Elevated plasma homocysteine levels represent a risk factor for many complex diseases, including cardiovascular disease. Plasma homocysteine, a sulphur containing amino-acid, is a quantitative trait with a complex architecture, affected by multiple genetic and environmental factors. Using the classical twin model, plasma homocysteine levels showed to be highly heritable with a heritability estimate of 48%, warranting efforts in identifying genetic variants associated with this complex trait. A large meta-analysis of ten GWAS on plasma homocysteine levels with a total sample of 44,147 individuals has identified 13 genetic loci associated with plasma homocysteine levels, of which six were novel, located at or near HNF1A, CUBN, MMACHC, FUT2, SLC17A3, GTPBP10, while the rest of seven loci were previously known associations located at or near MTHFR, DPEP1, CBS, NOX4, CPS1, MTR and MUT gene. These findings provide novel insights into the genetic architecture of plasma homocysteine contributing to improving the understanding of the biological mechanisms underlying plasma homocysteine variation.