Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
QIMR Home Page
GenEpi Home Page
About GenEpi
Publications
Contacts
Research
Staff Index
Collaborators
Software Tools
Computing Resources
Studies
Search
GenEpi Intranet
PMID
23063622
TITLE
Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.
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.
Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
DATE PUBLISHED
2012 Nov 2
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2012/05/12
revised 2012/08/02
accepted 2012/08/30
aheadofprint 2012/10/11
entrez 2012/10/16 06:00
pubmed 2012/10/16 06:00
medline 2013/01/15 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Asselbergs FW Asselbergs Folkert W FW Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
Guo Y Guo Yiran Y
van Iperen EP van Iperen Erik P A EP
Sivapalaratnam S Sivapalaratnam Suthesh S
Tragante V Tragante Vinicius V
Lanktree MB Lanktree Matthew B MB
Lange LA Lange Leslie A LA
Almoguera B Almoguera Berta B
Appelman YE Appelman Yolande E YE
Barnard J Barnard John J
Baumert J Baumert Jens J
Beitelshees AL Beitelshees Amber L AL
Bhangale TR Bhangale Tushar R TR
Chen YD Chen Yii-Der Ida YD
Gaunt TR Gaunt Tom R TR
Gong Y Gong Yan Y
Hopewell JC Hopewell Jemma C JC
Johnson T Johnson Toby T
Kleber ME Kleber Marcus E ME
Langaee TY Langaee Taimour Y TY
Li M Li Mingyao M
Li YR Li Yun R YR
Liu K Liu Kiang K
McDonough CW McDonough Caitrin W CW
Meijs MF Meijs Matthijs F L MF
Middelberg RP Middelberg Rita P S RP
Musunuru K Musunuru Kiran K
Nelson CP Nelson Christopher P CP
O'Connell JR O'Connell Jeffery R JR
Padmanabhan S Padmanabhan Sandosh S
Pankow JS Pankow James S JS
Pankratz N Pankratz Nathan N
Rafelt S Rafelt Suzanne S
Rajagopalan R Rajagopalan Ramakrishnan R
Romaine SP Romaine Simon P R SP
Schork NJ Schork Nicholas J NJ
Shaffer J Shaffer Jonathan J
Shen H Shen Haiqing H
Smith EN Smith Erin N EN
Tischfield SE Tischfield Sam E SE
van der Most PJ van der Most Peter J PJ
van Vliet-Ostaptchouk JV van Vliet-Ostaptchouk Jana V JV
Verweij N Verweij Niek N
Volcik KA Volcik Kelly A KA
Zhang L Zhang Li L
Bailey KR Bailey Kent R KR
Bailey KM Bailey Kristian M KM
Bauer F Bauer Florianne F
Boer JM Boer Jolanda M A JM
Braund PS Braund Peter S PS
Burt A Burt Amber A
Burton PR Burton Paul R PR
Buxbaum SG Buxbaum Sarah G SG
Chen W Chen Wei W
Cooper-Dehoff RM Cooper-Dehoff Rhonda M RM
Cupples LA Cupples L Adrienne LA
deJong JS deJong Jonas S JS
Delles C Delles Christian C
Duggan D Duggan David D
Fornage M Fornage Myriam M
Furlong CE Furlong Clement E CE
Glazer N Glazer Nicole N
Gums JG Gums John G JG
Hastie C Hastie Claire C
Holmes MV Holmes Michael V MV
Illig T Illig Thomas T
Kirkland SA Kirkland Susan A SA
Kivimaki M Kivimaki Mika M
Klein R Klein Ronald R
Klein BE Klein Barbara E BE
Kooperberg C Kooperberg Charles C
Kottke-Marchant K Kottke-Marchant Kandice K
Kumari M Kumari Meena M
LaCroix AZ LaCroix Andrea Z AZ
Mallela L Mallela Laya L
Murugesan G Murugesan Gurunathan G
Ordovas J Ordovas Jose J
Ouwehand WH Ouwehand Willem H WH
Post WS Post Wendy S WS
Saxena R Saxena Richa R
Scharnagl H Scharnagl Hubert H
Schreiner PJ Schreiner Pamela J PJ
Shah T Shah Tina T
Shields DC Shields Denis C DC
