Pinpointing the specific genes involved is a challenging task, given that the MHC is characterized both by extreme diversity of specific loci, and by extreme and complex linkage disequilibrium patterns that must be tightly controlled for to avoid confusing findings due to linkage disequilibrium from true association.
In this study, for the identification of possible cis-regulatory polymorphisms we first analyzed the region surrounding BRCA2, which shows very complex linkage disequilibrium.
Nonetheless, co-localization of signals for several correlated traits and diseases (adiposity, UL, age-at-menopause, serum SHBG, predisposing for prostate cancer) to a genomic region overlapping the lncRNA locus may reflect complex linkage disequilibrium between 1q43 loci with significant effect size, pleiotropy or coordinated gene expression (Aissani 2014).
Unlike gene expression data for which both the technologies and methods have matured, GWAS data analysis presents numerous challenges, including testing millions of SNPs per sample and subsequent multiple test corrections, complex local linkage disequilibrium (LD) structures, and heavy computational duties due to thousands of samples, especially in permutation analysis.
This could be explained in part by the variation of HLA phenotype frequencies in these white national or ethnic groups or by other genes within the major histocompatibility complex in linkage disequilibrium that also play a major role in mediation of immune responses.
Although more recent studies have improved study design, investigators are still challenged by the complex patterns of linkage disequilibrium across this gene-dense region, and by the disease heterogeneity characteristic of all genetically complex disorders.
As expected, we observed a complex pattern of linkage disequilibrium with neighbouring SNPs (data not shown).
A limitation of this analysis is that the SNPs, which are linkage disequilibrium with complex disease variants, were not considered for the functional effect annotation analysis.
The quasi paucity of express saccades could be due to the disequilibrium of complex cortical/subcortical networks needed for making express saccades.
Analyses of other genes in the MHC complex found in linkage disequilibrium with the DRB1*13 alleles may also give insight to this protective effect.
