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PMID |
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TITLE |
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Biological, clinical and population relevance of 95 loci for blood lipids. |
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ABSTRACT |
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Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD. |
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DATE PUBLISHED |
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HISTORY |
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PUBSTATUS |
PUBSTATUSDATE |
received |
2010/02/25 |
accepted |
2010/06/11 |
entrez |
2010/08/06 06:00 |
pubmed |
2010/08/06 06:00 |
medline |
2010/09/25 06:00 |
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AUTHORS |
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NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
Teslovich TM |
|
Teslovich |
Tanya M |
TM |
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Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA. |
Musunuru K |
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Musunuru |
Kiran |
K |
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Smith AV |
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Smith |
Albert V |
AV |
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Edmondson AC |
|
Edmondson |
Andrew C |
AC |
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Stylianou IM |
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Stylianou |
Ioannis M |
IM |
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Koseki M |
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Koseki |
Masahiro |
M |
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Pirruccello JP |
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Pirruccello |
James P |
JP |
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Ripatti S |
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Ripatti |
Samuli |
S |
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Chasman DI |
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Chasman |
Daniel I |
DI |
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Willer CJ |
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Willer |
Cristen J |
CJ |
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Johansen CT |
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Johansen |
Christopher T |
CT |
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Fouchier SW |
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Fouchier |
Sigrid W |
SW |
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Isaacs A |
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Isaacs |
Aaron |
A |
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Peloso GM |
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Peloso |
Gina M |
GM |
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Barbalic M |
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Barbalic |
Maja |
M |
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Ricketts SL |
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Ricketts |
Sally L |
SL |
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Bis JC |
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Bis |
Joshua C |
JC |
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Aulchenko YS |
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Aulchenko |
Yurii S |
YS |
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Thorleifsson G |
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Thorleifsson |
Gudmar |
G |
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Feitosa MF |
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Feitosa |
Mary F |
MF |
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Chambers J |
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Chambers |
John |
J |
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Orho-Melander M |
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Orho-Melander |
Marju |
M |
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Melander O |
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Melander |
Olle |
O |
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Johnson T |
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Johnson |
Toby |
T |
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Li X |
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Li |
Xiaohui |
X |
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Guo X |
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Guo |
Xiuqing |
X |
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Li M |
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Li |
Mingyao |
M |
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Shin Cho Y |
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Shin Cho |
Yoon |
Y |
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Jin Go M |
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Jin Go |
Min |
M |
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Jin Kim Y |
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Jin Kim |
Young |
Y |
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Lee JY |
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Lee |
Jong-Young |
JY |
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Park T |
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Park |
Taesung |
T |
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Kim K |
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Kim |
Kyunga |
K |
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Sim X |
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Sim |
Xueling |
X |
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Twee-Hee Ong R |
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Twee-Hee Ong |
Rick |
R |
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Croteau-Chonka DC |
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Croteau-Chonka |
Damien C |
DC |
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Lange LA |
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Lange |
Leslie A |
LA |
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Smith JD |
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Smith |
Joshua D |
JD |
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Song K |
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Song |
Kijoung |
K |
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Hua Zhao J |
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Hua Zhao |
Jing |
J |
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Yuan X |
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Yuan |
Xin |
X |
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Luan J |
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Luan |
Jian'an |
J |
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Lamina C |
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Lamina |
Claudia |
C |
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Ziegler A |
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Ziegler |
Andreas |
A |
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Zhang W |
