Additional families informative at these DRD2 loci are needed to determine whether these functional variants or another functional polymorphism in LD with rs1800498 is responsible for the increased risk for autism.
Characterization of the mechanisms by which these variants, or other functional variants in strong linkage disequilibrium, influence risk for disease will provide a better understanding of the biology of disease.
For these rare variants, single variant tests can lack power, and association tests that group rare variants by gene or functional unit are favored (Li and Leal, 2008; Lin and Tang, 2011; Madsen and Browning, 2009; Price et al., 2010; Wu et al., 2011).
However, it is unknown whether rs9272143 is the pathogenic variant or other functional variant(s) which affect(s) the expression of HLA-DRB1 could be responsible for this signal.
On the other hand, the GWAS signals are functionally unbiased but have largely not been attributed to causal or functional variants in genes.
Power can be boosted by using statistical approaches to aggregate rare variants across chromosomal regions or functional units.
Towards this goal, transethnic GWAS designs use naturally occurring differences in the LD patterns surrounding the locus of interest to help identify the likely causal or functional variants(s).
Furthermore, in the past few years, the genomics community has shifted its focus from locus discovery to identifying casual or functional variants, in response to heavy criticisms of the limited utility of GWAS results and in an effort to better establish whether there is significant utility of such genetic information.
As for many genome-wide association studies, we could not narrow the association to a single gene or functional variant.
Different alleles of a candidate gene that underlie a QTL must display either an expression or functional variant.