Shimbo D Shimbo Daichi D
Srinivasan SR Srinivasan Sathanur R SR
Stolk RP Stolk Ronald P RP
Swerdlow DI Swerdlow Daniel I DI
Taylor HA Jr Taylor Herman A HA
Topol EJ Topol Eric J EJ
Toskala E Toskala Elina E
van Pelt JL van Pelt Joost L JL
van Setten J van Setten Jessica J
Yusuf S Yusuf Salim S
Whittaker JC Whittaker John C JC
Zwinderman AH Zwinderman A H AH
LifeLines Cohort Study
Anand SS Anand Sonia S SS
Balmforth AJ Balmforth Anthony J AJ
Berenson GS Berenson Gerald S GS
Bezzina CR Bezzina Connie R CR
Boehm BO Boehm Bernhard O BO
Boerwinkle E Boerwinkle Eric E
Casas JP Casas Juan P JP
Caulfield MJ Caulfield Mark J MJ
Clarke R Clarke Robert R
Connell JM Connell John M JM
Cruickshanks KJ Cruickshanks Karen J KJ
Davidson KW Davidson Karina W KW
Day IN Day Ian N M IN
de Bakker PI de Bakker Paul I W PI
Doevendans PA Doevendans Pieter A PA
Dominiczak AF Dominiczak Anna F AF
Hall AS Hall Alistair S AS
Hartman CA Hartman Catharina A CA
Hengstenberg C Hengstenberg Christian C
Hillege HL Hillege Hans L HL
Hofker MH Hofker Marten H MH
Humphries SE Humphries Steve E SE
Jarvik GP Jarvik Gail P GP
Johnson JA Johnson Julie A JA
Kaess BM Kaess Bernhard M BM
Kathiresan S Kathiresan Sekar S
Koenig W Koenig Wolfgang W
Lawlor DA Lawlor Debbie A DA
März W März Winfried W
Melander O Melander Olle O
Mitchell BD Mitchell Braxton D BD
Montgomery GW Montgomery Grant W GW
Munroe PB Munroe Patricia B PB
Murray SS Murray Sarah S SS
Newhouse SJ Newhouse Stephen J SJ
Onland-Moret NC Onland-Moret N Charlotte NC
Poulter N Poulter Neil N
Psaty B Psaty Bruce B
Redline S Redline Susan S
Rich SS Rich Stephen S SS
Rotter JI Rotter Jerome I JI
Schunkert H Schunkert Heribert H
Sever P Sever Peter P
Shuldiner AR Shuldiner Alan R AR
Silverstein RL Silverstein Roy L RL
Stanton A Stanton Alice A
Thorand B Thorand Barbara B
Trip MD Trip Mieke D MD
Tsai MY Tsai Michael Y MY
van der Harst P van der Harst Pim P
van der Schoot E van der Schoot Ellen E
van der Schouw YT van der Schouw Yvonne T YT
Verschuren WM Verschuren W M Monique WM
Watkins H Watkins Hugh H
Wilde AA Wilde Arthur A M AA
Wolffenbuttel BH Wolffenbuttel Bruce H R BH
Whitfield JB Whitfield John B JB
Hovingh GK Hovingh G Kees GK
Ballantyne CM Ballantyne Christie M CM
Wijmenga C Wijmenga Cisca C
Reilly MP Reilly Muredach P MP
Martin NG Martin Nicholas G NG
Wilson JG Wilson James G JG
Rader DJ Rader Daniel J DJ
Samani NJ Samani Nilesh J NJ
Reiner AP Reiner Alex P AP
Hegele RA Hegele Robert A RA
Kastelein JJ Kastelein John J P JJ
Hingorani AD Hingorani Aroon D AD
Talmud PJ Talmud Philippa J PJ
Hakonarson H Hakonarson Hakon H
Elbers CC Elbers Clara C CC
Keating BJ Keating Brendan J BJ
Drenos F Drenos Fotios F
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
de Boer Rudolf R
Hillege Hans H
van der Klauw Melanie M
Navis Gerjan G
Ormel Hans H
Postma Dirkje D
Rosmalen Judith J
Slaets Joris J
Stolk Ronald R
Wolffenbuttel Bruce B
Alizadeh Behrooz B
Boezen Marike M
Bruinenberg Marcel M
Festen Noortje N
Franke Lude L
van der Harst Pim P
Navis Gerjan G
Postma Dirkje D
Snieder Harold H
Wijmenga Cisca C
Wolffenbuttel Bruce B
JOURNAL
VOLUME: 91
ISSUE: 5
TITLE: American journal of human genetics
ISOABBREVIATION: Am. J. Hum. Genet.
