Evidence map›Paper›PMID 36269708›Full record

ArticlePloS one2022

Genome-wide discovery for diabetes-dependent triglycerides-associated loci.

Margaret Sunitha Selvaraj, Kaavya Paruchuri, Sara Haidermota, Rachel Bernardo, Stephen S Rich, Gina M Peloso, Pradeep Natarajan

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.2field-weighted citation impact, top 11% 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

7 citing papers in PubMed, 13 citations in OpenAlex.

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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

7 authors at 3 institutions in 1 country.

Margaret Sunitha SelvarajCardiovascular Research Center, Massachusetts General Hospital, Boston, MA, United States of America.ORCID 0000-0002-2751-9254
Kaavya ParuchuriCardiovascular Research Center, Massachusetts General Hospital, Boston, MA, United States of America.ORCID 0000-0003-1228-1674
Sara HaidermotaCardiovascular Research Center, Massachusetts General Hospital, Boston, MA, United States of America.
Rachel BernardoCardiovascular Research Center, Massachusetts General Hospital, Boston, MA, United States of America.ORCID 0000-0001-7139-6899
Stephen S RichCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, United States of America.ORCID 0000-0003-3872-7793
Gina M PelosoDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, United States of America.ORCID 0000-0002-5355-8636
Pradeep NatarajanCardiovascular Research Center, Massachusetts General Hospital, Boston, MA, United States of America.ORCID 0000-0001-8402-7435
Broad Institute · USBoston University · USUniversity of Virginia · US

Funding

Polygenic Risk Scores for Diverse Populations - Bridging Research and Clinical CareR01HL151152 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Christy Leigh Avery, Jennifer Below · 2020 to 2026
$12.3M
Using genetic variation to study biology of blood lipids & coronary heart diseaseR01HL127564 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Pradeep Natarajan, Gina Marie Peloso · 2015 to 2026
$7.3M
Clonal hematopoiesis in the Womens Health Initiative Memory StudyR01HL148565 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI ALEXANDER P REINER, Eric A. Whitsel · 2019 to 2026
$5.9M
Clonal hematopoiesis in humans: determinants of development and progressionR01HL148050 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI BALLANTYNE, CHRISTIE MITCHELL, NATARAJAN, PRADEEP · 2019 to 2022
$5.9M
Whole genome sequences in individuals to comprehensively characterize the genetic mechanisms of dyslipidemiasR01HL142711 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Satoshi Koyama, Gina Marie Peloso · 2019 to 2026
$4.7M
CLONAL HEMATOPOIESIS OF INDETERMINATE POTENTIAL IN CHRONIC KIDNEY DISEASE PATIENTSR01DK125782 · NIDDK · UNIVERSITY OF ILLINOIS AT CHICAGO · PI KELLY, TANIKA NICOLE · 2021 to 2025
$3.3M
Clonal hematopoiesis of indeterminate potential and HIV in the REPRIEVE trialR01HL151283 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI NATARAJAN, PRADEEP · 2020 to 2023
$2.5M
Medical Research Council MC_PC_17228Medical Research Council MC_QA137853NHLBI NIH HHS R01 HL127564NHLBI NIH HHS R01 HL142711NHLBI NIH HHS R01 HL148050NHLBI NIH HHS R01 HL148565NHLBI NIH HHS R01 HL151152NHLBI NIH HHS R01 HL151283NIDDK NIH HHS R01 DK125782
6 · The paper itself

Abstract

purposeWe aimed to discover loci associated with triglyceride (TG) levels in the context of type 2 diabetes (T2D). We conducted a genome-wide association study (GWAS) in 424,120 genotyped participants of the UK Biobank (UKB) with T2D status and TG levels.

methodsWe stratified the cohort based on T2D status and conducted association analyses of TG levels for genetic variants with minor allele count (MAC) at least 20 in each stratum. Effect differences of genetic variants by T2D status were determined by Cochran's Q-test and we validated the significantly associated variants in the Mass General Brigham Biobank (MGBB).

resultsAmong 21,176 T2D and 402,944 non-T2D samples from UKB, stratified GWAS identified 19 and 315 genomic risk loci significantly associated with TG levels, respectively. Only chr6p21.32 exhibited genome-wide significant heterogeneity (I2 = 98.4%; pheterogeneity = 2.1x10-15), with log(TG) effect estimates of -0.066 (95%CI: -0.082, -0.050) and 0.002 (95%CI: -0.002, 0.006) for T2D and non-T2D, respectively. The lead variant rs9274619:A (allele frequency 0.095) is located 2Kb upstream of the HLA-DQB1 gene, between HLA-DQB1 and HLA-DQA2 genes. We replicated this finding among 25,137 participants (6,951 T2D cases) of MGBB (pheterogeneity = 9.5x10-3). Phenome-wide interaction association analyses showed that the lead variant was strongly associated with a concomitant diagnosis of type 1 diabetes (T1D) as well as diabetes-associated complications.

conclusionIn conclusion, we identified an intergenic variant near HLA-DQB1/DQA2 significantly associates with decreased triglycerides only among those with T2D and highlights an immune overlap with T1D.

Indexed as

Diabetes Mellitus, Type 1Diabetes Mellitus, Type 2TriglyceridesGenome-Wide Association StudyHumansMitoguazonePolymorphism, Single Nucleotidemethylglyoxal bis(butylamidinohydrazone)MitoguazoneTriglycerides

Identifiers

PMID36269708
PMCPMC9586367
OpenAlexW4307002941

What Socratic holds

Textmetadata
LicenceCC BY
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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.