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Zhang |
Weihua |
W |
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Zee RY |
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Zee |
Robert Y L |
RY |
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Wright AF |
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Wright |
Alan F |
AF |
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Witteman JC |
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Witteman |
Jacqueline C M |
JC |
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Wilson JF |
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Wilson |
James F |
JF |
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Willemsen G |
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Willemsen |
Gonneke |
G |
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Wichmann HE |
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Wichmann |
H-Erich |
HE |
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Whitfield JB |
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Whitfield |
John B |
JB |
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Waterworth DM |
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Waterworth |
Dawn M |
DM |
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Wareham NJ |
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Wareham |
Nicholas J |
NJ |
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Waeber G |
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Waeber |
Gérard |
G |
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Vollenweider P |
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Vollenweider |
Peter |
P |
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Voight BF |
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Voight |
Benjamin F |
BF |
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Vitart V |
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Vitart |
Veronique |
V |
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Uitterlinden AG |
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Uitterlinden |
Andre G |
AG |
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Uda M |
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Uda |
Manuela |
M |
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Tuomilehto J |
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Tuomilehto |
Jaakko |
J |
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Thompson JR |
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Thompson |
John R |
JR |
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Tanaka T |
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Tanaka |
Toshiko |
T |
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Surakka I |
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Surakka |
Ida |
I |
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Stringham HM |
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Stringham |
Heather M |
HM |
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Spector TD |
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Spector |
Tim D |
TD |
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Soranzo N |
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Soranzo |
Nicole |
N |
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Smit JH |
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Smit |
Johannes H |
JH |
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Sinisalo J |
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Sinisalo |
Juha |
J |
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Silander K |
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Silander |
Kaisa |
K |
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Sijbrands EJ |
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Sijbrands |
Eric J G |
EJ |
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Scuteri A |
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Scuteri |
Angelo |
A |
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Scott J |
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Scott |
James |
J |
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Schlessinger D |
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Schlessinger |
David |
D |
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Sanna S |
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Sanna |
Serena |
S |
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Salomaa V |
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Salomaa |
Veikko |
V |
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Saharinen J |
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Saharinen |
Juha |
J |
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Sabatti C |
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Sabatti |
Chiara |
C |
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Ruokonen A |
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Ruokonen |
Aimo |
A |
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Rudan I |
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Rudan |
Igor |
I |
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Rose LM |
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Rose |
Lynda M |
LM |
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Roberts R |
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Roberts |
Robert |
R |
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Rieder M |
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Rieder |
Mark |
M |
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Psaty BM |
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Psaty |
Bruce M |
BM |
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Pramstaller PP |
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Pramstaller |
Peter P |
PP |
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Pichler I |
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Pichler |
Irene |
I |
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Perola M |
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Perola |
Markus |
M |
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Penninx BW |
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Penninx |
Brenda W J H |
BW |
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Pedersen NL |
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Pedersen |
Nancy L |
NL |
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Pattaro C |
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Pattaro |
Cristian |
C |
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Parker AN |
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Parker |
Alex N |
AN |
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Pare G |
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Pare |
Guillaume |
G |
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Oostra BA |
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Oostra |
Ben A |
BA |
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O'Donnell CJ |
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O'Donnell |
Christopher J |
CJ |
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Nieminen MS |
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Nieminen |
