"major issue of" is correct and usable in written English.
It is often used to introduce a noun that is part of a larger problem or issue. For example, "Climate change is a major issue of our time."
Metastasis is a major issue of treatment in the majority of human tumors, including TSCC.
The strongly contested award recognises an article of "a major issue of public interest or concern".
At some point back in summer 2014, housing because a major issue of protest again.
After 1918 Fiume-Rijeka became a major issue of the postwar peace settlements.
The major issue of the 1888 presidential campaign was the protective tariff.
A major issue of principle and large amounts of money are at stake.
Dengue virus is a major issue of tropical and sub-tropical regions.
In Tunisia, the building sector is considered as a major issue of energy consumption.
One major issue of automatic classification is the feature-selection method from high-dimensional data.
The importance of governance and cultural adaptation has become a major issue of concern.
Luka Modric's future has been the major issue of the summer and it seems pivotal to Tottenham's prospects.
