Evidence map›Paper›PMID 23063622›Full record

SynthesisAmerican journal of human genetics2012

Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

Folkert W Asselbergs, Yiran Guo, Erik P A van Iperen, Suthesh Sivapalaratnam, Vinicius Tragante, Matthew B Lanktree, Leslie A Lange, Berta Almoguera, Yolande E Appelman, John Barnard and 161 more

Open access · bronzeAbstract readMeta-Analysis
In one paragraph

Synthesis in American journal of human genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 148 papers, 23 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
148citing papers in PubMed, 23 pooled it
17.8field-weighted citation impact, top 1% 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

148 citing papers in PubMed, 23 syntheses or guidelines pooled it, 268 citations in OpenAlex.

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  6. Genome-Wide Association Study HighlightsArteriosclerosis, thrombosis, and vascular biology · 2021
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88 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

171 authors at 20 institutions in 10 countries.

Folkert W AsselbergsDepartment of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
Yiran Guo
Erik P A van Iperen
Suthesh Sivapalaratnam
Vinicius Tragante
Matthew B Lanktree
Leslie A Lange
Berta Almoguera
Yolande E Appelman
John Barnard
Jens Baumert
Amber L Beitelshees
Tushar R Bhangale
Yii-Der Ida Chen
Tom R Gaunt
Yan Gong
Jemma C Hopewell
Toby Johnson
Marcus E Kleber
Taimour Y Langaee
Mingyao Li
Yun R Li
Kiang Liu
Caitrin W McDonough
Matthijs F L Meijs
Rita P S Middelberg
Kiran Musunuru
Christopher P Nelson
Jeffery R O'Connell
Sandosh Padmanabhan
James S Pankow
Nathan Pankratz
Suzanne Rafelt
Ramakrishnan Rajagopalan
Simon P R Romaine
Nicholas J Schork
Jonathan Shaffer
Haiqing Shen
Erin N Smith
Sam E Tischfield
Peter J van der Most
Jana V van Vliet-Ostaptchouk
Niek Verweij
Kelly A Volcik
Li Zhang
Kent R Bailey
Kristian M Bailey
Florianne Bauer
Jolanda M A Boer
Peter S Braund
Amber Burt
Paul R Burton
Sarah G Buxbaum
Wei Chen
Rhonda M Cooper-Dehoff
L Adrienne Cupples
Jonas S deJong
Christian Delles
David Duggan
Myriam Fornage
Clement E Furlong
Nicole Glazer
John G Gums
Claire Hastie
Michael V Holmes
Thomas Illig
Susan A Kirkland
Mika Kivimaki
Ronald Klein
Barbara E Klein
Charles Kooperberg
Kandice Kottke-Marchant
Meena Kumari
Andrea Z LaCroix
Laya Mallela
Gurunathan Murugesan
Jose Ordovas
Willem H Ouwehand
Wendy S Post
Richa Saxena
Hubert Scharnagl
Pamela J Schreiner
Tina Shah
Denis C Shields
Daichi Shimbo
Sathanur R Srinivasan
Ronald P Stolk
Daniel I Swerdlow
Herman A Taylor
Eric J Topol
Elina Toskala
Joost L van Pelt
Jessica van Setten
Salim Yusuf
John C Whittaker
A H Zwinderman
LifeLines Cohort Study
Sonia S Anand
Anthony J Balmforth
Gerald S Berenson
Connie R Bezzina
Bernhard O Boehm
Eric Boerwinkle
Juan P Casas
Mark J Caulfield
Robert Clarke
John M Connell
Karen J Cruickshanks
Karina W Davidson
Ian N M Day
Paul I W de Bakker
Pieter A Doevendans
Anna F Dominiczak
Alistair S Hall
Catharina A Hartman
Christian Hengstenberg
Hans L Hillege
Marten H Hofker
Steve E Humphries
Gail P Jarvik
Julie A Johnson
Bernhard M Kaess
Sekar Kathiresan
Wolfgang Koenig
Debbie A Lawlor
Winfried März
Olle Melander
Braxton D Mitchell
Grant W Montgomery
Patricia B Munroe
Sarah S Murray
Stephen J Newhouse
N Charlotte Onland-Moret
Neil Poulter
Bruce Psaty
Susan Redline
Stephen S Rich
Jerome I Rotter
Heribert Schunkert
Peter Sever
Alan R Shuldiner
Roy L Silverstein
Alice Stanton
Barbara Thorand
Mieke D Trip
Michael Y Tsai
Pim van der Harst
Ellen van der Schoot
Yvonne T van der Schouw
W M Monique Verschuren
Hugh Watkins
Arthur A M Wilde
Bruce H R Wolffenbuttel
John B Whitfield
G Kees Hovingh
Christie M Ballantyne
Cisca Wijmenga
Muredach P Reilly
Nicholas G Martin
James G Wilson
Daniel J Rader
Nilesh J Samani
Alex P Reiner
Robert A Hegele
John J P Kastelein
Aroon D Hingorani
Philippa J Talmud
Hakon Hakonarson
Clara C Elbers
Brendan J Keating
Fotios Drenos
University Medical Center Groningen · NLAmsterdam UMC Location University of Amsterdam · NLUniversity College London · GBUniversity Medical Center Utrecht · NLChildren's Hospital of Philadelphia · USUniversity of Florida · USUniversity of Leicester · GBUniversity of Maryland, Baltimore · USBroad Institute · USQIMR Berghofer Medical Research Institute · AUQueen Mary University of London · GBUniversity of Glasgow · GBUniversity of Leeds · GBUniversity of Minnesota · USUniversity of Washington Medical Center · USCardiovascular Institute of the South · USCleveland Clinic Lerner College of Medicine · USColumbia University · USFred Hutch Cancer Center · USHelmholtz Zentrum München · DE

