Your question might be more of an engineering line of reasoning, but it's still hardware related.
Consider the mounting points for your mainboard. They are "scattered" around the board based on standards for case mount placement. They are almost certainly engineered to take stress from the components on the board and transfer that to the stand-offs attached to the case.
In that configuration, the forces are more-or-less evenly distributed over the mainboard, perhaps with additional mount holes near high-load areas such as the processor and heat sink assembly.
I have assembled a couple computer boards which did not have stand-offs in the case but had mounting holes. This was a flaw or failure in the case engineering but had little effect on the installation.
In your case, literally and figuratively, you would want to ensure that every mounting hole was properly secured and supported the board. If your intent is to secure the mainboard only at the edges, I would suggest that is contra-indicated. To secure all of the points, it would be necessary to build "branches" from behind the board to secure where possible, or in front of the board, providing support from either side.
The best support will be provided by branches that are perpendicular to the mainboard. Those that are not would allow some flex in the structure. If one cannot create a perpendicular-to-the-board branch, one should consider both a vertical and a horizontal branch joined at the mount point.
I would not suggest that it is "wiser" to avoid such a construction, as the other factors for this design have not been referenced.