Markku S |
MS |
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Nickerson DA |
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Nickerson |
Deborah A |
DA |
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Montgomery GW |
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Montgomery |
Grant W |
GW |
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Meitinger T |
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Meitinger |
Thomas |
T |
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McPherson R |
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McPherson |
Ruth |
R |
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McCarthy MI |
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McCarthy |
Mark I |
MI |
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McArdle W |
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McArdle |
Wendy |
W |
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Masson D |
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Masson |
David |
D |
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Martin NG |
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Martin |
Nicholas G |
NG |
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Marroni F |
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Marroni |
Fabio |
F |
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Mangino M |
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Mangino |
Massimo |
M |
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Magnusson PK |
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Magnusson |
Patrik K E |
PK |
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Lucas G |
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Lucas |
Gavin |
G |
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Luben R |
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Luben |
Robert |
R |
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Loos RJ |
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Loos |
Ruth J F |
RJ |
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Lokki ML |
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Lokki |
Marja-Liisa |
ML |
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Lettre G |
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Lettre |
Guillaume |
G |
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Langenberg C |
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Langenberg |
Claudia |
C |
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Launer LJ |
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Launer |
Lenore J |
LJ |
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Lakatta EG |
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Lakatta |
Edward G |
EG |
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Laaksonen R |
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Laaksonen |
Reijo |
R |
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Kyvik KO |
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Kyvik |
Kirsten O |
KO |
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Kronenberg F |
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Kronenberg |
Florian |
F |
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König IR |
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König |
Inke R |
IR |
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Khaw KT |
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Khaw |
Kay-Tee |
KT |
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Kaprio J |
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Kaprio |
Jaakko |
J |
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Kaplan LM |
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Kaplan |
Lee M |
LM |
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Johansson A |
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Johansson |
Asa |
A |
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Jarvelin MR |
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Jarvelin |
Marjo-Riitta |
MR |
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Janssens AC |
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Janssens |
A Cecile J W |
AC |
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Ingelsson E |
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Ingelsson |
Erik |
E |
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Igl W |
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Igl |
Wilmar |
W |
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Kees Hovingh G |
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Kees Hovingh |
G |
G |
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Hottenga JJ |
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Hottenga |
Jouke-Jan |
JJ |
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Hofman A |
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Hofman |
Albert |
A |
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Hicks AA |
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Hicks |
Andrew A |
AA |
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Hengstenberg C |
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Hengstenberg |
Christian |
C |
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Heid IM |
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Heid |
Iris M |
IM |
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Hayward C |
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Hayward |
Caroline |
C |
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Havulinna AS |
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Havulinna |
Aki S |
AS |
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Hastie ND |
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Hastie |
Nicholas D |
ND |
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Harris TB |
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Harris |
Tamara B |
TB |
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Haritunians T |
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Haritunians |
Talin |
T |
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Hall AS |
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Hall |
Alistair S |
AS |
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Gyllensten U |
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Gyllensten |
Ulf |
U |
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Guiducci C |
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Guiducci |
Candace |
C |
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Groop LC |
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Groop |
Leif C |
LC |
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Gonzalez E |
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Gonzalez |
Elena |
E |
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Gieger C |
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Gieger |
Christian |
C |
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Freimer NB |
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Freimer |
Nelson B |
NB |
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Ferrucci L |
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Ferrucci |