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Eric Collisson · 1985 to 2026
$296.4M
Institute for Clinical and Translational Research (UL1)UL1RR025005 · NCRR · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2007 to 2011
$75.8M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
Mayo Clinic Center for Translational Science ActivitiesUL1TR000135 · NCATS · MAYO CLINIC ROCHESTER · PI KHOSLA, SUNDEEP · 2012 to 2015
$41.2M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrea L Hevener · 2003 to 2026
$40.4M
Atlanta Clinical and Translational Science Institute (ACTSI) RenewalUL1TR000454 · NCATS · EMORY UNIVERSITY · PI STEPHENS, DAVID S · 2012 to 2016
$25.8M
FAMILIAL AND BIRTH COHORT EFFECTS ON THE AGING SENSESR01AG021917 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI CRUICKSHANKS, KAREN J · 2004 to 2018
$25.2M
Genome-Wide Association Analysis in Essential Hypertension (FEHGAS study)R01HL086694 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ARAVINDA CHAKRAVARTI · 2007 to 2026
$21.2M
Pharmacogenomic Evaluation of Antihypertensive ResponsesU01GM074492 · NIGMS · UNIVERSITY OF FLORIDA · PI JOHNSON, JULIE A. · 2005 to 2014
$20.7M
IDENTIFICATION OF COMMON GENETIC VARIANTS FOR ATRIAL FIBRILLATION AND PR INTERVALR01HL092577 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI BENJAMIN, EMELIA J., ELLINOR, PATRICK THOMAS · 2009 to 2025
$20.6M
Research BaseP30DK072488 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI MITCHELL, BRAXTON D, TAYLOR, SIMEON I. · 2005 to 2019
$17.3M
THE EPIDEMIOLOGY OF AGE-RELATED OCULAR DISEASEU10EY006594 · NEI · UNIVERSITY OF WISCONSIN-MADISON · PI KLEIN, BARBARA EDEN · 1987 to 2018
$17.3M
AHRQ HHS HS06516British Heart Foundation CH/03/001British Heart Foundation CH/98001British Heart Foundation PG/02/128British Heart Foundation PG/07/131/24254British Heart Foundation PG/07/132/24256British Heart Foundation PG/07/133/24260British Heart Foundation RG/07/005/23633British Heart Foundation RG/08/008British Heart Foundation RG/08/008/25291British Heart Foundation RG/2001004British Heart Foundation SP/07/007/23671British Heart Foundation SP/08/005/25115Department of HealthIntramural NIH HHSMedical Research Council G0802432Medical Research Council G9521010Medical Research Council G9521010DMedical Research Council MC_U137686857NCATS NIH HHS UL1 TR000064NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1 TR000135NCATS NIH HHS UL1 TR000454NCI NIH HHS P30 CA015704NCRR NIH HHS UL1RR025005NCRR NIH HHS UL1 RR025774NEI NIH HHS U10EY06594NHGRI NIH HHS U01HG004402NHLBI NIH HHS HL36310NHLBI NIH HHS K24 HL084034NHLBI NIH HHS N01-HC-05187NHLBI NIH HHS N01-HC-15103NHLBI NIH HHS N01-HC-25195NHLBI NIH HHS N01-HC-35129NHLBI NIH HHS N01-HC-45134NHLBI NIH HHS N01-HC-45204NHLBI NIH HHS N01-HC-45205NHLBI NIH HHS N01-HC-48047NHLBI NIH HHS N01-HC-48048NHLBI NIH HHS N01-HC-48049NHLBI NIH HHS N01-HC-48050NHLBI NIH HHS N01-HC-55015NHLBI NIH HHS N01-HC-55016NHLBI NIH HHS N01-HC-55018NHLBI NIH HHS N01-HC-55019NHLBI NIH HHS N01-HC-55020NHLBI NIH HHS N01-HC-55021NHLBI NIH HHS N01-HC-55022NHLBI NIH HHS N01-HC-55222NHLBI NIH HHS N01-HC-75150NHLBI NIH HHS N01-HC-85079NHLBI NIH HHS N01-HC-85080NHLBI NIH HHS N01-HC-85081NHLBI NIH HHS N01-HC-85082NHLBI NIH HHS N01-HC-85083NHLBI NIH HHS N01-HC-85084NHLBI NIH HHS N01-HC-85085NHLBI NIH HHS N01-HC-85086NHLBI NIH HHS N01-HC-95095NHLBI NIH HHS N01-HC-95100NHLBI NIH HHS N01-HC-95159NHLBI NIH HHS N01-HC-95160NHLBI NIH HHS N01-HC-95161NHLBI NIH HHS N01-HC-95162NHLBI NIH HHS N01-HC-95163NHLBI NIH HHS N01-HC-95164NHLBI NIH HHS N01-HC-95165NHLBI NIH HHS N01-HC-95166NHLBI NIH HHS N01-HC-95167NHLBI NIH HHS N01-HC-95168NHLBI NIH HHS N01-HC-95169NHLBI NIH HHS P01 HL088117NHLBI NIH HHS P50HL81011NHLBI NIH HHS R01-HL-071205NHLBI NIH HHS R01-HL-076784NHLBI NIH HHS R01HL086694NHLBI NIH HHS R01HL087641NHLBI NIH HHS R01 HL088119NHLBI NIH HHS R01 HL091099NHLBI NIH HHS R01-HL-092577NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01HL59367NHLBI NIH HHS R01 HL67406NHLBI NIH HHS U01-HL-080295NHLBI NIH HHS U01 HL72515NIA NIH HHS AG13196NIA NIH HHS AG-16592NIA NIH HHS R01 AG011099NIA NIH HHS R01 AG016592NIA NIH HHS R01 AG021917NIA NIH HHS R01AG021917NIA NIH HHS R01-AG-028321NIA NIH HHS R01 AG18728NIA NIH HHS R37 AG011099NIA NIH HHS R37AG11099NICHD NIH HHS HD-061437NICHD NIH HHS HD-062783NIDDK NIH HHS P30 DK063491NIDDK NIH HHS P30 DK072488NIGMS NIH HHS U01 GM074492NIGMS NIH HHS U01-GM074492NIMHD NIH HHS P20 MD006899Wellcome Trust 090532
6 · The paper itself

