title: Genotyping Informatics and Quality Control for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort.
abstract: The Kaiser Permanente (KP) Research Program on Genes, Environment and Health (RPGEH), in collaboration with the University of California-San Francisco, undertook genome-wide genotyping of >100,000 subjects that constitute the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. The project, which generated >70 billion genotypes, represents the first large-scale use of the Affymetrix Axiom Genotyping Solution. Because genotyping took place over a short 14-month period, creating a near-real-time analysis pipeline for experimental assay quality control and final optimized analyses was critical. Because of the multi-ethnic nature of the cohort, four different ethnic-specific arrays were employed to enhance genome-wide coverage. All assays were performed on DNA extracted from saliva samples. To improve sample call rates and significantly increase genotype concordance, we partitioned the cohort into disjoint packages of plates with similar assay contexts. Using strict QC criteria, the overall genotyping success rate was 103,067 of 109,837 samples assayed (93.8%), with a range of 92.1-95.4% for the four different arrays. Similarly, the SNP genotyping success rate ranged from 98.1 to 99.4% across the four arrays, the variation depending mostly on how many SNPs were included as single copy vs. double copy on a particular array. The high quality and large scale of genotype data created on this cohort, in conjunction with comprehensive longitudinal data from the KP electronic health records of participants, will enable a broad range of highly powered genome-wide association studies on a diversity of traits and conditions.
authors.affiliation: Institute for Human Genetics, University of California, San Francisco, California 94143 kvalem@humgen.ucsf.edu Cathy.Schaefer@kp.org pui.kwok@ucsf.edu rischn@humgen.ucsf.edu.
authors.forename: Mark N
authors.initials: MN
authors.lastname: Kvale
authors.affiliation: Institute for Human Genetics, University of California, San Francisco, California 94143.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hesselson
authors.affiliation: Institute for Human Genetics, University of California, San Francisco, California 94143 Department of Epidemiology and Biostatistics, University of California, San Francisco, California 94158.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hoffmann
authors.affiliation: Institute for Human Genetics, University of California, San Francisco, California 94143.
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Affymetrix Inc., Santa Clara, California 95051.
authors.forename: David
authors.initials: D
authors.lastname: Chan
authors.affiliation: Kaiser Permanente Northern California Division of Research, Oakland, California 94612.
authors.forename: Sheryl
authors.initials: S
authors.lastname: Connell
authors.affiliation: Kaiser Permanente Northern California Division of Research, Oakland, California 94612.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Croen
authors.affiliation: Institute for Human Genetics, University of California, San Francisco, California 94143.
authors.forename: Brad P
authors.initials: BP
authors.lastname: Dispensa
authors.affiliation: Institute for Human Genetics, University of California, San Francisco, California 94143.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Eshragh
authors.affiliation: Affymetrix Inc., Santa Clara, California 95051.
authors.forename: Andrea
authors.initials: A
authors.lastname: Finn
authors.affiliation: Affymetrix Inc., Santa Clara, California 95051.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Gollub
authors.affiliation: Kaiser Permanente Northern California Division of Research, Oakland, California 94612.
authors.forename: Carlos
authors.initials: C
authors.lastname: Iribarren
authors.affiliation: Kaiser Permanente Northern California Division of Research, Oakland, California 94612.
authors.forename: Eric
authors.initials: E
authors.lastname: Jorgenson
authors.affiliation: Kaiser Permanente Northern California Division of Research, Oakland, California 94612.
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Kushi
authors.affiliation: Institute for Human Genetics, University of California, San Francisco, California 94143.
authors.forename: Richard
authors.initials: R
authors.lastname: Lao
authors.affiliation: Affymetrix Inc., Santa Clara, California 95051.
authors.forename: Yontao
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Kaiser Permanente Northern California Division of Research, Oakland, California 94612.
authors.forename: Dana
authors.initials: D
authors.lastname: Ludwig
authors.affiliation: Institute for Human Genetics, University of California, San Francisco, California 94143.
authors.forename: Gurpreet K
authors.initials: GK
authors.lastname: Mathauda
authors.affiliation: Kaiser Permanente Northern California Division of Research, Oakland, California 94612.
authors.forename: William B
authors.initials: WB
authors.lastname: McGuire
authors.affiliation: Affymetrix Inc., Santa Clara, California 95051.
authors.forename: Gangwu
authors.initials: G
authors.lastname: Mei
authors.affiliation: Kaiser Permanente Northern California Division of Research, Oakland, California 94612.
authors.forename: Sunita
authors.initials: S
authors.lastname: Miles
authors.affiliation: Affymetrix Inc., Santa Clara, California 95051.
