Empirically, there is ample support for both class of effect. As of June 2011, the NHGRI GWAS catalog lists 1,449 genome-wide significant associations with 237 traits and diseases, spread across all chromosome except the Y99. Some of these may be due to LD with rare variants, but parsimony suggests most are common variant effects. MutDB112(http://mutdb.org/) contains a much larger number of rare coding variants that are either associated with disease or predicted to be damaging. As more individuals are sequenced, many of these appear in healthy controls, but it must be recognized that even large effect alleles are subject to background modification and incomplete penetrance. Initial resequencing of genes identified by GWAS113 has produced mixed results: only 1 of 63 genes in an initial screen for inflammatory bowel disease found evidence for rare variant effects (and these were protective114, but see also115), whereas a significant excess of rare coding variants was found in 4 genes for hypertriglyceridemia116. Considerable resolution of the burden of deleterious rare variants will no doubt emerge in the next few years as whole exome and genome
