| PMID |
|
|
| TITLE |
|
| A genome-wide screen for interactions reveals a new locus on 4p15 modifying the effect of waist-to-hip ratio on total cholesterol. |
|
| ABSTRACT |
|
|
|
| Recent genome-wide association (GWA) studies described 95 loci controlling serum lipid levels. These common variants explain ∼25% of the heritability of the phenotypes. To date, no unbiased screen for gene-environment interactions for circulating lipids has been reported. We screened for variants that modify the relationship between known epidemiological risk factors and circulating lipid levels in a meta-analysis of genome-wide association (GWA) data from 18 population-based cohorts with European ancestry (maximum N = 32,225). We collected 8 further cohorts (N = 17,102) for replication, and rs6448771 on 4p15 demonstrated genome-wide significant interaction with waist-to-hip-ratio (WHR) on total cholesterol (TC) with a combined P-value of 4.79×10(-9). There were two potential candidate genes in the region, PCDH7 and CCKAR, with differential expression levels for rs6448771 genotypes in adipose tissue. The effect of WHR on TC was strongest for individuals carrying two copies of G allele, for whom a one standard deviation (sd) difference in WHR corresponds to 0.19 sd difference in TC concentration, while for A allele homozygous the difference was 0.12 sd. Our findings may open up possibilities for targeted intervention strategies for people characterized by specific genomic profiles. However, more refined measures of both body-fat distribution and metabolic measures are needed to understand how their joint dynamics are modified by the newly found locus. |
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| DATE PUBLISHED |
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| HISTORY |
|
| PUBSTATUS |
PUBSTATUSDATE |
| received |
2011/06/23 |
| accepted |
2011/08/23 |
| epublish |
2011/10/20 |
| entrez |
2011/10/27 06:00 |
| pubmed |
2011/10/27 06:00 |
| medline |
2012/03/01 06:00 |
|
| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Surakka I |
|
Surakka |
Ida |
I |
|
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. |
| Isaacs A |
|
Isaacs |
Aaron |
A |
|
|
| Karssen LC |
|
Karssen |
Lennart C |
LC |
|
|
| Laurila PP |
|
Laurila |
Pirkka-Pekka P |
PP |
|
|
| Middelberg RP |
|
Middelberg |
Rita P S |
RP |
|
|
| Tikkanen E |
|
Tikkanen |
Emmi |
E |
|
|
| Ried JS |
|
Ried |
Janina S |
JS |
|
|
| Lamina C |
|
Lamina |
Claudia |
C |
|
|
| Mangino M |
|
Mangino |
Massimo |
M |
|
|
| Igl W |
|
Igl |
Wilmar |
W |
|
|
| Hottenga JJ |
|
Hottenga |
Jouke-Jan |
JJ |
|
|
| Lagou V |
|
Lagou |
Vasiliki |
V |
|
|
| van der Harst P |
|
van der Harst |
Pim |
P |
|
|
| Mateo Leach I |
|
Mateo Leach |
Irene |
I |
|
|
| Esko T |
|
Esko |
Tõnu |
T |
|
|
| Kutalik Z |
|
Kutalik |
Zoltán |
Z |
|
|
| Wainwright NW |
|
Wainwright |
Nicholas W |
NW |
|
|
| Struchalin MV |
|
Struchalin |
