Evidence map›Paper›PMID 35966919›Full record

ArticleNeurology. Genetics2022

A Fast and Robust Strategy to Remove Variant-Level Artifacts in Alzheimer Disease Sequencing Project Data.

Michael E Belloy, Yann Le Guen, Sarah J Eger, Valerio Napolioni, Michael D Greicius, Zihuai He

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology. Genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 12% of its field
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

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Alzheimer's Disease Sequencing Project release 4 whole genome sequencing dataset.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  7. Alzheimer's Disease Sequencing Project Release 4 Whole Genome Sequencing Dataset.medRxiv : the preprint server for health sciences · 2024
    Article
  8. Article
  9. Novel loci for Alzheimer's disease identified by a genome-wide association study in Ashkenazi Jews.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023
    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

6 authors at 1 institution in 2 countries.

Michael E BelloyDepartment of Neurology and Neurological Sciences (M.E.B., Y.L.G., S.J.E., M.D.G., Z.H.), Stanford University, CA; Institut du Cerveau-Paris Brain Institute-ICM (Y.L.G.), France; School of Biosciences and Veterinary Medicine (V.N.), University of Camerino, Italy; and Quantitative Sciences Unit (Z.H.), Department of Medicine, Stanford University, CA.ORCID https://orcid.org/0000-0001-7748-9033
Yann Le GuenDepartment of Neurology and Neurological Sciences (M.E.B., Y.L.G., S.J.E., M.D.G., Z.H.), Stanford University, CA; Institut du Cerveau-Paris Brain Institute-ICM (Y.L.G.), France; School of Biosciences and Veterinary Medicine (V.N.), University of Camerino, Italy; and Quantitative Sciences Unit (Z.H.), Department of Medicine, Stanford University, CA.ORCID https://orcid.org/0000-0001-6649-8364
Sarah J EgerDepartment of Neurology and Neurological Sciences (M.E.B., Y.L.G., S.J.E., M.D.G., Z.H.), Stanford University, CA; Institut du Cerveau-Paris Brain Institute-ICM (Y.L.G.), France; School of Biosciences and Veterinary Medicine (V.N.), University of Camerino, Italy; and Quantitative Sciences Unit (Z.H.), Department of Medicine, Stanford University, CA.ORCID https://orcid.org/0000-0002-7407-9626
Valerio NapolioniDepartment of Neurology and Neurological Sciences (M.E.B., Y.L.G., S.J.E., M.D.G., Z.H.), Stanford University, CA; Institut du Cerveau-Paris Brain Institute-ICM (Y.L.G.), France; School of Biosciences and Veterinary Medicine (V.N.), University of Camerino, Italy; and Quantitative Sciences Unit (Z.H.), Department of Medicine, Stanford University, CA.ORCID https://orcid.org/0000-0002-4378-6838
Michael D GreiciusDepartment of Neurology and Neurological Sciences (M.E.B., Y.L.G., S.J.E., M.D.G., Z.H.), Stanford University, CA; Institut du Cerveau-Paris Brain Institute-ICM (Y.L.G.), France; School of Biosciences and Veterinary Medicine (V.N.), University of Camerino, Italy; and Quantitative Sciences Unit (Z.H.), Department of Medicine, Stanford University, CA.
Zihuai HeDepartment of Neurology and Neurological Sciences (M.E.B., Y.L.G., S.J.E., M.D.G., Z.H.), Stanford University, CA; Institut du Cerveau-Paris Brain Institute-ICM (Y.L.G.), France; School of Biosciences and Veterinary Medicine (V.N.), University of Camerino, Italy; and Quantitative Sciences Unit (Z.H.), Department of Medicine, Stanford University, CA.
Università di Camerino · IT