YEAR: 2012
MONTH: Nov
DAY: 2
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1537-6605
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Am J Hum Genet
COUNTRY: United States
ISSNLINKING: 0002-9297
NLMUNIQUEID: 0370475
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
Cites Stat Med. 2002 Jun 15;21(11):1539-58 12111919
Cites Arterioscler Thromb Vasc Biol. 2003 Feb 1;23(2):160-7 12588754
Cites J Biol Chem. 2003 Mar 14;278(11):9869-74 12522134
Cites BMJ. 2003 Jun 28;326(7404):1423 12829554
Cites Eur J Cardiovasc Nurs. 2003 Apr;2(1):7-18 14622644
Cites Neurology. 2004 Mar 9;62(5):811-4 15007140
Cites JAMA. 2009 Nov 11;302(18):1993-2000 19903920
Cites Am J Hum Genet. 2009 Nov;85(5):628-42 19913121
Cites N Engl J Med. 2009 Dec 24;361(26):2518-28 20032323
Cites Circ Cardiovasc Genet. 2010 Apr;3(2):147-54 20124441
Cites Nat Genet. 2010 Jul;42(7):565-9 20562875
Cites Nature. 2010 Aug 5;466(7307):703-4 20686562
Cites Gastroenterology. 1991 Nov;101(5):1339-44 1718807
Cites Atherosclerosis. 1992 Oct;96(2-3):91-107 1466657
Cites Atherosclerosis. 1993 Dec;104(1-2):1-18 8141833
Cites Nat Genet. 1996 Jun;13(2):238-40 8640235
Cites N Engl J Med. 1998 Jun 4;338(23):1650-6 9614255
Cites Comp Biochem Physiol C Toxicol Pharmacol. 2004 Dec;139(4):209-18 15683829
Cites Int J Epidemiol. 2005 Apr;34(2):251-6 15576467
Cites Am J Physiol Gastrointest Liver Physiol. 2006 Feb;290(2):G269-76 16179600
Cites Nat Genet. 2006 Feb;38(2):218-22 16429159
Cites Am J Hum Genet. 2006 Apr;78(4):629-44 16532393
Cites Lancet. 2006 May 27;367(9524):1747-57 16731270
Cites Nat Genet. 2006 Aug;38(8):904-9 16862161
Cites Curr Opin Lipidol. 2004 Jun;15(3):239-46 15166778
Cites Pflugers Arch. 2007 Feb;453(5):745-52 16440216
Cites Am J Hum Genet. 2007 Sep;81(3):559-75 17701901
Cites PLoS Genet. 2008 Jan;4(1):e236 18208327
Cites JAMA. 2008 Mar 19;299(11):1335-44 18349094
Cites Obes Rev. 2008 May;9(3):246-50 18373508
Cites Ann Hum Genet. 2008 Jul;72(Pt 4):485-98 18325082
Cites Arterioscler Thromb Vasc Biol. 2008 Oct;28(10):1838-43 18658047
Cites Hum Mol Genet. 2008 Oct 15;17(R2):R122-8 18852200
Cites PLoS One. 2008;3(10):e3583 18974833
Cites Bioinformatics. 2008 Dec 15;24(24):2938-9 18974171
Cites Nat Rev Genet. 2009 Feb;10(2):109-21 19139765
Cites PLoS Genet. 2009 Jan;5(1):e1000342 19148283
Cites Nat Rev Genet. 2009 Apr;10(4):241-51 19293820
Cites Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9362-7 19474294
Cites J Lipid Res. 2009 Jul;50(7):1487-96 19299407
Cites PLoS Genet. 2009 Jun;5(6):e1000530 19557164
Cites Lipids Health Dis. 2009;8:24 19558660
Cites Genetics. 2009 Jul;182(3):845-50 19416939
Cites Nature. 2009 Oct 8;461(7265):747-53 19812666
Cites Am J Epidemiol. 2004 Sep 1;160(5):421-9 15321838
Cites Clin Chem. 1972 Jun;18(6):499-502 4337382
Cites Proc Natl Acad Sci U S A. 1989 Jan;86(2):587-91 2563166
Cites Bioinformatics. 2010 Sep 1;26(17):2190-1 20616382
Cites Hum Mol Genet. 2010 Oct 15;19(20):3936-47 20650961
Cites Am J Hum Genet. 2011 Jan 7;88(1):6-18 21194676
Cites PLoS One. 2011;6(1):e14529 21283740
Cites Hum Genet. 2011 Mar;129(3):307-17 21153663
