Evidence map›Paper›PMID 35653334›Full record

SynthesisPLoS genetics2022

A multi-population phenome-wide association study of genetically-predicted height in the Million Veteran Program.

Sridharan Raghavan, Jie Huang, Catherine Tcheandjieu, Jennifer E Huffman, Elizabeth Litkowski, Chang Liu, Yuk-Lam A Ho, Haley Hunter-Zinck, Hongyu Zhao, Eirini Marouli and 15 more

Open access · goldAbstract readMeta-Analysis
In one paragraph

Synthesis in PLoS genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
3.7field-weighted citation impact, top 6% 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

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.

  1. Height, Autoimmune Thyroid Disease, and Thyroid Cancer: A Mendelian Randomization Study.Thyroid : official journal of the American Thyroid Association · 2023
    Pooled it
  2. Trial
  3. Review
  4. Article
  5. Article
  6. Article
  7. The genetic basis of human height.Nature reviews. Genetics · 2025
    Review
  8. Heightened interest in the human X and Y chromosomes.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  9. Article
  10. Article
  11. 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

25 authors at 12 institutions in 3 countries.

Sridharan RaghavanMedicine Service, Veterans Affairs Eastern Colorado Health Care System, Aurora, Colorado, United States of America.ORCID 0000-0003-0643-4873
Jie HuangSchool of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen, Guangdong, China.ORCID 0000-0002-9441-4698
Catherine TcheandjieuVeterans Affairs Palo Alto Health Care System, Palo Alto, California, United States of America.ORCID 0000-0001-9559-4339
Jennifer E HuffmanVeterans Affairs Boston Healthcare System, Boston, Massachusetts, United States of America.ORCID 0000-0002-9672-2491
Elizabeth LitkowskiMedicine Service, Veterans Affairs Eastern Colorado Health Care System, Aurora, Colorado, United States of America.ORCID 0000-0002-7079-696X
Chang LiuAtlanta Veterans Affairs Medical Center, Atlanta, Georgia, United States of America.ORCID 0000-0002-8918-7224
Yuk-Lam A HoVeterans Affairs Boston Healthcare System, Boston, Massachusetts, United States of America.ORCID 0000-0003-3305-3830
Haley Hunter-ZinckVeterans Affairs Boston Healthcare System, Boston, Massachusetts, United States of America.ORCID 0000-0001-5853-3668
Hongyu ZhaoVeterans Affairs Connecticut Healthcare System, West Haven, Connecticut, United States of America.ORCID 0000-0003-1195-9607
Eirini MarouliWilliam Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.ORCID 0000-0001-6179-1609
Kari E NorthDepartment of Epidemiology, Gillings School of Public Health, University of North Carolina, Chapel Hill, North Carolina, United States of America.
VA Million Veteran Program
Ethan LangeDepartment of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
Leslie A LangeDepartment of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
Benjamin F VoightCorporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, United States of America.
J Michael GazianoVeterans Affairs Boston Healthcare System, Boston, Massachusetts, United States of America.
Saiju PyarajanVeterans Affairs Boston Healthcare System, Boston, Massachusetts, United States of America.ORCID 0000-0002-9047-3762
Elizabeth R HauserCooperative Studies Program Epidemiology Center- Durham, Durham Veterans Affairs Health Care System, Durham, North Carolina, United States of America.ORCID 0000-0003-0367-9189
Philip S TsaoVeterans Affairs Palo Alto Health Care System, Palo Alto, California, United States of America.ORCID 0000-0001-7274-9318
Peter W F WilsonAtlanta Veterans Affairs Medical Center, Atlanta, Georgia, United States of America.ORCID 0000-0002-5653-7056
Kyong-Mi ChangCorporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, United States of America.ORCID 0000-0001-6811-9364
Kelly ChoVeterans Affairs Boston Healthcare System, Boston, Massachusetts, United States of America.ORCID 0000-0003-1727-7076
Christopher J O'DonnellVeterans Affairs Boston Healthcare System, Boston, Massachusetts, United States of America.ORCID 0000-0002-2667-8624
Yan V SunAtlanta Veterans Affairs Medical Center, Atlanta, Georgia, United States of America.ORCID 0000-0002-2838-1824
Themistocles L AssimesVeterans Affairs Palo Alto Health Care System, Palo Alto, California, United States of America.ORCID 0000-0003-2349-0009
Brigham and Women's Hospital · USEmory University · USVA Boston Healthcare System · USUniversity of Colorado Anschutz Medical Campus · USVA Eastern Colorado Health Care System · USVA Palo Alto Health Care System · USDuke University · USQueen Mary University of London · GBSouthern University of Science and Technology · CNTranslational Therapeutics (United States) · USUniversity of North Carolina at Chapel Hill · USYale University · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Leveraging multi-omics approaches to examine metabolic challenges of obesity in relation to cardiovascular diseasesR01HL143885 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI AVERY, CHRISTY LEIGH, GORDON-LARSEN, PENNY · 2019 to 2022
$8.9M
Functional Interrogation of T2D-associated genes in human stem cell-derived models and miceUM1DK126194 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI GRANT, STRUAN F A, KAESTNER, KLAUS H · 2020 to 2024
$8.8M
PAGE III: Population Architecture using Genomics and EpidemiologyR01HG010297 · NHGRI · RUTGERS, THE STATE UNIV OF N.J. · PI GIGNOUX, CHRISTOPHER R, MATISE, TARA C. · 2019 to 2022
$6.5M
Hispanic Latino Lipid ConsortiumR01HL142302 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Jennifer Below, JOSEPH MCCORMICK · 2018 to 2026
$5.8M
Integrative Approaches to Identifying Function and Clinical Significance of Adiposity Susceptibility GenesR01DK122503 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Anne Justice, Ching-Ti Liu · 2020 to 2026
$4.5M
Algorithms to identify non-coding mutational burden and disease-relevant pathwaysR01DK101478 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI VOIGHT, BENJAMIN FRANKLIN · 2014 to 2018
$2.9M
Leveraging ancestral diversity to map adiposity loci in HispanicsR01DK101855 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HAIMAN, CHRISTOPHER ALAN, LOOS, RUTH JF · 2014 to 2016
$2.1M
Statistical Methods in Trans-Omics Chronic Disease ResearchR01HG009974 · NHGRI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LIN, DANYU · 2018 to 2022
$1.5M
Algorithms to identify non-coding mutational burden and disease-relevant pathwaysR56DK101478 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI VOIGHT, BENJAMIN FRANKLIN · 2019 to 2019
$272k
Cardiovascular Disease Risk Factors, Cardiovascular Disease Risk Prediction, and Genetics in the Million Veteran ProgramI01BX004821 · VA · VETERANS HEALTH ADMINISTRATION · PI PETER WYMAN WILSON · 2020 to 2026
–
Machine Learning and Longitudinal Analyses of Metformin Response Among VeteransIK2CX001907 · VA · VA EASTERN COLORADO HEALTH CARE SYSTEM · PI RAGHAVAN, SRIDHARAN · 2019 to 2023
–
BLRD VA I01 BX003362BLRD VA I01 BX004821CSRD VA IK2 CX001907NCATS NIH HHS UL1 TR001863NHGRI NIH HHS R01 HG009974NHGRI NIH HHS R01 HG010297NHLBI NIH HHS R01 HL142302NHLBI NIH HHS R01 HL143885NIDDK NIH HHS R01 DK101478NIDDK NIH HHS R01 DK101855NIDDK NIH HHS R01 DK122503NIDDK NIH HHS R56 DK101478NIDDK NIH HHS UM1 DK126194
6 · The paper itself

