibits the symptoms of late-onset Alzheimer’s disease but lacks the familial aspect of the early-onset familial form. The genetics of Alzheimer’s disease (AD) identifies APOE ε4 to be the greatest risk factor; however, it is a complex disease involving both environmental risk factors and multiple genetic loci. Polygenic risk scores (PRSs) accumulate the total risk of a phenotype in an individual based on variants present in their genome. We determined whether sEOAD cases had a higher PRS compared to controls. A cohort of sEOAD cases was genotyped on the NeuroX array, and PRSs were generated using PRSice. The target data set consisted of 408 sEOAD cases and 436 controls. The base data set was collated by the International Genomics of Alzheimer’s Project consortium, with association data from 17,008 late-onset Alzheimer’s disease cases and 37,154 controls, which can be used for identifying sEOAD cases due to having shared phenotype. PRSs were generated using all common single nucleotide polymorphisms between the base and target data set, PRS were also generated using only single nucleotide polymorphisms within a 500 kb region surrounding the APOE gene. Sex and number of APOE ε2 or ε4 alleles were used as variables for logistic regression and combined with PRS. The results show that PRS is higher on average in sEOAD cases than controls, although there is still overlap among the whole cohort. Predictive ability of identifying cases and controls using PRSice was calculated with 72.9% accuracy, greater than the APOE locus alone (65.2%). Predictive ability was further improved with logistic regression, identifying cases and controls with 75.5% accuracy.

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“…Recently, the NeuroX array, a genotyping platform, has been generated to aid in the diagnosis of neurodegenerative disorders, including ALS (Nails et al., ). An improved version of NeuroX, the NeuroChip that allows for high‐throughput screening of variants and loci implicated in neurodegeneration, including ALS, has also become available (Blauwendraat et al., ).…”

Section: Introductionmentioning

confidence: 99%

New molecular diagnostic trends and biomarkers for amyotrophic lateral sclerosis

et al. 2019

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Amyotrophic lateral sclerosis (ALS) is a rare and fatal neurodegenerative disorder. Two forms are recognized, familial (FALS) that accounts for 5–10% of ALS cases, and sporadic (SALS) that accounts for the rest. Early diagnosis of ALS is important because it improves their therapeutic efficacy. Current diagnosis is based on clinical assessment and requires approximately 12 months, leading to a significant delay in drug administration. Therefore, new methods are required for the earlier diagnosis of ALS. Screening for pathogenic variants in known ALS‐associated genes is already exploited as a diagnostic tool in ALS but cannot be applied for population‐based screening. New circulating biomarkers (proteins or small molecules) are needed for initial screening, whereas specific diagnostic methods can be applied to confirm the presence of pathogenic variants in the selected population subgroup. Lipids appear as promising biomarkers for population‐based screening and for monitoring disease progression. Genetic analysis can also assist in the prediction of disease progression by analyzing disease‐modifying genes, for example, EPHA4 and CHGB. Furthermore, molecular diagnosis will aid the stratification of ALS patients for improved pharmacological approaches. Here, we discuss current and novel diagnostic strategies and how they can be applied to revolutionize the field of ALS molecular diagnosis.

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NeuroChip, an updated version of the NeuroX genotyping platform to rapidly screen for variants associated with neurological diseases

Cited by 119 publications

References 22 publications

Dementia with lewy bodies: GBA1 mutations are associated with cerebrospinal fluid alpha‐synuclein profile

Dementia with lewy bodies: GBA1 mutations are associated with cerebrospinal fluid alpha‐synuclein profile

Polygenic risk score in postmortem diagnosed sporadic early-onset Alzheimer's disease

New molecular diagnostic trends and biomarkers for amyotrophic lateral sclerosis

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