Evidence map›Paper›PMID 29857119›Full record

ArticleGenomics2019

Quality control and integration of genotypes from two calling pipelines for whole genome sequence data in the Alzheimer's disease sequencing project.

Adam C Naj, Honghuang Lin, Badri N Vardarajan, Simon White, Daniel Lancour, Yiyi Ma, Michael Schmidt, Fangui Sun, Mariusz Butkiewicz, William S Bush and 26 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genomics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

45 citing papers in PubMed.

  1. Article
  2. Article
  3. Stratification by a polygenic risk score of common variation aids in Alzheimer's disease rare variant discovery.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Observational
  4. Article
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  14. The role of genomic-informed risk assessments in predicting dementia outcomes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  15. Integrative multi-omics approaches identify molecular pathways and improve Alzheimer's disease risk prediction.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  16. Article
  17. The Role of Genomic-Informed Risk Assessments in Predicting Dementia Outcomes.medRxiv : the preprint server for health sciences · 2025
    Article
  18. Article
  19. Article
  20. Alzheimer's Disease Sequencing Project release 4 whole genome sequencing dataset.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

36 authors.

Adam C NajDepartment of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: adamnaj@pennmedicine.upenn.edu.
Honghuang LinDepartment of Medicine, Boston University School of Medicine, Boston, MA, USA.
Badri N VardarajanDepartment of Neurology, Columbia University Medical Center, New York, NY, USA.
Simon WhiteHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
Daniel LancourDepartment of Biomedical Genetics, Boston University School of Medicine, Boston, MA, USA.
Yiyi MaDepartment of Biomedical Genetics, Boston University School of Medicine, Boston, MA, USA.
Michael SchmidtJohn P. Hussman Institute for Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.
Fangui SunDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Mariusz ButkiewiczDepartment of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
William S BushDepartment of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
Brian W KunkleJohn P. Hussman Institute for Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.
John MalamonDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Najaf AminDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Seung Hoan ChoiDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Kara L Hamilton-NelsonJohn P. Hussman Institute for Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.
Sven J van der LeeDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Namrata GuptaMedical and Population Genetics Program, Broad Institute, Cambridge, MA, USA.
Daniel C KoboldtInstitute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
Mohamad SaadDepartment of Biostatistics, University of Washington, Seattle, WA, USA; Division of Medical Genetics, University of Washington, Seattle, WA, USA.
Bowen WangDepartment of Statistics, University of Washington, Seattle, WA, USA.
Alejandro Q NatoDivision of Medical Genetics, University of Washington, Seattle, WA, USA.
Harkirat K SohiDivision of Medical Genetics, University of Washington, Seattle, WA, USA.
Amanda KuzmaDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Alzheimer's Disease Sequencing Project (ADSP)
Li-San WangDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
L Adrienne CupplesDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA; The Framingham Heart Study, Framingham, MA, USA.
Cornelia van DuijnDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Sudha SeshadriThe Framingham Heart Study, Framingham, MA, USA; Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
Gerard D SchellenbergDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Eric BoerwinkleHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA; Human Genetics Center, University of Texas Health Science Center, Houston, TX, USA.
Joshua C BisCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
Josée DupuisDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA; The Framingham Heart Study, Framingham, MA, USA.
William J SalernoHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
Ellen M WijsmanDepartment of Biostatistics, University of Washington, Seattle, WA, USA; Division of Medical Genetics, University of Washington, Seattle, WA, USA.
Eden R MartinJohn P. Hussman Institute for Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.
Anita L DeStefanoDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA; The Framingham Heart Study, Framingham, MA, USA; Department of Neurology, Boston University School of Medicine, Boston, MA, USA.