Abstract

backgroundHeight has been associated with many clinical traits but whether such associations are causal versus secondary to confounding remains unclear in many cases. To systematically examine this question, we performed a Mendelian Randomization-Phenome-wide association study (MR-PheWAS) using clinical and genetic data from a national healthcare system biobank. METHODS AND

findingsAnalyses were performed using data from the US Veterans Affairs (VA) Million Veteran Program in non-Hispanic White (EA, n = 222,300) and non-Hispanic Black (AA, n = 58,151) adults in the US. We estimated height genetic risk based on 3290 height-associated variants from a recent European-ancestry genome-wide meta-analysis. We compared associations of measured and genetically-predicted height with phenome-wide traits derived from the VA electronic health record, adjusting for age, sex, and genetic principal components. We found 345 clinical traits associated with measured height in EA and an additional 17 in AA. Of these, 127 were associated with genetically-predicted height at phenome-wide significance in EA and 2 in AA. These associations were largely independent from body mass index. We confirmed several previously described MR associations between height and cardiovascular disease traits such as hypertension, hyperlipidemia, coronary heart disease (CHD), and atrial fibrillation, and further uncovered MR associations with venous circulatory disorders and peripheral neuropathy in the presence and absence of diabetes. As a number of traits associated with genetically-predicted height frequently co-occur with CHD, we evaluated effect modification by CHD status of genetically-predicted height associations with risk factors for and complications of CHD. We found modification of effects of MR associations by CHD status for atrial fibrillation/flutter but not for hypertension, hyperlipidemia, or venous circulatory disorders.

conclusionsWe conclude that height may be an unrecognized but biologically plausible risk factor for several common conditions in adults. However, more studies are needed to reliably exclude horizontal pleiotropy as a driving force behind at least some of the MR associations observed in this study.

Indexed as

Atrial FibrillationHypertensionVeteransAdultGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPolymorphism, Single Nucleotide

Identifiers

PMID35653334
PMCPMC9162317
OpenAlexW4281857359

What Socratic holds

Textmetadata
LicenceCC0
Read underepoch 390

Registered trials

None linked

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.