PMID- 20150558
OWN - NLM
STAT- MEDLINE
DCOM- 20100416
LR  - 20211020
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Print)
IS  - 1079-5642 (Linking)
VI  - 30
IP  - 4
DP  - 2010 Apr
TI  - Genome-wide association study identifies variants at the IL18-BCO2 locus 
      associated with interleukin-18 levels.
PG  - 885-90
LID - 10.1161/ATVBAHA.109.199422 [doi]
AB  - OBJECTIVE: Interleukin-18 (IL-18) is a proinflammatory cytokine involved in the 
      processes of innate and acquired immunities and associated with cardiovascular 
      disease and type 2 diabetes. We sought to identify the common genetic variants 
      associated with IL-18 levels. METHODS AND RESULTS: We performed a 2-stage 
      genome-wide association study among women of European ancestry from the Nurses' 
      Health Study (NHS) and Women's Genome Health Study (WGHS). IL-18 levels were 
      measured by ELISA. In the discovery stage (NHS, n=1523), 7 single-nucleotide 
      polymorphisms (SNPs) at the IL18-BCO2 locus were associated with IL-18 
      concentrations at the 1 x 10(-5) significance level. The strongest association 
      was found for SNP rs2115763 in the BCO2 gene (P=6.31 x 10(-8)). In silico 
      replication in WGHS (435 women) confirmed these findings. The combined analysis 
      of the 2 studies indicated that SNPs rs2115763, rs1834481, and rs7106524 reached 
      a genome-wide significance level (P<5 x 10(-8)). Forward selection analysis 
      indicated that SNPs rs2115763 and rs1834481 were independently associated with 
      IL-18 levels (P=0.0002 and 0.0006, respectively). The 2 SNPs together explained 
      2.9% of variation of plasma IL-18 levels. CONCLUSIONS: This study identified 
      several novel variants at the IL18-BCO2 locus associated with IL-18 levels.
FAU - He, Meian
AU  - He M
AD  - Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA.
FAU - Cornelis, Marilyn C
AU  - Cornelis MC
FAU - Kraft, Peter
AU  - Kraft P
FAU - van Dam, Rob M
AU  - van Dam RM
FAU - Sun, Qi
AU  - Sun Q
FAU - Laurie, Cathy C
AU  - Laurie CC
FAU - Mirel, Daniel B
AU  - Mirel DB
FAU - Chasman, Daniel I
AU  - Chasman DI
FAU - Ridker, Paul M
AU  - Ridker PM
FAU - Hunter, David J
AU  - Hunter DJ
FAU - Hu, Frank B
AU  - Hu FB
FAU - Qi, Lu
AU  - Qi L
LA  - eng
GR  - U01 HG004446/HG/NHGRI NIH HHS/United States
GR  - P01 CA087969/CA/NCI NIH HHS/United States
GR  - U01 DE018993/DE/NIDCR NIH HHS/United States
GR  - R01-DK058845/DK/NIDDK NIH HHS/United States
GR  - U01 HG004415/HG/NHGRI NIH HHS/United States
GR  - HHSN268200782096C/HG/NHGRI NIH HHS/United States
GR  - U01 HG004422/HG/NHGRI NIH HHS/United States
GR  - R01 HL071981/HL/NHLBI NIH HHS/United States
GR  - U01 HG004735/HG/NHGRI NIH HHS/United States
GR  - U01 HG004738/HG/NHGRI NIH HHS/United States
GR  - P01-CA055075/CA/NCI NIH HHS/United States
GR  - U01 HG004399/HG/NHGRI NIH HHS/United States
GR  - DK46200/DK/NIDDK NIH HHS/United States
GR  - U01 HG004726/HG/NHGRI NIH HHS/United States
GR  - P01-CA087969/CA/NCI NIH HHS/United States
GR  - R01 DK058845/DK/NIDDK NIH HHS/United States
GR  - U01 HG004728/HG/NHGRI NIH HHS/United States
GR  - U01 HG004438/HG/NHGRI NIH HHS/United States
GR  - P01 CA055075/CA/NCI NIH HHS/United States
GR  - R01 HL071981-05A1/HL/NHLBI NIH HHS/United States
GR  - U01 HG004402/HG/NHGRI NIH HHS/United States
GR  - U01 HG004424/HG/NHGRI NIH HHS/United States
GR  - P30 DK046200/DK/NIDDK NIH HHS/United States
GR  - U01 HG004729/HG/NHGRI NIH HHS/United States
GR  - U01 DE018903/DE/NIDCR NIH HHS/United States
GR  - U01 HG004436/HG/NHGRI NIH HHS/United States
GR  - R01-HL71981/HL/NHLBI NIH HHS/United States
GR  - U01 HG004423/HG/NHGRI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100211
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Biomarkers)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-18)
SB  - IM
MH  - Biomarkers/blood
MH  - Case-Control Studies
MH  - Diabetes Mellitus, Type 2/*genetics/*immunology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Gene Frequency
MH  - Genome-Wide Association Study
MH  - Genotype
MH  - Humans
MH  - Inflammation Mediators/*blood
MH  - Interleukin-18/*blood/*genetics
MH  - Linear Models
MH  - Linkage Disequilibrium
MH  - Middle Aged
MH  - Phenotype
MH  - *Polymorphism, Single Nucleotide
PMC - PMC2841960
MID - NIHMS181038
EDAT- 2010/02/13 06:00
MHDA- 2010/04/17 06:00
PMCR- 2011/04/01
CRDT- 2010/02/13 06:00
PHST- 2010/02/13 06:00 [entrez]
PHST- 2010/02/13 06:00 [pubmed]
PHST- 2010/04/17 06:00 [medline]
PHST- 2011/04/01 00:00 [pmc-release]
AID - ATVBAHA.109.199422 [pii]
AID - 10.1161/ATVBAHA.109.199422 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2010 Apr;30(4):885-90. doi: 
      10.1161/ATVBAHA.109.199422. Epub 2010 Feb 11.