Cites Nat Rev Cardiol. 2011 Apr;8(4):197-206 21283149
Cites Nat Rev Cardiol. 2011 Apr;8(4):207-21 21321562
Cites Brief Bioinform. 2011 May;12(3):259-69 21546449
Cites Hum Mol Genet. 2011 Jun 1;20(11):2273-84 21378095
Cites Nat Genet. 2011 Jun;43(6):519-25 21552263
Cites PLoS Genet. 2011 Sep;7(9):e1002260 21966275
Cites Arthritis Res Ther. 2011;13(1):101 21345260
Cites Atherosclerosis. 2011 Dec;219(2):698-703 21945496
Cites Am J Hum Genet. 2011 Dec 9;89(6):688-700 22100073
Cites Diabetologia. 2012 Feb;55(2):331-9 22038522
Cites Med Clin North Am. 2012 Jan;96(1):141-54 22391258
Cites Am J Hum Genet. 2012 Mar 9;90(3):410-25 22325160
Cites PLoS One. 2012;7(4):e35651 22539988
Cites Nature. 2010 Aug 5;466(7307):707-13 20686565
Cites Arterioscler Thromb Vasc Biol. 2000 Sep;20(9):2029-31 10978244
Cites Atherosclerosis. 2000 Sep;152(1):193-201 10996355
Cites Genet Epidemiol. 2002 Jan;22(1):78-93 11754475
Cites Cell. 2002 Jan 25;108(2):171-82 11832208
GRANTS
GRANTID AGENCY COUNTRY
090532 Wellcome Trust United Kingdom
AG-16592 NIA NIH HHS United States
AG13196 NIA NIH HHS United States
CH/03/001 British Heart Foundation United Kingdom
CH/98001 British Heart Foundation United Kingdom
G0802432 Medical Research Council United Kingdom
G9521010 Medical Research Council United Kingdom
G9521010D Medical Research Council United Kingdom
HD-061437 NICHD NIH HHS United States
HD-062783 NICHD NIH HHS United States
HL36310 NHLBI NIH HHS United States
HS06516 AHRQ HHS United States
K24 HL084034 NHLBI NIH HHS United States
MC_U137686857 Medical Research Council United Kingdom
N01-HC-05187 NHLBI NIH HHS United States
N01-HC-15103 NHLBI NIH HHS United States
N01-HC-25195 NHLBI NIH HHS United States
N01-HC-35129 NHLBI NIH HHS United States
N01-HC-45134 NHLBI NIH HHS United States
N01-HC-45204 NHLBI NIH HHS United States
N01-HC-45205 NHLBI NIH HHS United States
N01-HC-48047 NHLBI NIH HHS United States
N01-HC-48048 NHLBI NIH HHS United States
N01-HC-48049 NHLBI NIH HHS United States
N01-HC-48050 NHLBI NIH HHS United States
N01-HC-55015 NHLBI NIH HHS United States
N01-HC-55016 NHLBI NIH HHS United States
N01-HC-55018 NHLBI NIH HHS United States
N01-HC-55019 NHLBI NIH HHS United States
N01-HC-55020 NHLBI NIH HHS United States
N01-HC-55021 NHLBI NIH HHS United States
N01-HC-55022 NHLBI NIH HHS United States
N01-HC-55222 NHLBI NIH HHS United States
N01-HC-75150 NHLBI NIH HHS United States
N01-HC-85079 NHLBI NIH HHS United States
N01-HC-85080 NHLBI NIH HHS United States
N01-HC-85081 NHLBI NIH HHS United States
N01-HC-85082 NHLBI NIH HHS United States
N01-HC-85083 NHLBI NIH HHS United States
N01-HC-85084 NHLBI NIH HHS United States
N01-HC-85085 NHLBI NIH HHS United States
N01-HC-85086 NHLBI NIH HHS United States
N01-HC-95095 NHLBI NIH HHS United States
N01-HC-95100 NHLBI NIH HHS United States
N01-HC-95159 NHLBI NIH HHS United States
N01-HC-95160 NHLBI NIH HHS United States
N01-HC-95161 NHLBI NIH HHS United States
N01-HC-95162 NHLBI NIH HHS United States
N01-HC-95163 NHLBI NIH HHS United States
N01-HC-95164 NHLBI NIH HHS United States