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
Project 1U19AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI Duygu Tosun-Turgut · 2016 to 2026
$226.7M
Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
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
TRIAL OF VALPROATE TO ATTENUATE THE PROGRESSION OF ADU01AG010483 · NIA · UNIVERSITY OF ROCHESTER · PI AISEN, PAUL S. · 1991 to 2012
$116.2M
VCID and Stroke in a Bi-racial National CohortU01NS041588 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI CUSHMAN, MARY, HOWARD, GEORGE · 2002 to 2022
$96.0M
NATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8M
Smartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS · 1985 to 2026
$69.5M
TDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2M
ARIC Neurocognitive Study (ARIC-NCS) Renewal 2023-2028U01HL096812 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI JOSEF CORESH, THOMAS H MOSLEY · 2010 to 2026
$65.7M
Austrian Science Fund FWF I 904NCI NIH HHS R01 CA129769NCRR NIH HHS KL2 RR024151NCRR NIH HHS UL1 RR029893NHGRI NIH HHS RC2 HG005605NHGRI NIH HHS U01 HG004610NHGRI NIH HHS U01 HG006375NHGRI NIH HHS U01 HG008657NHGRI NIH HHS U54 HG003067NHGRI NIH HHS U54 HG003079NHGRI NIH HHS U54 HG003273NHLBI NIH HHS HHSN268200800007CNHLBI NIH HHS HHSN268201100005CNHLBI NIH HHS HHSN268201100005GNHLBI NIH HHS HHSN268201100005INHLBI NIH HHS HHSN268201100006CNHLBI NIH HHS HHSN268201100007CNHLBI NIH HHS HHSN268201100007INHLBI NIH HHS HHSN268201100008CNHLBI NIH HHS HHSN268201100008INHLBI NIH HHS HHSN268201100009CNHLBI NIH HHS HHSN268201100009INHLBI NIH HHS HHSN268201100010CNHLBI NIH HHS HHSN268201100011CNHLBI NIH HHS HHSN268201100011INHLBI NIH HHS HHSN268201100012CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS HHSN268201500001CNHLBI NIH HHS HHSN268201500001INHLBI NIH HHS N01 HC025195NHLBI NIH HHS N01 HC055222NHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085080NHLBI NIH HHS N01 HC085081NHLBI NIH HHS N01 HC085082NHLBI NIH HHS N01 HC085083NHLBI NIH HHS N01 HC085086NHLBI NIH HHS R01 HL070825NHLBI NIH HHS R01 HL105756NHLBI NIH HHS RC2 HL102419NHLBI NIH HHS U01 HL080295NHLBI NIH HHS U01 HL096812NHLBI NIH HHS U01 HL096814NHLBI NIH HHS U01 HL096899NHLBI NIH HHS U01 HL096902NHLBI NIH HHS U01 HL096917NHLBI NIH HHS U01 HL130114NIA NIH HHS K23 AG030944NIA NIH HHS P01 AG002219NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG010491NIA NIH HHS P01 AG019724NIA NIH HHS P01 AG026276NIA NIH HHS P30 AG008017NIA NIH HHS P30 AG008051NIA NIH HHS P30 AG010124NIA NIH HHS P30 AG010129NIA NIH HHS P30 AG010133NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG012300NIA NIH HHS P30 AG013846NIA NIH HHS P30 AG013854NIA NIH HHS P30 AG019610NIA NIH HHS P30 AG028377NIA NIH HHS P30 AG028383NIA NIH HHS P30 AG035982NIA NIH HHS P30 AG049638NIA NIH HHS P30 AG053760NIA NIH HHS P30 AG062421NIA NIH HHS P30 AG062422NIA NIH HHS P30 AG062428NIA NIH HHS P30 AG062429NIA NIH HHS P30 AG062715NIA NIH HHS P30 AG066509NIA NIH HHS P30 AG066515NIA NIH HHS P50 AG005128NIA NIH HHS P50 AG005131NIA NIH HHS P50 AG005133NIA NIH HHS P50 AG005134NIA NIH HHS P50 AG005136NIA NIH HHS P50 AG005138NIA NIH HHS P50 AG005142NIA NIH HHS P50 AG005144NIA NIH HHS P50 AG005146NIA NIH HHS P50 AG005681NIA NIH HHS P50 AG008012NIA NIH HHS P50 AG008702NIA NIH HHS P50 AG016570NIA NIH HHS P50 AG016573NIA NIH HHS P50 AG016574NIA NIH HHS P50 AG016582NIA NIH HHS P50 AG023501NIA NIH HHS P50 AG025688NIA NIH HHS P50 AG033514NIA NIH HHS P50 AG047266NIA NIH HHS P50 AG047270NIA NIH HHS P50 AG047366NIA NIH HHS R01 AG009029NIA NIH HHS R01 AG009956NIA NIH HHS R01 AG011101NIA NIH HHS R01 AG011380NIA NIH HHS R01 AG012101NIA NIH HHS R01 AG013616NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG015928NIA NIH HHS R01 AG017173NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG017919NIA NIH HHS R01 AG018016NIA NIH HHS R01 AG019085NIA NIH HHS R01 AG019757NIA NIH HHS R01 AG020098NIA NIH HHS R01 AG020688NIA NIH HHS R01 AG021136NIA NIH HHS R01 AG021547NIA NIH HHS R01 AG022018NIA NIH HHS R01 AG022374NIA NIH HHS R01 AG023629NIA NIH HHS R01 AG025259NIA NIH HHS R01 AG026390NIA NIH HHS R01 AG026916NIA NIH HHS R01 AG027944NIA NIH HHS R01 AG028786NIA NIH HHS R01 AG030146NIA NIH HHS R01 AG030653NIA NIH HHS R01 AG031272NIA NIH HHS R01 AG031581NIA NIH HHS R01 AG032990NIA NIH HHS R01 AG033040NIA NIH HHS R01 AG033193NIA NIH HHS R01 AG035137NIA NIH HHS R01 AG036836NIA NIH HHS R01 AG037212NIA NIH HHS R01 AG041232NIA NIH HHS R01 AG041718NIA NIH HHS R01 AG041797NIA NIH HHS R01 AG042437NIA NIH HHS R01 AG048927NIA NIH HHS R01 AG049607NIA NIH HHS R01 AG054076NIA NIH HHS R37 AG015473NIA NIH HHS R56 AG051876NIA NIH HHS RC2 AG036502NIA NIH HHS RC2 AG036528NIA NIH HHS RC2 AG036650NIA NIH HHS RC4 AG039085NIA NIH HHS RF1 AG015473NIA NIH HHS RF1 AG051504NIA NIH HHS RF1 AG054023NIA NIH HHS RF1 AG054052NIA NIH HHS RF1 AG054074NIA NIH HHS RF1 AG058066NIA NIH HHS RF1 AG058267NIA NIH HHS U01 AG006781NIA NIH HHS U01 AG010483NIA NIH HHS U01 AG016976NIA NIH HHS U01 AG024904NIA NIH HHS U01 AG032984NIA NIH HHS U01 AG046139NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG049505NIA NIH HHS U01 AG049506NIA NIH HHS U01 AG049507NIA NIH HHS U01 AG049508NIA NIH HHS U01 AG052409NIA NIH HHS U01 AG052410NIA NIH HHS U01 AG052411NIA NIH HHS U01 AG057659NIA NIH HHS U01 AG062602NIA NIH HHS U19 AG024904NIA NIH HHS U24 AG021886NIA NIH HHS U24 AG026395NIA NIH HHS U24 AG041689NIA NIH HHS UF1 AG047133NIMHD NIH HHS P20 MD000546NIMH NIH HHS P50 MH060451NIMH NIH HHS R01 MH080295NINDS NIH HHS P01 NS026630NINDS NIH HHS P50 NS039764NINDS NIH HHS P50 NS071674NINDS NIH HHS R01 NS017950NINDS NIH HHS R01 NS029993NINDS NIH HHS R01 NS059873NINDS NIH HHS R01 NS069719NINDS NIH HHS R01 NS080820NINDS NIH HHS U01 NS041588Wellcome Trust
6 · The paper itself

