The exponential distribution of Vg is compatible with numerous rare variants with large RR or numerous common variants with small RR, or a combination of both.
With respect to genetic factors, genome-wide association studies (GWAS), composed of large cohorts of AD and controls, identified numerous common variants but with smaller risks associated with development of late-onset AD [ 4].
For most of the population, however, pre-eclampsia seems to represent a complex genetic disorder, and occurs as the result of numerous common variants at different loci which, individually, have small effects but collectively contribute to an individual's susceptibility to disease.
Furthermore, there is disagreement concerning whether common traits are caused by numerous common genetic variants (the common disease/common variant theory) or by rare, population specific mutations.
This has not happened, largely because drug response phenotypes, like many other phenotypes, are probably the net effects of numerous common genetic variants of small effect, and uncommon interacting variants of unknown effect size.
Numerous common genetic variants associated with atrial fibrillation risk have been identified [ 19- 22] and rare genetic variants are expected to improve the detection of at-risk individuals [ 23, 24].
Numerous common genetic variants with small effects on blood pressure have been identified as well as some rare genetic variants with large effects on blood pressure but the genetic basis of hypertension is still poorly understood.
The motivational impact of DTC testing where personal genetic risk is based on numerous common genetic variants and is even more probabilistic has yet to be assessed in a realistic scenario.
To date, numerous common genetic variants associated with common disease [e.g. Type 1 diabetes (T1D)] have been successfully discovered by genome-wide association studies (Barrett et al., 2009; Cooper et al., 2008; Smyth et al., 2006; Wellcome Trust Case Control Consortium, 2007).
Apart from the original translocation mutation, and a C-terminal frame-shift four nucleotide deletion in DISC1, both of which have the potential to encode protein truncations, numerous nonsynonymous common variants and ultrarare missense mutations in DISC1 have been associated with major mental illness.
Recent theoretical work has suggested that numerous T2DM-associated common variants remain to be identified (18), and it remains to be seen if, when summed together, they will improve discrimination of future cases.
