Like our other 2 SNPs, rs2229741 and rs4986938 are not amino acid changing variants, being intronic and part of the 3′ UTR of their genes respectively, and it is possible that the weakness of the associations we have identified also indicate linkage to functional polymorphisms nearby.
Linkage analysis exploits the shared inheritance of functional polymorphisms and adjacent markers within families or pedigrees of known ancestry, whereas association analysis is an approach to detect QTL localization based on linkage disequilibrium in unrelated individuals or natural populations.
These polymorphisms, including MTHFR C677T in our research, were all striking examples of functional polymorphisms being strongly selected for in human population in response to environmental stresses.
MiRNA-polymorphisms (miR-polymorphisms or miRSNPs) are a novel class of functional polymorphisms present in the human genome [33], [34].
This implies that Alu-D-type might associate with higher ACE serum activity because of the tight linkage with functional polymorphisms, which belong to stalk domain of ACE.
Bobes, M. A. et al. Linkage of functional and structural anomalies in the left amygdala of reactive-aggressive men.
Alternatively, the rs2297630 SNP might be a functionally neutral marker that is in linkage disequilibrium with a functional polymorphism located elsewhere at the SDF1 locus.
Thus, the significance of the association may be brought up by still unknown mechanisms or by linkage disequilibrium (LD) with functional polymorphisms.
Third, the SNPs assayed in the association analyses could be too distant from (or not in linkage disequilibrium with) the functional polymorphism in the gene.
Sst I polymorphism is located in 3′-untranslated 3′-untranslatedpoC3 gene, and it is possible that this polymoregion is in linkage disequilibrium with ofher functhenApoC3lymorphism in the nearby regene, such andT-455C polymorphitm.
A genome-wide linkage analysis conducted with Japanese KD sib-pair samples revealed several linked regions, and led to the identification of a functional polymorphism in the ITPKC (inositol 1,4,5-triphosphate 3-kinase C) gene [11], [12].