Abstract

Background and Objectives: Exome sequencing (ES) and genome sequencing (GS) are expected to be critical to further elucidate the missing genetic heritability of Alzheimer disease (AD) risk by identifying rare coding and/or noncoding variants that contribute to AD pathogenesis. In the United States, the Alzheimer Disease Sequencing Project (ADSP) has taken a leading role in sequencing AD-related samples at scale, with the resultant data being made publicly available to researchers to generate new insights into the genetic etiology of AD. To achieve sufficient power, the ADSP has adapted a study design where subsets of larger AD cohorts are collected and sequenced across multiple centers, using a variety of sequencing platforms. This approach may lead to variable variant quality across sequencing centers and/or platforms. In this study, we sought to implement and evaluate filters that can be applied fast to robustly remove variant-level artifacts in the ADSP data. Methods: We implemented a robust quality control procedure to handle ADSP data. We evaluated this procedure while performing exome-wide and genome-wide association analyses on AD risk using the latest ADSP whole ES (WES) and whole GS (WGS) data releases (NG00067.v5). Results: We observed that many variants displayed large variation in allele frequencies across sequencing centers/platforms and contributed to spurious association signals with AD risk. We also observed that sequencing platform/center adjustment in association models could not fully account for these spurious signals. To address this issue, we designed and implemented variant filters that could capture and remove these center-specific/platform-specific artifactual variants. Discussion: We derived a fast and robust approach to filter variants that represent sequencing center-related or platform-related artifacts underlying spurious associations with AD risk in ADSP WES and WGS data. This approach will be important to support future robust genetic association studies on ADSP data, as well as other studies with similar designs.

Identifiers

PMID35966919
PMCPMC9372872
OpenAlexW4293279819

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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.