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Interestingly, our study found multiple genetic associations with LEPR, GHRL and SNPs in other energy regulatory genes, though the adjusted q-values were >0.10.
Furthermore, multiple genetic associations for T2DM [ 7, 17] and body mass index (BMI) [ 18] have been discovered.
8 In European populations, linkage disequilibrium between ITGAM variants leads to multiple genetic associations and difficulty pinpointing functional effects to a single variant.
Despite the discovery of multiple genetic associations with RA, variants within the HLA-DRB1 locus, (that is, HLA-DRB1*04 alleles), remain the most significant contributors to the risk of autoantibody-positive RA [ 8– 14].
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Genes are the unit of analysis or interpretation of multiple genetic association studies.
In the past decade there have been significant efforts towards a systematic evaluation of the multiple genetic association studies for Alzheimer's disease, while the first genome-wide association studies are now being reported with promising results.
Through multiple genetic association studies, such as the genome-wide association study (GWAS) we have discovered many common variants associated with complex disease; however, these variants confer very little disease risk and cumulatively explain a limited portion of heritability (Manolio et al., 2009).
These data suggest that there may be multiple independent genetic associations in the KRT1 interval with HEK migration rate.
To examine the application of FAM-MDR to determine epistasis in family studies of a complex disease, we examined data on glucose area-under-the-curve (GAUC), an endophenotype of Type 2 Diabetes Mellitus (T2DM) for which multiple independent genetic associations have been observed, in the extended pedigrees of the Amish Family Diabetes Study [41] (AFDS).
As Type 2 Diabetes Mellitus (T2DM) is a complex phenotype likely influenced by gene-gene interactions, we applied FAM-MDR to examine data on glucose area-under-the-curve (GAUC), an endophenotype of T2DM for which multiple independent genetic associations have been observed, in the Amish Family Diabetes Study AFDSS).
Our gene-level analysis makes the assumption that genes likely to show pathway-level effects (see Phase III below) are likely to be involved in multiple pairwise genetic associations within the same gene region and/or with other genes in the same pathway.
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