and etiologically informative, it is very unlikely that this SNP score could be utilized in any way in a personalized medicine context. There are many theories as to why no sizable genetic effects have been discovered for complex traits (Manolio, et al., 2009). Among these are the possibility that complex traits arise from polygenic inheritance where large numbers of common SNPs have individually small effects but account for considerable variance in aggregate (e.g., see (Allen, et al., 2010; Visscher, Yang, & Goddard, 2010; Yang, et al., 2010)). Other possibilities include rare variants that may have individually large effects, such as rare nonsense or missense SNPs or copy-number variants such as insertions/deletions, or variants related to gene expression and regulation (e.g., see (Altshuler, et al., 2010; Montgomery, Lappalainen, Gutierrez-Arcelus, & Dermitzakis, 2011). Undoubtedly, future work will be able to combine common tag SNPs from genome-wide arrays with rare and structural variation from sequencing into much more statistically powerful and biologically interpretable risk scores.