Luigi |
L |
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Erdmann J |
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Erdmann |
Jeanette |
J |
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Elliott P |
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Elliott |
Paul |
P |
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Ejebe KG |
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Ejebe |
Kenechi G |
KG |
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Döring A |
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Döring |
Angela |
A |
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Dominiczak AF |
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Dominiczak |
Anna F |
AF |
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Demissie S |
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Demissie |
Serkalem |
S |
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Deloukas P |
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Deloukas |
Panagiotis |
P |
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de Geus EJ |
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de Geus |
Eco J C |
EJ |
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de Faire U |
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de Faire |
Ulf |
U |
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Crawford G |
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Crawford |
Gabriel |
G |
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Collins FS |
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Collins |
Francis S |
FS |
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Chen YD |
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Chen |
Yii-der I |
YD |
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Caulfield MJ |
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Caulfield |
Mark J |
MJ |
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Campbell H |
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Campbell |
Harry |
H |
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Burtt NP |
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Burtt |
Noel P |
NP |
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Bonnycastle LL |
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Bonnycastle |
Lori L |
LL |
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Boomsma DI |
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Boomsma |
Dorret I |
DI |
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Boekholdt SM |
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Boekholdt |
S Matthijs |
SM |
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Bergman RN |
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Bergman |
Richard N |
RN |
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Barroso I |
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Barroso |
Inês |
I |
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Bandinelli S |
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Bandinelli |
Stefania |
S |
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Ballantyne CM |
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Ballantyne |
Christie M |
CM |
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Assimes TL |
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Assimes |
Themistocles L |
TL |
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Quertermous T |
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Quertermous |
Thomas |
T |
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Altshuler D |
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Altshuler |
David |
D |
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Seielstad M |
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Seielstad |
Mark |
M |
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Wong TY |
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Wong |
Tien Y |
TY |
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Tai ES |
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Tai |
E-Shyong |
ES |
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Feranil AB |
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Feranil |
Alan B |
AB |
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Kuzawa CW |
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Kuzawa |
Christopher W |
CW |
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Adair LS |
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Adair |
Linda S |
LS |
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Taylor HA Jr |
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Taylor |
Herman A |
HA |
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Borecki IB |
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Borecki |
Ingrid B |
IB |
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Gabriel SB |
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Gabriel |
Stacey B |
SB |
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Wilson JG |
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Wilson |
James G |
JG |
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Holm H |
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Holm |
Hilma |
H |
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Thorsteinsdottir U |
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Thorsteinsdottir |
Unnur |
U |
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Gudnason V |
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Gudnason |
Vilmundur |
V |
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Krauss RM |
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Krauss |
Ronald M |
RM |
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Mohlke KL |
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Mohlke |
Karen L |
KL |
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Ordovas JM |
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Ordovas |
Jose M |
JM |
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Munroe PB |
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Munroe |
Patricia B |
PB |
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Kooner JS |
|
Kooner |
Jaspal S |
JS |
|
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Tall AR |
|
Tall |
Alan R |
AR |
|
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Hegele RA |
|
Hegele |
Robert A |
RA |
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Kastelein JJ |
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Kastelein |
John J P |
JJ |
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Schadt EE |
|
Schadt |
Eric E |
EE |
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Rotter JI |
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Rotter |
Jerome I |
JI |
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Boerwinkle E |
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Boerwinkle |
Eric |
E |
|
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Strachan DP |
|
Strachan |
David P |
DP |
|
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Mooser V |
|
Mooser |
Vincent |
V |
|
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Stefansson K |
|
Stefansson |
Kari |
K |
|
|
