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Summary: Genome-wide association (GWA) studies of common com-
plex or multifactorial diseases have been spectacularly
successful in the last 2 years, with many new loci iden-
tified with levels of probability that were once thought
unattainable. However, the extraordinary levels of sig-
nificance of the association signals have yet to be trans-
lated into a full understanding of the genes or genetic
elements that are mediating disease susceptibility at
particular loci.
The functional effects of DNA polymorphism on
multifactorial disease can be mediated through several
mechanisms. Polymorphisms that alter protein function
canhaveveryimportanteffects,suchasNOD2(nucleotide-
binding oligomerization domain-containing 2; also
known as CARD15) mutations in inflammatory bowel
disease1
and FLG (filaggrin) mutations in eczema
(atopic dermatitis)2
. However, systematic study of com-
plex diseases with known non-synonymous SNPs has
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