Nature Communications (Jan 2024)
Human whole-exome genotype data for Alzheimer’s disease
- 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. Kuzma,
- Wan-Ping Lee,
- Laura Cantwell,
- Heather Nicaretta,
- Alzheimer’s Disease Sequencing Project,
- Jonathan Haines,
- Lindsay Farrer,
- Sudha Seshadri,
- Zoran Brkanac,
- Carlos Cruchaga,
- Margaret Pericak-Vance,
- Richard P. Mayeux,
- William S. Bush,
- Anita Destefano,
- Eden Martin,
- Gerard D. Schellenberg,
- Li-San Wang
Affiliations
- Yuk Yee Leung
- Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Adam C. Naj
- Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Yi-Fan Chou
- Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Otto Valladares
- Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Michael Schmidt
- Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami
- Kara Hamilton-Nelson
- Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami
- Nicholas Wheeler
- Department of Population and Quantitative Health Sciences, Case Western Reserve University
- Honghuang Lin
- Department of Medicine, UMass Chan Medical School
- Prabhakaran Gangadharan
- Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Liming Qu
- Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Kaylyn Clark
- Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Amanda B. Kuzma
- Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Wan-Ping Lee
- Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Laura Cantwell
- Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Heather Nicaretta
- Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Alzheimer’s Disease Sequencing Project
- Jonathan Haines
- Department of Population and Quantitative Health Sciences, Case Western Reserve University
- Lindsay Farrer
- Department of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine
- Sudha Seshadri
- Boston University School of Medicine
- Zoran Brkanac
- Department of Psychiatry and Behavioral Sciences, University of Washington
- Carlos Cruchaga
- Washington University School of Medicine
- Margaret Pericak-Vance
- Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami
- Richard P. Mayeux
- Department of Neurology, Taub Institute for Research on Alzheimer’s Disease and the Aging Brain and the Gertrude H. Sergievsky Center, Columbia University and the New York Presbyterian Hospital
- William S. Bush
- Department of Population and Quantitative Health Sciences, Case Western Reserve University
- Anita Destefano
- Department of Biostatistics, Boston University School of Public Health
- Eden Martin
- Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami
- Gerard D. Schellenberg
- Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Li-San Wang
- Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- DOI
- https://doi.org/10.1038/s41467-024-44781-7
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 15
Abstract
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.
