Evidence map›Paper›PMID 30290150›Full record

ArticleAmerican journal of human genetics2018

Phenotype-Specific Enrichment of Mendelian Disorder Genes near GWAS Regions across 62 Complex Traits.

Malika Kumar Freund, Kathryn S Burch, Huwenbo Shi, Nicholas Mancuso, Gleb Kichaev, Kristina M Garske, David Z Pan, Zong Miao, Karen L Mohlke, Markku Laakso and 3 more

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

Article in American journal of human genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed, 1 pooled it
8.9field-weighted citation impact, top 2% 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

72 citing papers in PubMed, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. The genetics of hypertension.Nature reviews. Nephrology · 2026
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. A disease-specific convergence of host and Epstein-Barr virus genetics in multiple sclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  17. Article
  18. Article
  19. Article
  20. Review

12 more citing papers are in PubMed but not listed here.

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

13 authors at 3 institutions in 2 countries.

Malika Kumar FreundDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: kumarm@ucla.edu.
Kathryn S BurchBioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Huwenbo ShiBioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Nicholas MancusoDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
Gleb KichaevBioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Kristina M GarskeDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
David Z PanBioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Zong MiaoDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Karen L MohlkeDepartment of Genetics, University of North Carolina, Chapel Hill, NC, USA.
Markku LaaksoInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, 70210 Kuopio, Finland.
Päivi PajukantaDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Bogdan PasaniucDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA; Department of Computational Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Valerie A ArboledaDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA. Electronic address: varboleda@mednet.ucla.edu.
University of California, Los Angeles · USKuopio University Hospital · FIUniversity of North Carolina at Chapel Hill · US

Funding

Systems genomics of metabolic syndrome traitsP01HL028481 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LUSIS, ALDONS JAKE · 1985 to 2019
$50.2M
Training Grant in Genomic Analysis and InterpretationT32HG002536 · NHGRI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Valerie A Arboleda, Harold Pimentel · 2002 to 2026
$8.6M
Genetic epidemiology of rare and regulatory variants for metabolic traitsR01DK093757 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KAREN L. MOHLKE · 2011 to 2026
$8.2M
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
Genomics of dyslipidemia in MexicansR01HL095056 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PAJUKANTA, PAIVI · 2009 to 2018
$5.9M
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
Quantifying and Characterizing the shared genetic contribution to common cancersU01CA194393 · NCI · UNIVERSITY OF WASHINGTON · PI KRAFT, PETER, LINDSTROEM, SARA · 2015 to 2023
$3.0M
Training Grant in Neurobehavioral GeneticsT32MH073526 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BEARDEN, CARRIE E, GESCHWIND, DANIEL H · 2006 to 2020
$2.4M
Integrative approaches for mapping the genetic risk of complex traitsR01HG009120 · NHGRI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PASANIUC, BOGDAN · 2017 to 2021
$2.3M
Unraveling correlations between Mendelian and common disease using functional genomicsDP5OD024579 · OD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARBOLEDA, VALERIE A · 2017 to 2021
$1.9M
Biomedical Big Data Training GrantT32LM012424 · NLM · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PELLEGRINI, MATTEO · 2016 to 2019
$1.0M
Integrating functional genomics in primary human adipocytes to investigate gene regulatory circuitry for obesogenic cardiovascular traitsF31HL142180 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GARSKE, KRISTINA MARIE · 2018 to 2020
$110k
NCI NIH HHS U01 CA194393NHGRI NIH HHS R01 HG006399NHGRI NIH HHS R01 HG009120NHGRI NIH HHS T32 HG002536NHLBI NIH HHS F31 HL142180NHLBI NIH HHS P01 HL028481NHLBI NIH HHS R01 HL095056NIDDK NIH HHS F31 DK118865NIDDK NIH HHS R01 DK093757NIH HHS DP5 OD024579NIMH NIH HHS R01 MH115676NIMH NIH HHS T32 MH073526NLM NIH HHS T32 LM012424
6 · The paper itself

Abstract

Although recent studies provide evidence for a common genetic basis between complex traits and Mendelian disorders, a thorough quantification of their overlap in a phenotype-specific manner remains elusive. Here, we have quantified the overlap of genes identified through large-scale genome-wide association studies (GWASs) for 62 complex traits and diseases with genes containing mutations known to cause 20 broad categories of Mendelian disorders. We identified a significant enrichment of genes linked to phenotypically matched Mendelian disorders in GWAS gene sets; of the total 1,240 comparisons, a higher proportion of phenotypically matched or related pairs (n = 50 of 92 [54%]) than phenotypically unmatched pairs (n = 27 of 1,148 [2%]) demonstrated significant overlap, confirming a phenotype-specific enrichment pattern. Further, we observed elevated GWAS effect sizes near genes linked to phenotypically matched Mendelian disorders. Finally, we report examples of GWAS variants localized at the transcription start site or physically interacting with the promoters of genes linked to phenotypically matched Mendelian disorders. Our results are consistent with the hypothesis that genes that are disrupted in Mendelian disorders are dysregulated by non-coding variants in complex traits and demonstrate how leveraging findings from related Mendelian disorders and functional genomic datasets can prioritize genes that are putatively dysregulated by local and distal non-coding GWAS variants.

Indexed as

FemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMultifactorial InheritancePhenotypePolymorphism, Single NucleotidePromoter Regions, GeneticQuantitative Trait LociTranscription Initiation Sitebody mass indexcommon diseasecomplex traitsGWASHi-CMendelianmonogenicpolygenicstatistical genetics

Identifiers

PMID30290150
PMCPMC6174356
OpenAlexW2804434811

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.