Ammon here. We are in a data-limited environment where regularization is key. That's why LASSO regression has worked so well. Linearity itself (low parameter count) is regularization. Anything else (done naively) does not generalize. Of course, a (surprisingly) large amount of human variation does appear to be due to additive effects, and is thus well explained by linear models. But that's not the entire story. PRS models for many diseases still fall far short of broad-sense heritability. There is a gap to explain. The question, I think, comes does to the ... (read more)
Ammon here. We are in a data-limited environment where regularization is key. That's why LASSO regression has worked so well. Linearity itself (low parameter count) is regularization. Anything else (done naively) does not generalize. Of course, a (surprisingly) large amount of human variation does appear to be due to additive effects, and is thus well explained by linear models. But that's not the entire story. PRS models for many diseases still fall far short of broad-sense heritability. There is a gap to explain. The question, I think, comes does to the ... (read more)