Abstract

Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by a dense gene-centric approach. Our meta-analysis of 32 studies in 66,240 individuals of European ancestry was based on the custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) covering ∼2,000 candidate genes. SNP-lipid associations were replicated either in a cohort comprising an additional 24,736 samples or within the Global Lipid Genetic Consortium. We identified four, six, ten, and four unreported SNPs in established lipid genes for HDL-C, LDL-C, TC, and TGs, respectively. We also identified several lipid-related SNPs in previously unreported genes: DGAT2, HCAR2, GPIHBP1, PPARG, and FTO for HDL-C; SOCS3, APOH, SPTY2D1, BRCA2, and VLDLR for LDL-C; SOCS3, UGT1A1, BRCA2, UBE3B, FCGR2A, CHUK, and INSIG2 for TC; and SERPINF2, C4B, GCK, GATA4, INSR, and LPAL2 for TGs. The proportion of explained phenotypic variance in the subset of studies providing individual-level data was 9.9% for HDL-C, 9.5% for LDL-C, 10.3% for TC, and 8.0% for TGs. This large meta-analysis of lipid phenotypes with the use of a dense gene-centric approach identified multiple SNPs not previously described in established lipid genes and several previously unknown loci. The explained phenotypic variance from this approach was comparable to that from a meta-analysis of GWAS data, suggesting that a focused genotyping approach can further increase the understanding of heritability of plasma lipids.

Indexed as

Genome-Wide Association StudyQuantitative Trait LociCholesterol, HDLCholesterol, LDLFemaleGenotypeHumansLipidsMalePhenotypePolymorphism, Single NucleotideSex FactorsTriglyceridesWhite PeopleCholesterol, HDLCholesterol, LDLLipidsTriglycerides

Identifiers

PMID23063622
PMCPMC3487124
OpenAlexW2135185355

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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 OpenQuestion graph.