Evidence map›Paper›PMID 36341024›Full record

ArticleCell genomics2022

Best practices for multi-ancestry, meta-analytic transcriptome-wide association studies: Lessons from the Global Biobank Meta-analysis Initiative.

Arjun Bhattacharya, Jibril B Hirbo, Dan Zhou, Wei Zhou, Jie Zheng, Masahiro Kanai, Global Biobank Meta-analysis Initiative, Bogdan Pasaniuc, Eric R Gamazon, Nancy J Cox

Abstract read
In one paragraph

Article in Cell genomics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing 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

26 citing papers in PubMed.

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  10. Review
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  15. Fine-mapping causal tissues and genes at disease-associated loci.medRxiv : the preprint server for health sciences · 2024
    Article
  16. Improved multi-ancestry fine-mapping identifiesmedRxiv : the preprint server for health sciences · 2024
    Article
  17. Open Science Practices in Psychiatric Genetics: A Primer.Biological psychiatry global open science · 2024
    Review
  18. Article
  19. Article
  20. 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

10 authors.

Arjun BhattacharyaDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Jibril B HirboDepartment of Medicine, Division of Genetic Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
Dan ZhouDepartment of Medicine, Division of Genetic Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
Wei ZhouAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
Jie ZhengMRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK.
Masahiro KanaiAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
Global Biobank Meta-analysis Initiative
Bogdan PasaniucDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Eric R GamazonDepartment of Medicine, Division of Genetic Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
Nancy J CoxDepartment of Medicine, Division of Genetic Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.

Funding

Methods for Genome-wide Association Studies in Admixed PopulationsR01HG006399 · NHGRI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI PRICE, ALKES L · 2011 to 2024
$6.3M
Joint genomic and statistical analyses of schizophrenia and bipolar to decipher genetic susceptibilityR01MH115676 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Roel A Ophoff, Bogdan Pasaniuc · 2018 to 2026
$5.9M
PRS Center for Admixed Populations (CAPE)U01HG011715 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI Eimear Elizabeth Kenny, Leslie A Lange · 2021 to 2026
$5.2M
Analysis, Validation and Resource Creation for Genome Sequencing of Complex DiseasesU01HG009086 · NHGRI · VANDERBILT UNIVERSITY · PI COX, NANCY J, LI, BINGSHAN · 2016 to 2020
$4.3M
Collaborative multi-site project to speed the identification and management of rare genetic immune diseasesR01AI153827 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BUTTE, MANISH J, PASANIUC, BOGDAN · 2021 to 2025
$3.9M
Gene Expression Regulation in Brains of East Asian, African, and European Descent Explains Schizophrenia GWAS in Diverse Populations.R01MH126459 · NIMH · UPSTATE MEDICAL UNIVERSITY · PI Chunyu Liu · 2022 to 2026
$3.7M
Elucidation of the genetic mechanisms driving prostate tumorigenesis through integrative computational and functional approachesR01CA251555 · NCI · DANA-FARBER CANCER INST · PI FREEDMAN, MATTHEW L, PASANIUC, BOGDAN · 2021 to 2025
$3.4M
Partners Healthcare Training Program in Precision and Genomic MedicineT32HG010464 · NHGRI · MASSACHUSETTS GENERAL HOSPITAL · PI HEIDI L REHM, JORDAN W SMOLLER · 2019 to 2026
$3.1M
Haplotype-aware models of gene and isoform expression with application to genetic studies of disease in diverse populationsR01GM140287 · NIGMS · SEATTLE CHILDREN'S HOSPITAL · PI GAMAZON, ERIC R, MOHAMMADI, PEJMAN · 2021 to 2024
$2.8M
Integrative approaches for mapping the genetic risk of complex traitsR01HG009120 · NHGRI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PASANIUC, BOGDAN · 2017 to 2021
$2.3M
Functional Genomics: A Phenome-wide SurveyR35HG010718 · NHGRI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI GAMAZON, ERIC R · 2019 to 2023
$2.2M
Integration of genetic, gene expression and environmental data to inform biological basis of mammographic densityR01CA244670 · NCI · UNIVERSITY OF WASHINGTON · PI LINDSTROEM, SARA · 2021 to 2024
$1.8M
NCI NIH HHS R01 CA244670NCI NIH HHS R01 CA251555NHGRI NIH HHS K99 HG012222NHGRI NIH HHS R00 HG012222NHGRI NIH HHS R01 HG006399NHGRI NIH HHS R01 HG009120NHGRI NIH HHS R01 HG011138NHGRI NIH HHS R35 HG010718NHGRI NIH HHS T32 HG010464NHGRI NIH HHS U01 HG009086NHGRI NIH HHS U01 HG011715NIAID NIH HHS R01 AI153827NIA NIH HHS R56 AG068026NIGMS NIH HHS R01 GM140287NIMH NIH HHS R01 MH115676NIMH NIH HHS R01 MH126459
6 · The paper itself

Abstract

The Global Biobank Meta-analysis Initiative (GBMI), through its diversity, provides a valuable opportunity to study population-wide and ancestry-specific genetic associations. However, with multiple ascertainment strategies and multi-ancestry study populations across biobanks, GBMI presents unique challenges in implementing statistical genetics methods. Transcriptome-wide association studies (TWASs) boost detection power for and provide biological context to genetic associations by integrating genetic variant-to-trait associations from genome-wide association studies (GWASs) with predictive models of gene expression. TWASs present unique challenges beyond GWASs, especially in a multi-biobank, meta-analytic setting. Here, we present the GBMI TWAS pipeline, outlining practical considerations for ancestry and tissue specificity, meta-analytic strategies, and open challenges at every step of the framework. We advise conducting ancestry-stratified TWASs using ancestry-specific expression models and meta-analyzing results using inverse-variance weighting, showing the least test statistic inflation. Our work provides a foundation for adding transcriptomic context to biobank-linked GWASs, allowing for ancestry-aware discovery to accelerate genomic medicine.

Identifiers

PMID36341024
PMCPMC9631681

What Socratic holds

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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 Socratic graph.