Evidence map›Paper›PMID 41165235›Full record

ArticleGenetic epidemiology2025

Adjustment for Genotype Imputation Uncertainty Corrects for Inflated Type I Error in Family-Based Association Testing.

Tyler R C Day, Joshua C Bis, Nicola Chapman, Alejandro Q Nato, Andrea R V R Horimoto, Harkirat Sohi, Rafael Nafikov, Elizabeth E Blue, Mohamad Saad, Ellen M Wijsman

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genetic epidemiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Tyler R C DayDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington, USA.
Joshua C BisCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.
Nicola ChapmanDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington, USA.
Alejandro Q NatoDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington, USA.
Andrea R V R HorimotoDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington, USA.
Harkirat SohiDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington, USA.
Rafael NafikovDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington, USA.
Elizabeth E BlueDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington, USA.ORCID 0000-0002-0633-0305
Mohamad SaadDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington, USA.
Ellen M WijsmanDepartment of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington, USA.ORCID 0000-0002-2725-6669

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
WV INBRE: The Inhibitor of Growth Family Member 4 (ING4) inhibits L-Type Amino Acid Transporter 1 (LAT1) expression to suppress Breast CancerP20GM103434 · NIGMS · MARSHALL UNIVERSITY · PI GARY O RANKIN · 2012 to 2026
$61.1M
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
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
The National Institute on Aging (NIA) Late Onset of Alzheimer's Disease (LOAD) Family-Based Study (FBS)U24AG056270 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Gary Wayne Beecham, TATIANA M. FOROUD · 2017 to 2026
$31.4M
University of Washington Alzheimer's Disease Research CenterP30AG066509 · NIA · UNIVERSITY OF WASHINGTON · PI Amanda D. Boyd · 2020 to 2026
$29.0M
Building on GWAS for NHLBI-disease: the CHARGE consortiumRC2HL102419 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI BOERWINKLE, ERIC A. · 2009 to 2010
$27.6M
NHGRI NIH HHS U54 HG003067NHGRI NIH HHS U54 HG003079NHGRI NIH HHS U54 HG003273NHLBI NIH HHS R01 HL105756NHLBI NIH HHS RC2 HL102419NIA NIH HHS P30 AG066509NIA NIH HHS P50 AG005136NIA NIH HHS R01 AG015473NIA NIH HHS R01 AG019085NIA NIH HHS R01 AG019757NIA NIH HHS R01 AG021547NIA NIH HHS R01 AG027944NIA NIH HHS R01 AG028786NIA NIH HHS R01 AG033193NIA NIH HHS R01 AG041797NIA NIH HHS RF1 AG054023NIA NIH HHS U01 AG032984NIA 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 AG058589NIA NIH HHS U24 AG021886NIA NIH HHS U24 AG041689NIA NIH HHS U24 AG056270NIA NIH HHS U24 AG072122NIA NIH HHS UF1 AG047133NIGMS NIH HHS P20 GM103434NINDS NIH HHS P01 NS026630NINDS NIH HHS R01 NS069719
6 · The paper itself

Abstract

Genotype imputation is a widely-used data augmentation approach that is applied to samples of related and/or unrelated individuals. Association testing may then be carried out on the complete data with commonly-used methods. This approach has typically not accounted for the mix of observed and imputed data, although recent work has noted the potential for introduction of confounding in case-control studies. In the Alzheimer's Disease Sequencing Project family sample we found severe inflation of the test statistics in logistic regression analysis following genotype imputation, even after standard covariate adjustments. Here we dissect sources of this inflation, which is driven by three factors: frequency-dependent bias in imputation-induced allele frequencies, differential measurement error, and differential genotyping rates in cases versus controls that introduces confounding. To address the problem, we propose a statistic, imputation deviance (

Indexed as

Genome-Wide Association StudyGenotypeAlzheimer DiseaseCase-Control StudiesFamilyGene FrequencyHumansLogistic ModelsModels, GeneticPolymorphism, Single NucleotideUncertaintydata augmentationgenomic controlGWASmissing datamixed modelPedigreeWGS

Identifiers

PMID41165235
PMCPMC13265118

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Registered trials

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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.