Omni 2.5m beadchip

Manufactured by Illumina

The Omni 2.5M BeadChip is a high-density genotyping microarray designed for whole-genome analysis. It features over 2.5 million genetic markers, providing comprehensive genomic coverage across the human genome.

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Lab products found in correlation

Human610 quad beadchip, by Illumina (3 mentions) Humanomniexpress beadchip, by Illumina (2 mentions) Hiseq 2000, by Illumina (1 mentions) Qiaamp dna blood mini kit, by Qiagen (1 mentions) Beadstudio 3, by Illumina (1 mentions) Genomestudio v2009, by Illumina (1 mentions) Omniexpress beadchip, by Illumina (1 mentions) Genomestudio v2011, by Illumina (1 mentions)

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BeadChips (68 citations) Omni 2.5M (14 citations) Omni 2.5M BeadChip array (3 citations) Illumina Omni 2.5M Exome Beadchip (2 citations)

7 protocols using omni 2.5m beadchip

Whole-Genome Sequencing and Genotyping in ADNI

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A total of 770 samples from ADNI1/GO/2 set were whole‐genome sequenced (WGS) and genotyped using the Illumina (San Diego, CA) Omni 2.5M BeadChip (42,732,452 variants). WGS calls were made using the Broad Institute best practices (BWA & GATK HaplotypeCaller).
Basic quality control checks were performed using standard procedure.25 Single nucleotide polymorphisms (SNPs) were excluded where genotype missingness was >0.02, Hardy–Weinberg equilibrium p value was <1e‐6, and SNP minor allele frequency was <0.01. This retained 7,808,548 SNPs for the analyses. Matching those SNPs with the latest publicly available GWAS AD summary statistics2 reduced that number to 5,771,686.

Leonenko G., Shoai M., Bellou E., Sims R., Williams J., Hardy J, & Escott‐Price V. (2019). Genetic risk for alzheimer disease is distinct from genetic risk for amyloid deposition. Annals of Neurology, 86(3), 427-435.

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ADNI Whole-Genome Sequencing Quality Control

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The whole-genome sequencing was performed on Illumina HiSeq2000 platform. The genome-wide SNPs were genotyped using the Illumina Omni 2.5M Bead Chip for the ADNI subjects.
Quality control was performed at both the individual level and SNP level. Subjects with a missing genotyping rate of >0.05, sex inconsistency, possible relative relationships, and European population outliers identified by multidimensional scaling (MDS) were excluded. The first four components of MDS analysis were used as covariates in subsequent analysis. SNPs with a missing call rate of >0.05, minor allele frequency <0.01, a significant deviation from Hardy-Weinberg equilibrium (P < 5 × 10^–6), and ambiguous strands were excluded. Finally, 9,845,494 SNPs from 386 subjects were included in the subsequent analyses.

Yang J., Wang Z., Fu Y., Xu J., Zhang Y., Qin W, & Zhang Q. (2022). Prediction value of the genetic risk of type 2 diabetes on the amnestic mild cognitive impairment conversion to Alzheimer’s disease. Frontiers in Aging Neuroscience, 14, 964463.

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Genetic Profiling in Asian and ADNI Cohorts

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Fasting peripheral venous blood (4–5 mL) was collected using anticoagulant tubes. The QIAamp DNA Blood Mini Kit (Qiagen, Hilden, Germany) was utilized to extract DNA from blood samples in the Han Chinese population. Participants' DNA was subjected to genotyping using Infinium Asian Screening Array. ADNI samples were genotyped with the Human 610‐Quad BeadChip, Illumina Human Omni Express BeadChip, and Illumina Omni 2.5 M BeadChip. One SNP in TREM1, rs2062323, was analyzed for this study. APOE and genome‐wide genotyping data were obtained from this database (adni.loni.usc.edu). The APOE genotypes were determined using rs429358 and rs7412.

Wang Z., Fu Y., Chen S., Huang Y., Ma Y., Wang Y., Tan L, & Yu J. (2023). Association of rs2062323 in the TREM1 gene with Alzheimer's disease and cerebrospinal fluid‐soluble TREM2. CNS Neuroscience & Therapeutics, 29(6), 1657-1666.

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Polygenic Hazard Score for Alzheimer's

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The ADNI samples were genotyped with the Omni 2.5 M BeadChip (Illumina, Inc, San Diego, CA) and basic QC was performed. APOE alleles were defined by rs7421 and re429358 which were genotyped by PCR amplification followed by HhaI restriction enzyme digestion and Metaphor Gel. We acquired a Polygenic Hazard Score (PHS) which was computed based on the combination of APOE and 31 other genetic variants from the ADNI database. Detailed information of the PHS can be found in a previous study [17 (link)]. In brief, International Genomics of Alzheimer's Project Stage 1 data with genotyped or imputed data was used to identified AD-associated SNPs. Then a PHS score for each participant was provided by a Cox proportional hazard model using genotype data from from Alzheimer's Disease Genetics Consortium phase 1 (excluding individuals from the ADNI).

