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Human660w quad v1 a

Manufactured by Illumina

The Human660W-Quad_v1_A is a high-density genotyping array designed by Illumina. It is capable of interrogating over 660,000 genetic variants across the human genome. The array employs Illumina's BeadChip technology to provide researchers with a comprehensive and efficient platform for genetic analysis.

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10 protocols using human660w quad v1 a

1

Genome-wide SNP Genotyping and Quality Control

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Genome-wide SNP genotyping was performed using the Illumina Human 660 W-Quad_v1_A, (Illumina, San Diego, CA) (n=560,768 SNPs). According to the data set release as well as the quality control and quality assurance policies of the GENEVA consortium(36 (link)), genotypes were not reported for any SNP which had a call rate less than 85% or which had more than 1 replicate error as defined with the HapMap control samples. Identical-by-descent (IBD) coefficients were estimated using 107,014 au-tosomal SNPs with missing call rate < 5% and no closer than 15 kb apart(36 (link)).
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2

Genotype Imputation for Cohort Comparison

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To allow for direct comparisons with results from the phs000517 cohort, we used imputed SNPs from the phs000799 cohort, which was genotyped using the Affymetrix 6.0 platform, to match the SNPs measured on the Human660W-Quad_v1_A and Illumina Human 1M platforms, which were used to genotype the phs000517 cohort. We ran our BridGE approach on both the non-imputed dataset and imputed dataset and reported discoveries for both. These imputed and non-imputed versions of the phs000799 dataset are referred to as “CHN799 imputed” and “CHN799 non-imputed”.
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3

Genome-wide SNP Genotyping and Quality Control

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Genome-wide SNP genotyping was performed using the Illumina Human 660 W-Quad_v1_A, (Illumina, San Diego, CA) (n=560,768 SNPs). According to the data set release as well as the quality control and quality assurance policies of the GENEVA consortium(36 (link)), genotypes were not reported for any SNP which had a call rate less than 85% or which had more than 1 replicate error as defined with the HapMap control samples. Identical-by-descent (IBD) coefficients were estimated using 107,014 au-tosomal SNPs with missing call rate < 5% and no closer than 15 kb apart(36 (link)).
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4

Cataract and HDL GWAS in PMRP

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The Marshfield sample was selected from the publicly available data in A Genome-Wide Association Study on Cataract and HDL in the Personalized Medicine Research Project Cohort -Study Accession: phs000170.v1.p1 (dbGaP). Details about the participants were described elsewhere (McCarty et al., 2005 (McCarty et al., , 2008)) . Cases were defined as any diagnosed cancer excluding minor skin cancer and AAO of cancer was defined by the date of the earliest cancer diagnosis in the registry. Covariates included in this study were age, gender, alcohol use in the past month (yes or no), obesity status, and smoking status (never smoking, current smoking and past smoking). Obesity was defind as a body mass index (BMI) ≥ 30 kg/m 2 . Genotyping data using the ILLUMINA Human660W-Quad_v1_A were available for 3894 individuals. The genotypes of 23 SNPs within the HNF1B gene were available in this data.
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5

Cataract and HDL GWAS in PMRP

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The Marshfield sample was selected from the publicly available data in A Genome-Wide Association Study on Cataract and HDL in the Personalized Medicine Research Project Cohort -Study Accession: phs000170.v1.p1 (dbGaP). Details about the participants were described elsewhere (McCarty et al., 2005 (McCarty et al., , 2008)) . Cases were defined as any diagnosed cancer excluding minor skin cancer and AAO of cancer was defined by the date of the earliest cancer diagnosis in the registry. Covariates included in this study were age, gender, alcohol use in the past month (yes or no), obesity status, and smoking status (never smoking, current smoking and past smoking). Obesity was defind as a body mass index (BMI) ≥ 30 kg/m 2 . Genotyping data using the ILLUMINA Human660W-Quad_v1_A were available for 3894 individuals. The genotypes of 23 SNPs within the HNF1B gene were available in this data.
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6

Genotyping and Imputation of Genomic Data

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SNP genotype data were acquired on the Illumina Human660W-Quadv1_A (eMERGE), Illumina HumanOmni1-Quad (VESPA), HumanOmni5-Quad (VESPA) and Affymetrix 6.0 SNP array (ARIC) platforms. Quality control (QC) steps for the EHR data sets were performed per the published protocols established by the eMERGE Genomics Working Group.23 (link) For imputation, palindromic alleles were aligned to the positive strand using allele frequency information from the 1000 Genomes Project. SNPs were pre-phased using SHAPEIT,24 (link) and data were imputed using IMPUTE225 (link) and the 10/2014 release of the 1000 Genomes cosmopolitan reference haplotypes. QC for the ARIC data set followed the guidelines accompanying the dbGaP release including removing SNPs with chromosomal anomalies and with >5 discordant calls in replicate samples, and using a predefined subset of unrelated subjects. QC analyses used PLINK v1.07.26 (link) After filtering for a sample missingness rate<2.0%, a SNP missingness rate<2.0% and a SNP deviation from Hardy-Weinberg<0.001, there were 627,580 SNPs with MAF>1.0%. The merged intersection of the ARIC and imputed EHR data sets contained 488,525 SNPs with MAF>1.0%.
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7

