title: Automated Assay of Telomere Length Measurement and Informatics for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort.
abstract: The Kaiser Permanente Research Program on Genes, Environment, and Health (RPGEH) Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort includes DNA specimens extracted from saliva samples of 110,266 individuals. Because of its relationship to aging, telomere length measurement was considered an important biomarker to develop on these subjects. To assay relative telomere length (TL) on this large cohort over a short time period, we created a novel high throughput robotic system for TL analysis and informatics. Samples were run in triplicate, along with control samples, in a randomized design. As part of quality control, we determined the within-sample variability and employed thresholds for the elimination of outlying measurements. Of 106,902 samples assayed, 105,539 (98.7%) passed all quality control (QC) measures. As expected, TL in general showed a decline with age and a sex difference. While telomeres showed a negative correlation with age up to 75 years, in those older than 75 years, age positively correlated with longer telomeres, indicative of an association of longer telomeres with more years of survival in those older than 75. Furthermore, while females in general had longer telomeres than males, this difference was significant only for those older than age 50. An additional novel finding was that the variance of TL between individuals increased with age. This study establishes reliable assay and analysis methodologies for measurement of TL in large, population-based human studies. The GERA cohort represents the largest currently available such resource, linked to comprehensive electronic health and genotype data for analysis.
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158-2517.
authors.forename: Kyle
authors.initials: K
authors.lastname: Lapham
authors.affiliation: Institute for Human Genetics, University of California, San Francisco, California 94143-0794 kvalem@humgen.ucsf.edu elizabeth.blackburn@ucsf.edu Cathy.Schaefer@kp.org RischN@humgen.ucsf.edu.
authors.forename: Mark N
authors.initials: MN
authors.lastname: Kvale
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158-2517.
authors.forename: Jue
authors.initials: J
authors.lastname: Lin
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, California 94612-2304.
authors.forename: Sheryl
authors.initials: S
authors.lastname: Connell
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, California 94612-2304.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Croen
authors.affiliation: Institute for Human Genetics, University of California, San Francisco, California 94143-0794.
authors.forename: Brad P
authors.initials: BP
authors.lastname: Dispensa
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158-2517.
authors.forename: Lynn
authors.initials: L
authors.lastname: Fang
authors.affiliation: Institute for Human Genetics, University of California, San Francisco, California 94143-0794.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hesselson
authors.affiliation: Institute for Human Genetics, University of California, San Francisco, California 94143-0794.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hoffmann
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, California 94612-2304.
authors.forename: Carlos
authors.initials: C
authors.lastname: Iribarren
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, California 94612-2304.
authors.forename: Eric
authors.initials: E
authors.lastname: Jorgenson
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, California 94612-2304.
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Kushi
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, California 94612-2304.
authors.forename: Dana
authors.initials: D
authors.lastname: Ludwig
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158-2517.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matsuguchi
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, California 94612-2304.
authors.forename: William B
authors.initials: WB
authors.lastname: McGuire
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, California 94612-2304.
authors.forename: Sunita
authors.initials: S
authors.lastname: Miles
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, California 94612-2304.
authors.forename: Charles P
authors.initials: CP
authors.lastname: Quesenberry
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, California 94612-2304.
authors.forename: Sarah
authors.initials: S
authors.lastname: Rowell
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, California 94612-2304.
authors.forename: Marianne
authors.initials: M
authors.lastname: Sadler
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, California 94612-2304.
authors.forename: Lori C
authors.initials: LC
authors.lastname: Sakoda
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, California 94612-2304.
authors.forename: David
authors.initials: D
authors.lastname: Smethurst
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, California 94612-2304.
authors.forename: Carol P
authors.initials: CP
authors.lastname: Somkin
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, California 94612-2304.
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Van Den Eeden
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, California 94612-2304.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Walter
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, California 94612-2304.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Whitmer
authors.affiliation: Institute for Human Genetics, University of California, San Francisco, California 94143-0794.
authors.forename: Pui-Yan
authors.initials: PY
authors.lastname: Kwok
authors.affiliation: Institute for Human Genetics, University of California, San Francisco, California 94143-0794 Division of Research, Kaiser Permanente Northern California, Oakland, California 94612-2304 Department of Epidemiology and Biostatistics, University of California, San Francisco, California 94158-2517 kvalem@humgen.ucsf.edu elizabeth.blackburn@ucsf.edu Cathy.Schaefer@kp.org RischN@humgen.ucsf.edu.
authors.forename: Neil
authors.initials: N
authors.lastname: Risch
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, California 94612-2304 kvalem@humgen.ucsf.edu elizabeth.blackburn@ucsf.edu Cathy.Schaefer@kp.org RischN@humgen.ucsf.edu.
authors.forename: Catherine
authors.initials: C
authors.lastname: Schaefer
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158-2517 kvalem@humgen.ucsf.edu elizabeth.blackburn@ucsf.edu Cathy.Schaefer@kp.org RischN@humgen.ucsf.edu.
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Blackburn
mesh_terms: D000328:Adult; D000375:Aging / Q000235:genetics*; D001331:Automation; D015331:Cohort Studies; D019295:Computational Biology / Q000379:methods*; D005260:Female; D005838:Genotype; D006262:Health; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D017720:Molecular Epidemiology; D012727:Sex Characteristics; D016615:Telomere / Q000235:genetics*
keywords: GERA cohort; quantitative PCR; relative telomere length; robotic assay; saliva DNA