N01-HC-95165 NHLBI NIH HHS United States
N01-HC-95166 NHLBI NIH HHS United States
N01-HC-95167 NHLBI NIH HHS United States
N01-HC-95168 NHLBI NIH HHS United States
N01-HC-95169 NHLBI NIH HHS United States
P01 HL088117 NHLBI NIH HHS United States
P20 MD006899 NIMHD NIH HHS United States
P30 CA015704 NCI NIH HHS United States
P30 DK063491 NIDDK NIH HHS United States
P30 DK072488 NIDDK NIH HHS United States
P50HL81011 NHLBI NIH HHS United States
PG/02/128 British Heart Foundation United Kingdom
PG/07/131/24254 British Heart Foundation United Kingdom
PG/07/132/24256 British Heart Foundation United Kingdom
PG/07/133/24260 British Heart Foundation United Kingdom
R01 AG011099 NIA NIH HHS United States
R01 AG016592 NIA NIH HHS United States
R01 AG021917 NIA NIH HHS United States
R01 AG18728 NIA NIH HHS United States
R01 HL088119 NHLBI NIH HHS United States
R01 HL091099 NHLBI NIH HHS United States
R01 HL105756 NHLBI NIH HHS United States
R01 HL67406 NHLBI NIH HHS United States
R01-AG-028321 NIA NIH HHS United States
R01-HL-071205 NHLBI NIH HHS United States
R01-HL-076784 NHLBI NIH HHS United States
R01-HL-092577 NHLBI NIH HHS United States
R01AG021917 NIA NIH HHS United States
R01HL086694 NHLBI NIH HHS United States
R01HL087641 NHLBI NIH HHS United States
R01HL59367 NHLBI NIH HHS United States
R37 AG011099 NIA NIH HHS United States
R37AG11099 NIA NIH HHS United States
RG/07/005/23633 British Heart Foundation United Kingdom
RG/08/008 British Heart Foundation United Kingdom
RG/08/008/25291 British Heart Foundation United Kingdom
RG/10/12/28456 British Heart Foundation United Kingdom
RG/2001004 British Heart Foundation United Kingdom
SP/07/007/23671 British Heart Foundation United Kingdom
SP/08/005/25115 British Heart Foundation United Kingdom
U01 GM074492 NIGMS NIH HHS United States
U01 HL72515 NHLBI NIH HHS United States
U01-GM074492 NIGMS NIH HHS United States
U01-HL-080295 NHLBI NIH HHS United States
U01HG004402 NHGRI NIH HHS United States
U10EY06594 NEI NIH HHS United States
UL1 RR025774 NCRR NIH HHS United States
UL1 TR000064 NCATS NIH HHS United States
UL1 TR000124 NCATS NIH HHS United States
UL1 TR000135 NCATS NIH HHS United States
UL1 TR000454 NCATS NIH HHS United States
UL1 TR000454 NCATS NIH HHS United States
UL1RR025005 NCRR NIH HHS United States
Department of Health United Kingdom
Intramural NIH HHS United States
Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Cholesterol, HDL genetics
Cholesterol, LDL genetics
European Continental Ancestry Group genetics
Female genetics
Genome-Wide Association Study genetics
Genotype genetics
Humans genetics
Lipids genetics
Male genetics
Phenotype genetics
Polymorphism, Single Nucleotide genetics
Quantitative Trait Loci genetics
Sex Factors genetics
Triglycerides genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Cholesterol, HDL
0 Cholesterol, LDL
0 Lipids
0 Triglycerides
OTHER ID's
OTHERID SOURCE
PMC3487124 NLM
Designed by: GenEpi IT
Maintained by: GenEpi IT
Feedback: webmaster
Copyright © 2007 QIMR
For more information Contact Us
epiit@qimr.edu.au
Last Modified: Oct 15 2007