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Human whole-exome genotype data for Alzheimer’s disease

Author

Listed:
  • Yuk Yee Leung

    (University of Pennsylvania)

  • Adam C. Naj

    (University of Pennsylvania
    University of Pennsylvania)

  • Yi-Fan Chou

    (University of Pennsylvania)

  • Otto Valladares

    (University of Pennsylvania)

  • Michael Schmidt

    (Miller School of Medicine, University of Miami
    University of Miami)

  • Kara Hamilton-Nelson

    (Miller School of Medicine, University of Miami
    University of Miami)

  • Nicholas Wheeler

    (Case Western Reserve University
    Case Western Reserve University)

  • Honghuang Lin

    (UMass Chan Medical School)

  • Prabhakaran Gangadharan

    (University of Pennsylvania)

  • Liming Qu

    (University of Pennsylvania)

  • Kaylyn Clark

    (University of Pennsylvania)

  • Amanda B. Kuzma

    (University of Pennsylvania)

  • Wan-Ping Lee

    (University of Pennsylvania)

  • Laura Cantwell

    (University of Pennsylvania)

  • Heather Nicaretta

    (University of Pennsylvania)

  • Jonathan Haines

    (Case Western Reserve University
    Case Western Reserve University)

  • Lindsay Farrer

    (Boston University Chobanian & Avedisian School of Medicine
    Boston University School of Public Health)

  • Sudha Seshadri

    (Boston University School of Medicine
    University of Texas Health Sciences Center)

  • Zoran Brkanac

    (University of Washington)

  • Carlos Cruchaga

    (Washington University School of Medicine)

  • Margaret Pericak-Vance

    (Miller School of Medicine, University of Miami
    University of Miami)

  • Richard P. Mayeux

    (Columbia University and the New York Presbyterian Hospital)

  • William S. Bush

    (Case Western Reserve University
    Case Western Reserve University)

  • Anita Destefano

    (Boston University School of Public Health
    Boston University School of Medicine)

  • Eden Martin

    (Miller School of Medicine, University of Miami
    University of Miami)

  • Gerard D. Schellenberg

    (University of Pennsylvania)

  • Li-San Wang

    (University of Pennsylvania)

Abstract

The heterogeneity of the whole-exome sequencing (WES) data generation methods present a challenge to a joint analysis. Here we present a bioinformatics strategy for joint-calling 20,504 WES samples collected across nine studies and sequenced using ten capture kits in fourteen sequencing centers in the Alzheimer’s Disease Sequencing Project. The joint-genotype called variant-called format (VCF) file contains only positions within the union of capture kits. The VCF was then processed specifically to account for the batch effects arising from the use of different capture kits from different studies. We identified 8.2 million autosomal variants. 96.82% of the variants are high-quality, and are located in 28,579 Ensembl transcripts. 41% of the variants are intronic and 1.8% of the variants are with CADD > 30, indicating they are of high predicted pathogenicity. Here we show our new strategy can generate high-quality data from processing these diversely generated WES samples. The improved ability to combine data sequenced in different batches benefits the whole genomics research community.

Suggested Citation

  • Yuk Yee Leung & Adam C. Naj & Yi-Fan Chou & Otto Valladares & Michael Schmidt & Kara Hamilton-Nelson & Nicholas Wheeler & Honghuang Lin & Prabhakaran Gangadharan & Liming Qu & Kaylyn Clark & Amanda B., 2024. "Human whole-exome genotype data for Alzheimer’s disease," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-44781-7
    DOI: 10.1038/s41467-024-44781-7
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    References listed on IDEAS

    as
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