Reilly MP |
|
Reilly |
Muredach P |
MP |
|
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Samani NJ |
|
Samani |
Nilesh J |
NJ |
|
|
Schunkert H |
|
Schunkert |
Heribert |
H |
|
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Cupples LA |
|
Cupples |
L Adrienne |
LA |
|
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Sandhu MS |
|
Sandhu |
Manjinder S |
MS |
|
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Ridker PM |
|
Ridker |
Paul M |
PM |
|
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Rader DJ |
|
Rader |
Daniel J |
DJ |
|
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van Duijn CM |
|
van Duijn |
Cornelia M |
CM |
|
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Peltonen L |
|
Peltonen |
Leena |
L |
|
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Abecasis GR |
|
Abecasis |
Gonçalo R |
GR |
|
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Boehnke M |
|
Boehnke |
Michael |
M |
|
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Kathiresan S |
|
Kathiresan |
Sekar |
S |
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INVESTIGATORS |
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JOURNAL |
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VOLUME: 466 |
ISSUE: 7307 |
TITLE: Nature |
ISOABBREVIATION: Nature |
YEAR: 2010 |
MONTH: Aug |
DAY: 5 |
MEDLINEDATE: |
SEASON: |
CITEDMEDIUM: Internet |
ISSN: 1476-4687 |
ISSNTYPE: Electronic |
|
MEDLINE JOURNAL |
|
MEDLINETA: Nature |
COUNTRY: England |
ISSNLINKING: 0028-0836 |
NLMUNIQUEID: 0410462 |
|
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 |
|
COMMENTS AND CORRECTIONS |
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REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
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GRANTS |
|
GRANTID |
AGENCY |
COUNTRY |
068545/Z/02 |
Wellcome Trust |
United Kingdom |
076113/B/04/Z |
Wellcome Trust |
United Kingdom |
077016/Z/05/Z |
Wellcome Trust |
United Kingdom |
079895 |
Wellcome Trust |
United Kingdom |
1Z01 HG000024 |
NHGRI NIH HHS |
United States |
5R01DK06833603 |
NIDDK NIH HHS |
United States |
5R01DK07568102 |
NIDDK NIH HHS |
United States |
5R01HL087679-02 |
NHLBI NIH HHS |
United States |
5R01HL08770003 |
NHLBI NIH HHS |
United States |
5R01HL08821502 |
NHLBI NIH HHS |
United States |
CA 047988 |
NCI NIH HHS |
United States |
CZB/4/710 |
Chief Scientist Office |
United Kingdom |
DK062370 |
NIDDK NIH HHS |
United States |
DK063491 |
NIDDK NIH HHS |
United States |
DK072193 |
NIDDK NIH HHS |
United States |
DK078150 |
NIDDK NIH HHS |
United States |
DK56350 |
NIDDK NIH HHS |
United States |
ES10126 |
NIEHS NIH HHS |
United States |
G0000934 |
Medical Research Council |
United Kingdom |
G0401527 |
Medical Research Council |
United Kingdom |
G0601966 |
Medical Research Council |
United Kingdom |
G0700931 |
Medical Research Council |
United Kingdom |
G0701863 |
Medical Research Council |
United Kingdom |
G0801056 |
Medical Research Council |
United Kingdom |
G0801566 |
Medical Research Council |
United Kingdom |
G9521010 |
Medical Research Council |
United Kingdom |
G9521010D |
Medical Research Council |
United Kingdom |
HHSN268200625226C |
PHS HHS |
United States |
HL 04381 |
NHLBI NIH HHS |
United States |
HL 080467 |
NHLBI NIH HHS |
United States |
HL-54776 |
NHLBI NIH HHS |
United States |
HL085144 |
NHLBI NIH HHS |
United States |
K99 HL098364 |
NHLBI NIH HHS |
United States |
K99 HL098364 |
NHLBI NIH HHS |
United States |
K99 HL098364-01 |
NHLBI NIH HHS |
United States |
K99HL094535 |
NHLBI NIH HHS |
United States |
M01-RR00425 |
NCRR NIH HHS |
United States |
MC_QA137934 |
Medical Research Council |
United Kingdom |
MC_U106179471 |
Medical Research Council |
United Kingdom |
MC_U106188470 |
Medical Research Council |
United Kingdom |
MC_U127561128 |
Medical Research Council |
United Kingdom |
N01 HC-15103 |
NHLBI NIH HHS |
United States |
N01 HC-55222 |
NHLBI NIH HHS |
United States |
N01-AG-12100 |
NIA NIH HHS |
United States |
N01-HC-25195 |
NHLBI NIH HHS |
United States |
N01-HC-35129 |
NHLBI NIH HHS |
United States |
N01-HC-45133 |
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-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-HG-65403 |
NHGRI NIH HHS |
United States |
N02-HL-6-4278 |
NHLBI NIH HHS |
United States |
PG/02/128 |
British Heart Foundation |
United Kingdom |
PG/08/094 |
British Heart Foundation |
United Kingdom |
PG/08/094/26019 |
British Heart Foundation |
United Kingdom |
R01 DK072193 |
NIDDK NIH HHS |
United States |
R01 DK078150 |
NIDDK NIH HHS |
United States |
R01 HL087647 |
NHLBI NIH HHS |
United States |
R01 HL087676 |
NHLBI NIH HHS |
United States |
R01 HL089650 |
NHLBI NIH HHS |
United States |
R01HL086694 |
NHLBI NIH HHS |
United States |
R01HL087641 |
NHLBI NIH HHS |
United States |
R01HL087652 |
NHLBI NIH HHS |
United States |
R01HL59367 |
NHLBI NIH HHS |
United States |
R24 HD050924 |
NICHD NIH HHS |
United States |
RC1 HL099634 |
NHLBI NIH HHS |
United States |
RC1 HL099634 |
NHLBI NIH HHS |
United States |
RC1 HL099634-02 |
NHLBI NIH HHS |
United States |
RC1 HL099793 |
NHLBI NIH HHS |
United States |
RC2 HL101864, |
NHLBI NIH HHS |
United States |
RC2 HL102419 |
NHLBI NIH HHS |
United States |
RG/07/005/23633 |
British Heart Foundation |
United Kingdom |
RR20649 |
NCRR NIH HHS |
United States |
SP/08/005/25115 |
British Heart Foundation |
United Kingdom |
T32 GM007092 |
NIGMS NIH HHS |
United States |
T32 HG00040 |
NHGRI NIH HHS |
United States |
T32HL007208 |
NHLBI NIH HHS |
United States |
TW05596 |
FIC NIH HHS |
United States |
U01 DK062370 |
NIDDK NIH HHS |
United States |
U01 DK062418 |
NIDDK NIH HHS |
United States |
U01 HL069757 |
NHLBI NIH HHS |
United States |
U01 HL080295 |
NHLBI NIH HHS |
United States |
U01HG004402 |
NHGRI NIH HHS |
United States |
U54 RR020278 |
NCRR NIH HHS |
United States |
UL1RR025005 |
NCRR NIH HHS |
United States |
|
Intramural NIH HHS |
United States |
|
GENERAL NOTE |
|
|
KEYWORDS |
|
|
MESH HEADINGS |
|
DESCRIPTORNAME |
QUALIFIERNAME |
African Americans |
genetics |
Animals |
genetics |
Asian Continental Ancestry Group |
genetics |
Cholesterol, HDL |
blood |
Cholesterol, LDL |
blood |
Coronary Artery Disease |
therapy |
Europe |
ethnology |
European Continental Ancestry Group |
genetics |
Female |
genetics |
Genetic Loci |
genetics |
Genome-Wide Association Study |
genetics |
Genotype |
genetics |
Humans |
genetics |
Lipid Metabolism |
genetics |
Lipids |
blood |
Liver |
metabolism |
Male |
metabolism |
Mice |
metabolism |
N-Acetylgalactosaminyltransferases |
metabolism |
Phenotype |
metabolism |
Polymorphism, Single Nucleotide |
genetics |
Protein Phosphatase 1 |
metabolism |
Reproducibility of Results |
metabolism |
Triglycerides |
blood |
|
SUPPLEMENTARY MESH |
|
|
GENE SYMBOLS |
|
|
CHEMICALS |
|
REGISTRYNUMBER |
NAMEOFSUBSTANCE |
0 |
Cholesterol, HDL |
0 |
Cholesterol, LDL |
0 |
Lipids |
0 |
Triglycerides |
EC 2.4.1.- |
N-Acetylgalactosaminyltransferases |
EC 2.4.1.41 |
polypeptide N-acetylgalactosaminyltransferase |
EC 3.1.3.16 |
Ppp1r3b protein, mouse |
EC 3.1.3.16 |
Protein Phosphatase 1 |
|
OTHER ID's |
|
OTHERID |
SOURCE |
NIHMS213289 |
NLM |
PMC3039276 |
NLM |
|
|