Evidence mapPaperPMID 41565855Full record

ArticleNature genetics2026

Multi-trait and multi-ancestry genetic analysis of comorbid lung diseases and traits improves genetic discovery and polygenic risk prediction.

Yixuan He, Wenhan Lu, Yon Ho Jee, Mu-Yi Shih, Ying Wang, Kristin Tsuo, David C Qian, James A Diao, Hailiang Huang, Chirag J Patel and 8 more

Abstract read
In one paragraph

Article in Nature genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Yixuan HeAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA. yixuan.he@uth.tmc.edu.ORCID 0000-0003-4033-6513
Wenhan LuAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0002-3048-9658
Yon Ho JeeAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0003-4686-2186
Mu-Yi ShihDepartment of Public Health & Institute of Health Data Analytics and Statistics, College of Public Health, National Taiwan University, Taipei, Taiwan.
Ying WangAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0001-7808-6279
Kristin TsuoAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
David C QianDepartment of Thoracic Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID 0000-0002-8459-009X
James A DiaoDepartment of Medicine, Harvard Medical School, Boston, MA, USA.
Hailiang HuangAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0003-1461-5762
Chirag J PatelDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-8756-8525
Jinyoung ByunInstitute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA.ORCID 0000-0001-8579-1435
Bogdan PasaniucDepartment of Genetics, University of Pennsylvania, Philadelphia, PA, USA.
Elizabeth G AtkinsonDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.ORCID 0000-0002-6308-776X
Christopher I AmosInstitute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA.ORCID 0000-0002-8540-7023
Yen-Chen Anne FengDepartment of Public Health & Institute of Health Data Analytics and Statistics, College of Public Health, National Taiwan University, Taipei, Taiwan.
Matthew MollChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Michael H ChoChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.ORCID 0000-0002-4907-1657
Alicia R MartinAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA. armartin@broadinstitute.org.ORCID 0000-0003-0241-3522

Funding

Genetic and Genomic Characterization of the Occurrence and Progression of Interstitial Lung AbnormalitiesR01HL135142 · BRIGHAM AND WOMEN'S HOSPITAL · 2025 to 2025
$1.5M
Uncovering the genetically-driven differential susceptibility to chronic obstructive pulmonary disease and pulmonary fibrosisR01HL162813 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · 2024 to 2025
$1.5M
Enabling improved applicability and transferability of polygenic scores across populationsU01HG011719 · MASSACHUSETTS GENERAL HOSPITAL · 2025 to 2025
$983k
Deciphering respiratory disease mechanisms through integration of genomic and functional data across massive global biobanksR01HL179112 · MASSACHUSETTS GENERAL HOSPITAL · 2025 to 2025
$806k
Sequencing Familial Lung CancerR01CA243483 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Christopher I. Amos, Susan Mengel Pinney · 2023 to 2023
$711k
Identifying Subtypes of COPD Using Metabolomic and Genomic ApproachesR01HL168199 · BRIGHAM AND WOMEN'S HOSPITAL · 2025 to 2025
$698k
Cataloging multi-ancestry 'omic readouts of the environmental and genetic determinants of type 2 diabetesR01DK137993 · HARVARD MEDICAL SCHOOL · 2025 to 2025
$670k
Data science tools to identify robust exposure-phenotype associations for precision medicineR01ES032470 · HARVARD MEDICAL SCHOOL · 2025 to 2025
$620k
Mass General Brigham Training Program in Precision and Genomic MedicineT32HG010464 · MASSACHUSETTS GENERAL HOSPITAL · 2025 to 2025
$477k
Integrating Genetics and Socio-Environmental Factors to Predict Disease ProgressionK99HG013969 · MASSACHUSETTS GENERAL HOSPITAL · 2025 to 2025
$138k
NCI NIH HHS R01 CA243483NCI NIH HHS U19 CA203654NHGRI NIH HHS K99 HG013969NHGRI NIH HHS T32 HG010464NHGRI NIH HHS U01 HG011719NHLBI NIH HHS R01 HL135142NHLBI NIH HHS R01 HL153248NHLBI NIH HHS R01 HL162813NHLBI NIH HHS R01 HL168199NHLBI NIH HHS R01 HL179112NIDDK NIH HHS R01 DK137993NIEHS NIH HHS R01 ES032470NIMH NIH HHS R00 MH117229U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA243483U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) U19CA203654U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL135142U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL153248U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL162813U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL168199U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL179112U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) K99HG013969U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) T32HG010464U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) U01HG011719U.S. Department of Health & Human Services | NIH | National Institute of Environmental Health Sciences (NIEHS) R01DK137993U.S. Department of Health & Human Services | NIH | National Institute of Environmental Health Sciences (NIEHS) R01ES032470U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) K99/R00MH117229
6 · The paper itself

Abstract

While respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma share many risk factors, most studies investigate them in isolation and in predominantly European-ancestry populations. Here, we conducted the most powerful multi-trait and multi-ancestry genetic analysis of respiratory diseases and auxiliary traits to date, identifying 25 new loci associated with lung function in individuals of East Asian ancestry. Using these results, we developed PRSxtra (cross-trait and cross-ancestry), a multi-trait and multi-ancestry polygenic risk score (PRS) approach that leverages shared components of heritable risk via pleiotropic effects. PRSxtra significantly improved the prediction of asthma, COPD and lung cancer compared to trait- and ancestry-matched PRSs in a multi-ancestry cohort from the All of Us Research Program, especially in diverse populations. Our results present a new framework for multi-trait and multi-ancestry studies of respiratory diseases to improve genetic discovery and polygenic prediction.

Indexed as

Genetic Predisposition to DiseaseLung DiseasesMultifactorial InheritanceAsthmaComorbidityEast Asian PeopleEuropean PeopleGenetic Risk ScoreGenome-Wide Association StudyHumansLung NeoplasmsPolymorphism, Single NucleotidePulmonary Disease, Chronic ObstructiveRisk Factors

Identifiers

PMID41565855
PMCPMC13284852

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.