Funding

Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6M
Large Scale Genome SequencingU54HG003079 · NHGRI · WASHINGTON UNIVERSITY · PI DUTCHER, SUSAN K · 2004 to 2016
$445.7M
The Human Genome Sequencing CenterU54HG003273 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI GIBBS, RICHARD A · 2004 to 2015
$341.3M
National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8M
NATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8M
Alzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4M
THERAPEUTIC EFFECTS OF INTRA-NASAL INSULIN DETEMIRP50AG005136 · NIA · UNIVERSITY OF WASHINGTON · PI GRABOWSKI, THOMAS J. · 1985 to 2019
$57.2M
Satellite Diagnostic and Treatment Clinic CoreP50AG008702 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DE JAGER, PHILIP L · 1989 to 2019
$46.3M
National Alzheimer's Coordinating CenterU24AG072122 · NIA · UNIVERSITY OF WASHINGTON · PI STEPHENS, KARI A · 2021 to 2025
$45.8M
THE NIA GENETICS OF ALZHEIMER'S DISEASE DATA STORAGE SITEU24AG041689 · NIA · UNIVERSITY OF PENNSYLVANIA · PI LI-SAN WANG · 2012 to 2026
$42.3M
Genome Center for Alzheimer's Disease (GCAD)U54AG052427 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID, WANG, LI-SAN · 2016 to 2025
$32.8M
UC Davis Alzheimer's Disease Core CenterP30AG010129 · NIA · UNIVERSITY OF CALIFORNIA DAVIS · PI DECARLI, CHARLES · 1991 to 2020
$28.3M
NHGRI NIH HHS U54 HG003067NHGRI NIH HHS U54 HG003079NHGRI NIH HHS U54 HG003273NHLBI NIH HHS HHSN268201100005CNHLBI NIH HHS HHSN268201100006CNHLBI NIH HHS HHSN268201100007CNHLBI NIH HHS HHSN268201100008CNHLBI NIH HHS HHSN268201100009CNHLBI NIH HHS HHSN268201100010CNHLBI NIH HHS HHSN268201100011CNHLBI NIH HHS HHSN268201100012CNHLBI NIH HHS R01 HL105756NHLBI NIH HHS RC2 HL102419NIA NIH HHS P30 AG010129NIA NIH HHS P30 AG066546NIA NIH HHS P50 AG005136NIA NIH HHS P50 AG008702NIA NIH HHS R01 AG033193NIA NIH HHS R01 AG054060NIA NIH HHS R01 AG054076NIA NIH HHS U01 AG016976NIA NIH HHS U01 AG032984NIA NIH HHS U01 AG049505NIA NIH HHS U01 AG049507NIA NIH HHS U01 AG049508NIA NIH HHS U01 AG052409NIA NIH HHS U01 AG058654NIA NIH HHS U01 AG062602NIA NIH HHS U24 AG021886NIA NIH HHS U24 AG041689NIA NIH HHS U24 AG072122NIA NIH HHS U54 AG052427NIA NIH HHS UF1 AG047133NINDS NIH HHS R01 NS017950
6 · The paper itself

Abstract

The Alzheimer's Disease Sequencing Project (ADSP) performed whole genome sequencing (WGS) of 584 subjects from 111 multiplex families at three sequencing centers. Genotype calling of single nucleotide variants (SNVs) and insertion-deletion variants (indels) was performed centrally using GATK-HaplotypeCaller and Atlas V2. The ADSP Quality Control (QC) Working Group applied QC protocols to project-level variant call format files (VCFs) from each pipeline, and developed and implemented a novel protocol, termed "consensus calling," to combine genotype calls from both pipelines into a single high-quality set. QC was applied to autosomal bi-allelic SNVs and indels, and included pipeline-recommended QC filters, variant-level QC, and sample-level QC. Low-quality variants or genotypes were excluded, and sample outliers were noted. Quality was assessed by examining Mendelian inconsistencies (MIs) among 67 parent-offspring pairs, and MIs were used to establish additional genotype-specific filters for GATK calls. After QC, 578 subjects remained. Pipeline-specific QC excluded ~12.0% of GATK and 14.5% of Atlas SNVs. Between pipelines, ~91% of SNV genotypes across all QCed variants were concordant; 4.23% and 4.56% of genotypes were exclusive to Atlas or GATK, respectively; the remaining ~0.01% of discordant genotypes were excluded. For indels, variant-level QC excluded ~36.8% of GATK and 35.3% of Atlas indels. Between pipelines, ~55.6% of indel genotypes were concordant; while 10.3% and 28.3% were exclusive to Atlas or GATK, respectively; and ~0.29% of discordant genotypes were. The final WGS consensus dataset contains 27,896,774 SNVs and 3,133,926 indels and is publicly available.

Indexed as

Quality ControlAlgorithmsAlzheimer DiseaseFemaleGenome-Wide Association StudyGenotypeGenotyping TechniquesHumansMalePolymorphism, GeneticWhole Genome SequencingAtlasConsensus callingGATKMendelian inconsistenciesQuality controlWhole genome sequencing

Identifiers

PMID29857119
PMCPMC6397097

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.