Genetic Data Harmonization for Analyses

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ARIC: Genotype data were acquired on the Affymetrix 6.0 SNP array. Quality control steps for the ARIC data set followed the guidelines accompanying the dbGaP release and included removing SNPs with pre-identified chromosomal anomalies and with >5 discordant calls in replicate samples, and used a subset of unrelated subjects identified by the ARIC study. eMERGE: SNP genotype data were acquired on the Illumina Human660W-Quadv1_A. BioVU AF data set: Subjects were genotyped on the Illumina 610-quad Beadchip.14 (link)BioVU VESPA: Subjects were genotyped on the Illumina HumanOmni1-Quad and HumanOmni5-Quad platforms. Quality control steps for the eMERGE and BioVU data sets used established protocols18 (link) including filtering for a sample missingness rate<2.0%, a SNP missingness rate<2.0% and a SNP deviation from Hardy-Weinberg<0.001
All data sets were imputed to the October 2014 release of the 1000 Genomes cosmopolitan reference haplotypes. SNPs were pre-phased using SHAPEIT19 (link) and imputed using IMPUTE2.20 (link). The genetic correlation analyses used an intersection of the unimputed ARIC and imputed eMERGE data set and contained 503,404 SNPs with MAF>1.0%. The BSLMM analyses used an LD-reduced (r-square=0.9) set of SNPs with MAF>1.0% present on all platforms (n= 645,714 SNPs).
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8

Genome-wide Genotyping and Imputation

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All men from the KP cohort were genotyped for over 650,000 SNPs on four race or ethnicity-specific Affymetrix Axiom arrays optimized for individuals of non-Hispanic white, Latino, East Asian, and African-American race or ethnicity respectively75 (link)76 (link). Genotype quality control (QC) procedures and imputation for the original GERA cohort assays were performed on an array-wise basis, as has been described previously26 (link)75 (link)77 (link). Briefly, imputation was done by pre-phasing KP genotypes with SHAPEIT v2.5 (ref. 78 ), and then imputing variants from the 1000 Genomes Project October 2014 release with 2,504 samples (http://1000genomes.org) as a cosmopolitan reference panel with IMPUTE2 v2.3.1 (ref. 79 (link)). Our discovery GWAS analysis in the non-Hispanic white non-cases ultimately assessed 10,109,774 variants with r2info≥0.3 and MAF≥0.01.
Genotyping, imputation and QC were similar in the three non-KP replication cohorts as has been previously described. Briefly, PEGASUS men were genotyped with the Illumina HumanOmni2.5 Beadchip34 (link); Malmö men were genotyped on the Illumina Human OmniExpressExome v1.0 BeadChip; and BioVU men were genotyped on the Illumina Human660W-Quadv1_A, HumanOmin1-Quad, and HumanOmni5-Quad73 (link). All studies were pre-phased and imputed with the same software as the GERA cohort, except Malmö used SHAPEIT v2r790 and IMPUTE2 v2.3.0.
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9

SNP Genotyping and Imputation for EHR Data

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SNP genotype data for the EHR populations were acquired on the Illumina Human660W-Quadv1_A, HumanOmni1-Quad, HumanOmni5-Quad, MEGA-EX, Human610, Human550, HumanOmniExpressExome-8v1.2A and MegArray platforms. Quality control (QC) steps for the EHR data sets were performed per previously published protocols.12 (link) QC analyses used PLINK v 1.90β3.13 (link) SNPs were pre-phased using SHAPEIT,14 (link) imputed using IMPUTE215 (link) in conjunction with the 10/2014 release of the 1000 Genomes cosmopolitan reference haplotypes. Imputed data were filtered for a sample missingness rate<2%, a SNP missingness rate<4% and a SNP deviation from Hardy-Weinberg<10−6. Principal components were generated using the SNPRelate package.16 (link)
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10

Genotyping Quality Control in eMERGE

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Genotyping was performed using the Illumina Human660W-Quadv1_A and the Illumina1M BeadChips for European Americans and African Americans, respectively, as previously described [22] (link). Of the SNPs on each array, 474,366 SNPs and 905,285 SNPs, respectively, passed quality control filters for tests of genotyping efficiency (>99% call rate), and minor allele frequency (>5%). Details of eMERGE quality control have been previously published [23] ,[24] (link). eMERGE Network data have been deposited into the Database for Genotypes and Phenotypes (dbGaP).
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