Abstract
Rare mutations in more than 20 genes have been suggested to cause dilated cardiomyopathy (DCM), but explain only a small percentage of cases, mainly in familial forms. We hypothesised that more common variants may also play a role in increasing genetic susceptibility to DCM, similar to that observed in other common complex disorders. To test this hypothesis, we performed case-control analyses on all DNA polymorphic variation identified in a resequencing study of six candidate DCM genes (CSRP3, LDB3, MYH7, SCN5A, TCAP, and TNNT2) conducted in 289 unrelated white probands with DCM of unknown cause and 188 unrelated white controls. In univariate analyses, we identified associated common variants at LDB3 site 10779, LDB3 site 57877, MYH7 sites 16384 and 17404, and TCAP sites 140 and 1735. Multivariate analyses to examine the joint effects of multiple gene variants confirmed univariate results for MYH7 and TCAP and identified a block of nine variants in MYH7 that was strongly associated with DCM. Common variants in genes known to be causative of DCM may play a role in genetic susceptibility to DCM. Our results suggest that examination of common genetic variants may be warranted in future studies of DCM and other Mendelian-like disorders.
| Original language | English |
|---|---|
| Pages (from-to) | 110-116 |
| Number of pages | 7 |
| Journal | Annals of Human Genetics |
| Volume | 74 |
| Issue number | 2 |
| DOIs | |
| State | Published - Mar 1 2010 |
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Keywords
- Dilated cardiomyopathy
- Genetics
- Multivariate analyses
- Resequencing
ASJC Scopus subject areas
- Genetics(clinical)
- Genetics
Cite this
Common susceptibility variants Examined for association with dilated cardiomyopathy. / Rampersaud, Evadnie; Kinnamon, Daniel D.; Hamilton, Kara; Khuri, Sawsan; Hershberger, Ray E.; Martin, Eden R.
In: Annals of Human Genetics, Vol. 74, No. 2, 01.03.2010, p. 110-116.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Common susceptibility variants Examined for association with dilated cardiomyopathy
AU - Rampersaud, Evadnie
AU - Kinnamon, Daniel D.
AU - Hamilton, Kara
AU - Khuri, Sawsan
AU - Hershberger, Ray E.
AU - Martin, Eden R
PY - 2010/3/1
Y1 - 2010/3/1
N2 - Rare mutations in more than 20 genes have been suggested to cause dilated cardiomyopathy (DCM), but explain only a small percentage of cases, mainly in familial forms. We hypothesised that more common variants may also play a role in increasing genetic susceptibility to DCM, similar to that observed in other common complex disorders. To test this hypothesis, we performed case-control analyses on all DNA polymorphic variation identified in a resequencing study of six candidate DCM genes (CSRP3, LDB3, MYH7, SCN5A, TCAP, and TNNT2) conducted in 289 unrelated white probands with DCM of unknown cause and 188 unrelated white controls. In univariate analyses, we identified associated common variants at LDB3 site 10779, LDB3 site 57877, MYH7 sites 16384 and 17404, and TCAP sites 140 and 1735. Multivariate analyses to examine the joint effects of multiple gene variants confirmed univariate results for MYH7 and TCAP and identified a block of nine variants in MYH7 that was strongly associated with DCM. Common variants in genes known to be causative of DCM may play a role in genetic susceptibility to DCM. Our results suggest that examination of common genetic variants may be warranted in future studies of DCM and other Mendelian-like disorders.
AB - Rare mutations in more than 20 genes have been suggested to cause dilated cardiomyopathy (DCM), but explain only a small percentage of cases, mainly in familial forms. We hypothesised that more common variants may also play a role in increasing genetic susceptibility to DCM, similar to that observed in other common complex disorders. To test this hypothesis, we performed case-control analyses on all DNA polymorphic variation identified in a resequencing study of six candidate DCM genes (CSRP3, LDB3, MYH7, SCN5A, TCAP, and TNNT2) conducted in 289 unrelated white probands with DCM of unknown cause and 188 unrelated white controls. In univariate analyses, we identified associated common variants at LDB3 site 10779, LDB3 site 57877, MYH7 sites 16384 and 17404, and TCAP sites 140 and 1735. Multivariate analyses to examine the joint effects of multiple gene variants confirmed univariate results for MYH7 and TCAP and identified a block of nine variants in MYH7 that was strongly associated with DCM. Common variants in genes known to be causative of DCM may play a role in genetic susceptibility to DCM. Our results suggest that examination of common genetic variants may be warranted in future studies of DCM and other Mendelian-like disorders.
KW - Dilated cardiomyopathy
KW - Genetics
KW - Multivariate analyses
KW - Resequencing
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U2 - 10.1111/j.1469-1809.2010.00566.x
DO - 10.1111/j.1469-1809.2010.00566.x
M3 - Article
C2 - 20201937
AN - SCOPUS:77951915607
VL - 74
SP - 110
EP - 116
JO - Annals of Human Genetics
JF - Annals of Human Genetics
SN - 0003-4800
IS - 2
ER -