The combination of synthetic lines and natural diversity when performing combined QTL and association mapping studies represent an opportunity to draw the full picture of the genetic based variation for quantitative traits and ultimately to identify the causal mutations. This approach was performed in order to decipher the genetic architecture of anthocyanin composition in berry skin, a crucial trait for both wine quality and human nutrition. Grapes may either be white or colored, ranging from the lightest pink to the darkest purple tones according to the amount of anthocyanins accumulated in the berry skin. Based on the study of total content of anthocyanins in the skin of mature berries of both a segregating population of 180 progenies and a core collection of natural resources (141 individuals), we identified 2 QTLs for the traits accounting for 62 and 7.1 % of the total variation respectively. With the positional information provided through this QTL mapping, we identified in both cases, MybA candidate genes and identified SNPs markers in high linkage with total content of skin anthocyanins. Using a multivariate regression method, we demonstrated that six polymorphisms accounted for 86% of the observed variation. All these polymorphisms either led to structural changes in the MYB proteins or differences in the VvMybAs promoters. Colour tones of skin are not only due to the overall pigment concentration but also to the presence of different types of pigments and in particular the level of methylation. Similar analysis was performed for the level of anthocyanin methylation in the skin of mature berries. Two QTLs were identified accounting for 37 and 17% of the trait variation respectively. Association mapping, transcriptomic analysis and enzymatic tests enabled the identification of 2 mutations in a structural gene functionally linked to the difference in methylation of anthocyanins. The use of natural diversity thus helped to reduce QTL to a set of QTNs and gave a clear picture on how isogenes combined their effects to shape a quantitative traits and on the relative influence of different cis-and trans-regulatory elements.