Hou X.H., Suckling J., Shen X.N., Liu Y., Zuo C.T., Huang Y.Y., Li H.Q., Wang H.F., Tan C.C., Cui M., Dong Q., Tan L, & Yu J.T. (2023). Multipredictor risk models for predicting individual risk of Alzheimer’s disease. Journal of Translational Medicine, 21, 768.

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Genome-wide Genotyping in the ADNI Cohort

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Genome-wide genotyping was performed using the Illumina Human 610-Quad BeadChip (Illumina, Inc., San Diego, CA, USA) for ADNI-1 individuals by TGen (Phoenix, AZ, USA) and using the OmniExpress BeadChip for ADNI-GO/2 individuals by the Center for Applied Genomics of Children’s Hospital of Philadelphia (Philadelphia, PA, USA). Detailed genotyping protocols were described previously [8 ]. All assays were performed according to manufacturer protocols. Bead intensity data were used to call genotypes using BeadStudio 3.2 (Illumina) for the first release of ADNI-1 data, GenomeStudio v2009.1 (Illumina) for the second release of ADNI-1 data, and GenomeStudio v2011.1 (Illumina) for ADNI-GO/2. All genotype data was quality controlled, including checks for sex and identity, and the quality-controlled data were released on the ADNI LONI website (http://adni.loni.usc.edu) in Final Report and/or PLINK data formats. Of note, samples from the 818 individuals in the whole genome sequencing (WGS) sub-study described below (Section 2.2.5) underwent genome-wide genotyping using the Illumina Omni 2.5M BeadChip performed by Illumina. Thus, multiple genome-wide genotype array datasets are available for some ADNI participants. After QC, the Omni 2.5M genotype data in PLINK format were posted on the LONI website (http://adni.loni.usc.edu) in February 2014.

Saykin A.J., Shen L., Yao X., Kim S., Nho K., Risacher S.L., Ramanan V.K., Foroud T.M., Faber K.M., Sarwar N., Munsie L.M., Hu X., Soares H.D., Potkin S.G., Thompson P.M., Kauwe J.S., Kaddurah-Daouk R., Green R.C., Toga A.W, & Weiner M.W. (2015). Genetic Studies of Quantitative MCI and AD Phenotypes in ADNI: Progress, Opportunities, and Plans. Alzheimer's & dementia : the journal of the Alzheimer's Association, 11(7), 792-814.

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ADNI Genotyping and Quality Control

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The ADNI-1, ADNI-2, and ADNI-GO samples were genotyped with the Human 610-Quad BeadChip, Illumina Human Omni Express BeadChip and Ilumina Omni 2.5M BeadChip, respectively. PLINK software (version 1.07) was used in this step. The following criteria were utilized to perform a stringent QC assessment: call rates for individuals and SNPs were restricted to> 95%; minor allele frequencies (MAF) were restricted to > 0.05; p value for Hardy-Weinberg equilibrium test was restricted to > 0.001. An APOE genotyping kit was used to identify APOE alleles (polymorphisms rs7412 and rs429358) [36 (link)].

Wang Z.T., Chen S.D., Xu W., Chen K.L., Wang H.F., Tan C.C., Cui M., Dong Q., Tan L, & Yu J.T. (2019). Genome-wide association study identifies CD1A associated with rate of increase in plasma neurofilament light in non-demented elders. Aging (Albany NY), 11(13), 4521-4535.

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Identifying Deleterious Variants in ADNI

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Whole genome sequencing always derives millions of SNPs which can be partitioned into categories such as missense variants, synonymous variants, driver variants, passenger variants and so on. It means that not all of them are deleterious to gene function, let alone pathogenicity. The VEP tool can determine which genetic variants are deleterious with using SIFT scores [33] . Based on the sequence homology and physical properties of amino acids, SIFT evaluates the effect of each amino acid substitution on protein function.
In this study, we download the whole genome sequencing VCF files from the ADNI database (adni.loni. usc.edu) [34] , which contains 809 samples and each sample holds over 388 million SNPs by the Ilumina Omni 2.5 M BeadChip. To enhance the biological meanings and reduce the computational burden for downstream analysis, we use VEP to filter variants (IMPACT is HIGH or IMPACT is MODERATE and SIFT <0.05 and BIOTYPE is pro-tein_coding). After that, each sample approximately carries 1800 deleterious SNPs. Of note the SNPs contained in these samples are not exactly the same. Then, for each single sample, we encode gene corresponding to each deleterious SNP as '1' when IMPACT is MODERATE and as '2' when IMPACT is HIGH and the rest are '0'. Consequently, a matrix derived contains 809 samples and 16163 genes.

Zhou J., Qiu Y., Liu X., Xie Z., Lv S., Peng Y, & Li X. (2022). Annotating whole genome variants and constructing a multi-classifier based on samples of ADNI. Frontiers in bioscience (Landmark edition), 27(1).

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