authors.forename: Michael
authors.initials: M
authors.lastname: Mittman
authors.affiliation: Affymetrix Inc., Santa Clara, California 95051.
authors.forename: Mohini
authors.initials: M
authors.lastname: Patil
authors.affiliation: Kaiser Permanente Northern California Division of Research, Oakland, California 94612.
authors.forename: Charles P
authors.initials: CP
authors.lastname: Quesenberry
authors.affiliation: Kaiser Permanente Northern California Division of Research, Oakland, California 94612.
authors.forename: Dilrini
authors.initials: D
authors.lastname: Ranatunga
authors.affiliation: Kaiser Permanente Northern California Division of Research, Oakland, California 94612.
authors.forename: Sarah
authors.initials: S
authors.lastname: Rowell
authors.affiliation: Kaiser Permanente Northern California Division of Research, Oakland, California 94612.
authors.forename: Marianne
authors.initials: M
authors.lastname: Sadler
authors.affiliation: Kaiser Permanente Northern California Division of Research, Oakland, California 94612.
authors.forename: Lori C
authors.initials: LC
authors.lastname: Sakoda
authors.affiliation: Affymetrix Inc., Santa Clara, California 95051.
authors.forename: Michael
authors.initials: M
authors.lastname: Shapero
authors.affiliation: Kaiser Permanente Northern California Division of Research, Oakland, California 94612.
authors.forename: Ling
authors.initials: L
authors.lastname: Shen
authors.affiliation: Institute for Human Genetics, University of California, San Francisco, California 94143.
authors.forename: Tanu
authors.initials: T
authors.lastname: Shenoy
authors.affiliation: Kaiser Permanente Northern California Division of Research, Oakland, California 94612.
authors.forename: David
authors.initials: D
authors.lastname: Smethurst
authors.affiliation: Kaiser Permanente Northern California Division of Research, Oakland, California 94612.
authors.forename: Carol P
authors.initials: CP
authors.lastname: Somkin
authors.affiliation: Kaiser Permanente Northern California Division of Research, Oakland, California 94612.
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Van Den Eeden
authors.affiliation: Kaiser Permanente Northern California Division of Research, Oakland, California 94612.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Walter
authors.affiliation: Institute for Human Genetics, University of California, San Francisco, California 94143.
authors.forename: Eunice
authors.initials: E
authors.lastname: Wan
authors.affiliation: Affymetrix Inc., Santa Clara, California 95051.
authors.forename: Teresa
authors.initials: T
authors.lastname: Webster
authors.affiliation: Kaiser Permanente Northern California Division of Research, Oakland, California 94612.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Whitmer
authors.affiliation: Institute for Human Genetics, University of California, San Francisco, California 94143.
authors.forename: Simon
authors.initials: S
authors.lastname: Wong
authors.affiliation: Kaiser Permanente Northern California Division of Research, Oakland, California 94612.
authors.forename: Chia
authors.initials: C
authors.lastname: Zau
authors.affiliation: Affymetrix Inc., Santa Clara, California 95051.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: Kaiser Permanente Northern California Division of Research, Oakland, California 94612 kvalem@humgen.ucsf.edu Cathy.Schaefer@kp.org pui.kwok@ucsf.edu rischn@humgen.ucsf.edu.
authors.forename: Catherine
authors.initials: C
authors.lastname: Schaefer
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco, California 94158 kvalem@humgen.ucsf.edu Cathy.Schaefer@kp.org pui.kwok@ucsf.edu rischn@humgen.ucsf.edu.
authors.forename: Pui-Yan
authors.initials: PY
authors.lastname: Kwok
authors.affiliation: Institute for Human Genetics, University of California, San Francisco, California 94143 Department of Epidemiology and Biostatistics, University of California, San Francisco, California 94158 Kaiser Permanente Northern California Division of Research, Oakland, California 94612 kvalem@humgen.ucsf.edu Cathy.Schaefer@kp.org pui.kwok@ucsf.edu rischn@humgen.ucsf.edu.
authors.forename: Neil
authors.initials: N
authors.lastname: Risch
mesh_terms: D000328:Adult; D000375:Aging / Q000235:genetics*; D015331:Cohort Studies; D019295:Computational Biology / Q000379:methods*; D005260:Female; D060005:Genotyping Techniques / Q000379:methods*; D006262:Health; D006801:Humans; D008297:Male; D017720:Molecular Epidemiology; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D011786:Quality Control
keywords: Affymetrix Axiom; GERA cohort; genome-wide genotyping; quality control; saliva DNA