Maksim V |
MV |
|
|
| Sarin AP |
|
Sarin |
Antti-Pekka |
AP |
|
|
| Kangas AJ |
|
Kangas |
Antti J |
AJ |
|
|
| Viikari JS |
|
Viikari |
Jorma S |
JS |
|
|
| Perola M |
|
Perola |
Markus |
M |
|
|
| Rantanen T |
|
Rantanen |
Taina |
T |
|
|
| Petersen AK |
|
Petersen |
Ann-Kristin |
AK |
|
|
| Soininen P |
|
Soininen |
Pasi |
P |
|
|
| Johansson A |
|
Johansson |
Asa |
A |
|
|
| Soranzo N |
|
Soranzo |
Nicole |
N |
|
|
| Heath AC |
|
Heath |
Andrew C |
AC |
|
|
| Papamarkou T |
|
Papamarkou |
Theodore |
T |
|
|
| Prokopenko I |
|
Prokopenko |
Inga |
I |
|
|
| Tönjes A |
|
Tönjes |
Anke |
A |
|
|
| Kronenberg F |
|
Kronenberg |
Florian |
F |
|
|
| Döring A |
|
Döring |
Angela |
A |
|
|
| Rivadeneira F |
|
Rivadeneira |
Fernando |
F |
|
|
| Montgomery GW |
|
Montgomery |
Grant W |
GW |
|
|
| Whitfield JB |
|
Whitfield |
John B |
JB |
|
|
| Kähönen M |
|
Kähönen |
Mika |
M |
|
|
| Lehtimäki T |
|
Lehtimäki |
Terho |
T |
|
|
| Freimer NB |
|
Freimer |
Nelson B |
NB |
|
|
| Willemsen G |
|
Willemsen |
Gonneke |
G |
|
|
| de Geus EJ |
|
de Geus |
Eco J C |
EJ |
|
|
| Palotie A |
|
Palotie |
Aarno |
A |
|
|
| Sandhu MS |
|
Sandhu |
Manj S |
MS |
|
|
| Waterworth DM |
|
Waterworth |
Dawn M |
DM |
|
|
| Metspalu A |
|
Metspalu |
Andres |
A |
|
|
| Stumvoll M |
|
Stumvoll |
Michael |
M |
|
|
| Uitterlinden AG |
|
Uitterlinden |
André G |
AG |
|
|
| Jula A |
|
Jula |
Antti |
A |
|
|
| Navis G |
|
Navis |
Gerjan |
G |
|
|
| Wijmenga C |
|
Wijmenga |
Cisca |
C |
|
|
| Wolffenbuttel BH |
|
Wolffenbuttel |
Bruce H R |
BH |
|
|
| Taskinen MR |
|
Taskinen |
Marja-Riitta |
MR |
|
|
| Ala-Korpela M |
|
Ala-Korpela |
Mika |
M |
|
|
| Kaprio J |
|
Kaprio |
Jaakko |
J |
|
|
| Kyvik KO |
|
Kyvik |
Kirsten O |
KO |
|
|
| Boomsma DI |
|
Boomsma |
Dorret I |
DI |
|
|
| Pedersen NL |
|
Pedersen |
Nancy L |
NL |
|
|
| Gyllensten U |
|
Gyllensten |
Ulf |
U |
|
|
| Wilson JF |
|
Wilson |
James F |
JF |
|
|
| Rudan I |
|
Rudan |
Igor |
I |
|
|
| Campbell H |
|
Campbell |
Harry |
H |
|
|
| Pramstaller PP |
|
Pramstaller |
Peter P |
PP |
|
|
| Spector TD |
|
Spector |
Tim D |
TD |
|
|
| Witteman JC |
|
Witteman |
Jacqueline C M |
JC |
|
|
| Eriksson JG |
|
Eriksson |
Johan G |
JG |
|
|
| Salomaa V |
|
Salomaa |
Veikko |
V |
|
|
| Oostra BA |
|
Oostra |
Ben A |
BA |
|
|
| Raitakari OT |
|
Raitakari |
Olli T |
OT |
|
|
| Wichmann HE |
|
Wichmann |
H-Erich |
HE |
|
|
| Gieger C |
|
Gieger |
Christian |
C |
|
|
| Järvelin MR |
|
Järvelin |
Marjo-Riitta |
MR |
|
|
| Martin NG |
|
Martin |
Nicholas G |
NG |
|
|
| Hofman A |
|
Hofman |
Albert |
A |
|
|
| McCarthy MI |
|
McCarthy |
Mark I |
MI |
|
|
| Peltonen L |
|
Peltonen |
Leena |
L |
|
|
| van Duijn CM |
|
van Duijn |
Cornelia M |
CM |
|
|
| Aulchenko YS |
|
Aulchenko |
Yurii S |
YS |
|
|
| Ripatti S |
|
Ripatti |
Samuli |
S |
|
|
|
ENGAGE Consortium |
|
|
|
|
|
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| INVESTIGATORS |
|
|
| JOURNAL |
