Meta analysis of candidate gene variants outside the LPA locus with Lp(a) plasma levels in 14,500 participants of six White European cohorts
Zabaneh D., Kumari M., Sandhu M., Wareham N., Wainwright N., Papamarkou T., Hopewell J., Clarke R., Li KW., Palmen J., Talmud PJ., Kronenberg F., Lamina C., Summerer M., Paulweber B., Price J., Fowkes G., Stewart M., Drenos F., Shah S., Shah T., Casas JP., Kivimaki M., Whittaker J., Hingorani AD., Humphries SE.
Background: Both genome-wide association studies and candidate gene studies have reported that the major determinant of plasma levels of the Lipoprotein (a) [Lp(a)] reside within the LPA locus on chromosome 6. We have used data from the HumanCVD BeadChip to explore the contribution of other candidate genes determining Lp(a) levels. Methods: 48,032 single nucleotide polymorphisms (SNPs) from the Illumina HumanCVD BeadChip were genotyped in 5059 participants of the Whitehall II study (WHII) of randomly ascertained healthy men and women. SNPs showing association with Lp(a) levels of p<10 -4 outside the LPA locus were selected for replication in a total of an additional 9463 participants of five European based studies (EAS, EPIC-Norfolk, NPHSII, PROCARDIS, and SAPHIR). Results: In Whitehall II, apart from the LPA locus (where p values for several SNPs were <10 -30) there was significant association at four loci GALNT2, FABP1, PPARGC1A and TNFRSFF11A. However, a meta-analysis of the six studies did not confirm any of these findings. Conclusion: Results from this meta analysis of 14,522 participants revealed no candidate genes from the HumanCVD BeadChip outside the LPA locus to have an effect on Lp(a) levels. Further studies with genome-wide and denser SNP coverage are required to confirm or refute this finding. © 2011 Elsevier Ireland Ltd.