Abstract
The CATHGEN study reported associations of chromosome 3q13-21 genes (KALRN, MYLK, CDGAP, and GATA2) with early-onset coronary artery disease (CAD). This study attempted to independently validate those associations. Eleven single nucleotide polymorphisms (SNPs) were examined (rs10934490, rs16834817, rs6810298, rs9289231, rs12637456, rs1444768, rs1444754, rs4234218, rs2335052, rs3803, rs2713604) in patients (N = 1618) from the Intermountain Heart Collaborative Study (IHCS). Given the higher smoking prevalence in CATHGEN than IHCS (41% vs. 11% in controls, 74% vs. 29% in cases), smoking stratification and genotype-smoking interactions were evaluated. Suggestive association was found for GATA2 (rs2713604, p = 0.057, OR = 1.2). Among smokers, associations were found in CDGAP (rs10934490, p = 0.019, OR = 1.6) and KALRN (rs12637456, p = 0.011, OR = 2.0) and suggestive association was found in MYLK (rs16834871, p = 0.051, OR = 1.8, adjusting for gender). No SNP association was found among non-smokers, but smoking/SNP interactions were detected for CDGAP (rs10934491, p = 0.017) and KALRN (rs12637456, p = 0.010). Similar differences in SNP effects by smoking status were observed on re-analysis of CATHGEN. CAD associations were suggestive for GATA2 and among smokers significant post hoc associations were found in KALRN, MYLK, and CDGAP. Genetic risk conferred by some of these genes may be modified by smoking. Future CAD association studies of these and other genes should evaluate effect modification by smoking.
| Original language | English |
|---|---|
| Pages (from-to) | 551-558 |
| Number of pages | 8 |
| Journal | Annals of Human Genetics |
| Volume | 73 |
| Issue number | 6 |
| DOIs | |
| State | Published - Nov 1 2009 |
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Keywords
- Coronary disease
- Genetic association
- Replication study
- Smoking
ASJC Scopus subject areas
- Genetics(clinical)
- Genetics
Cite this
Validation study of genetic associations with coronary artery disease on chromosome 3q13-21 and potential effect modification by smoking. / Horne, Benjamin D.; Hauser, Elizabeth R.; Wang, Liyong; Muhlestein, Joseph B.; Anderson, Jeffrey L.; Carlquist, John F.; Shah, Svati H.; Kraus, William E.
In: Annals of Human Genetics, Vol. 73, No. 6, 01.11.2009, p. 551-558.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Validation study of genetic associations with coronary artery disease on chromosome 3q13-21 and potential effect modification by smoking
AU - Horne, Benjamin D.
AU - Hauser, Elizabeth R.
AU - Wang, Liyong
AU - Muhlestein, Joseph B.
AU - Anderson, Jeffrey L.
AU - Carlquist, John F.
AU - Shah, Svati H.
AU - Kraus, William E.
PY - 2009/11/1
Y1 - 2009/11/1
N2 - The CATHGEN study reported associations of chromosome 3q13-21 genes (KALRN, MYLK, CDGAP, and GATA2) with early-onset coronary artery disease (CAD). This study attempted to independently validate those associations. Eleven single nucleotide polymorphisms (SNPs) were examined (rs10934490, rs16834817, rs6810298, rs9289231, rs12637456, rs1444768, rs1444754, rs4234218, rs2335052, rs3803, rs2713604) in patients (N = 1618) from the Intermountain Heart Collaborative Study (IHCS). Given the higher smoking prevalence in CATHGEN than IHCS (41% vs. 11% in controls, 74% vs. 29% in cases), smoking stratification and genotype-smoking interactions were evaluated. Suggestive association was found for GATA2 (rs2713604, p = 0.057, OR = 1.2). Among smokers, associations were found in CDGAP (rs10934490, p = 0.019, OR = 1.6) and KALRN (rs12637456, p = 0.011, OR = 2.0) and suggestive association was found in MYLK (rs16834871, p = 0.051, OR = 1.8, adjusting for gender). No SNP association was found among non-smokers, but smoking/SNP interactions were detected for CDGAP (rs10934491, p = 0.017) and KALRN (rs12637456, p = 0.010). Similar differences in SNP effects by smoking status were observed on re-analysis of CATHGEN. CAD associations were suggestive for GATA2 and among smokers significant post hoc associations were found in KALRN, MYLK, and CDGAP. Genetic risk conferred by some of these genes may be modified by smoking. Future CAD association studies of these and other genes should evaluate effect modification by smoking.
AB - The CATHGEN study reported associations of chromosome 3q13-21 genes (KALRN, MYLK, CDGAP, and GATA2) with early-onset coronary artery disease (CAD). This study attempted to independently validate those associations. Eleven single nucleotide polymorphisms (SNPs) were examined (rs10934490, rs16834817, rs6810298, rs9289231, rs12637456, rs1444768, rs1444754, rs4234218, rs2335052, rs3803, rs2713604) in patients (N = 1618) from the Intermountain Heart Collaborative Study (IHCS). Given the higher smoking prevalence in CATHGEN than IHCS (41% vs. 11% in controls, 74% vs. 29% in cases), smoking stratification and genotype-smoking interactions were evaluated. Suggestive association was found for GATA2 (rs2713604, p = 0.057, OR = 1.2). Among smokers, associations were found in CDGAP (rs10934490, p = 0.019, OR = 1.6) and KALRN (rs12637456, p = 0.011, OR = 2.0) and suggestive association was found in MYLK (rs16834871, p = 0.051, OR = 1.8, adjusting for gender). No SNP association was found among non-smokers, but smoking/SNP interactions were detected for CDGAP (rs10934491, p = 0.017) and KALRN (rs12637456, p = 0.010). Similar differences in SNP effects by smoking status were observed on re-analysis of CATHGEN. CAD associations were suggestive for GATA2 and among smokers significant post hoc associations were found in KALRN, MYLK, and CDGAP. Genetic risk conferred by some of these genes may be modified by smoking. Future CAD association studies of these and other genes should evaluate effect modification by smoking.
KW - Coronary disease
KW - Genetic association
KW - Replication study
KW - Smoking
UR - http://www.scopus.com/inward/record.url?scp=70350537083&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70350537083&partnerID=8YFLogxK
U2 - 10.1111/j.1469-1809.2009.00540.x
DO - 10.1111/j.1469-1809.2009.00540.x
M3 - Article
C2 - 19706030
AN - SCOPUS:70350537083
VL - 73
SP - 551
EP - 558
JO - Annals of Human Genetics
JF - Annals of Human Genetics
SN - 0003-4800
IS - 6
ER -