|
| VOLUME: 7 |
| ISSUE: 10 |
| TITLE: PLoS genetics |
| ISOABBREVIATION: PLoS Genet. |
| YEAR: 2011 |
| MONTH: Oct |
| DAY: |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1553-7404 |
| ISSNTYPE: Electronic |
|
| MEDLINE JOURNAL |
|
| MEDLINETA: PLoS Genet |
| COUNTRY: United States |
| ISSNLINKING: 1553-7390 |
| NLMUNIQUEID: 101239074 |
|
| PUBLICATION TYPE |
|
| PUBLICATIONTYPE TEXT |
| Journal Article |
| Research Support, N.I.H., Extramural |
| Research Support, Non-U.S. Gov't |
|
| COMMENTS AND CORRECTIONS |
|
| REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
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|
| GRANTS |
|
| GRANTID |
AGENCY |
COUNTRY |
| 090532 |
Wellcome Trust |
United Kingdom |
| 1R01MH083268-01 |
NIMH NIH HHS |
United States |
| 5R01HL087679 |
NHLBI NIH HHS |
United States |
| AA07535 |
NIAAA NIH HHS |
United States |
| AA10248 |
NIAAA NIH HHS |
United States |
| AA11998 |
NIAAA NIH HHS |
United States |
| AA13320 |
NIAAA NIH HHS |
United States |
| AA13321 |
NIAAA NIH HHS |
United States |
| AA13326 |
NIAAA NIH HHS |
United States |
| AA14041 |
NIAAA NIH HHS |
United States |
| AA17688 |
NIAAA NIH HHS |
United States |
| C865/A2883 |
Cancer Research UK |
United Kingdom |
| CZB/4/710 |
Chief Scientist Office |
United Kingdom |
| DA12854 |
NIDA NIH HHS |
United States |
| G0300128 |
Medical Research Council |
United Kingdom |
| G0801566 |
Medical Research Council |
United Kingdom |
| G9502233 |
Medical Research Council |
United Kingdom |
| K05 AA017688 |
NIAAA NIH HHS |
United States |
| MH66206 |
NIMH NIH HHS |
United States |
| PG/08/094/26019 |
British Heart Foundation |
United Kingdom |
| R01D0042157-01A |
PHS HHS |
United States |
| U24 MH068457-06 |
NIMH NIH HHS |
United States |
| g0500539 |
Medical Research Council |
United Kingdom |
| g600705 |
Medical Research Council |
United Kingdom |
| gr069224 |
Wellcome Trust |
United Kingdom |
|
| GENERAL NOTE |
|
|
| KEYWORDS |
|
|
| MESH HEADINGS |
|
| DESCRIPTORNAME |
QUALIFIERNAME |
| Adipose Tissue |
metabolism |
| Body Fat Distribution |
metabolism |
| Cadherins |
genetics |
| Cholesterol |
genetics |
| Chromosome Mapping |
genetics |
| Chromosomes, Human, Pair 4 |
genetics |
| European Continental Ancestry Group |
genetics |
| Genome-Wide Association Study |
genetics |
| Genotype |
genetics |
| Humans |
genetics |
| Lipids |
genetics |
| Lipoproteins |
genetics |
| Phenotype |
genetics |
| Polymorphism, Single Nucleotide |
genetics |
| Quantitative Trait Loci |
genetics |
| Risk Factors |
genetics |
| Triglycerides |
genetics |
| Waist-Hip Ratio |
genetics |
|
| SUPPLEMENTARY MESH |
|
|
| GENE SYMBOLS |
|
|
| CHEMICALS |
|
| REGISTRYNUMBER |
NAMEOFSUBSTANCE |
| 0 |
Cadherins |
| 0 |
Lipids |
| 0 |
Lipoproteins |
| 0 |
PCDH7 protein, human |
| 0 |
Triglycerides |
| 97C5T2UQ7J |
Cholesterol |
|
| OTHER ID's |
|
| OTHERID |
SOURCE |
| PMC3197672 |
NLM |
|
