72 research outputs found
Transferability of Type 2 Diabetes Implicated Loci in Multi-Ethnic Cohorts from Southeast Asia
Recent large genome-wide association studies (GWAS) have identified multiple loci
which harbor genetic variants associated with type 2 diabetes mellitus (T2D),
many of which encode proteins not previously suspected to be involved in the
pathogenesis of T2D. Most GWAS for T2D have focused on populations of European
descent, and GWAS conducted in other populations with different ancestry offer a
unique opportunity to study the genetic architecture of T2D. We performed
genome-wide association scans for T2D in 3,955 Chinese (2,010 cases, 1,945
controls), 2,034 Malays (794 cases, 1,240 controls), and 2,146 Asian Indians
(977 cases, 1,169 controls). In addition to the search for novel variants
implicated in T2D, these multi-ethnic cohorts serve to assess the
transferability and relevance of the previous findings from European descent
populations in the three major ethnic populations of Asia, comprising half of
the world's population. Of the SNPs associated with T2D in previous GWAS,
only variants at CDKAL1 and
HHEX/IDE/KIF11 showed the strongest
association with T2D in the meta-analysis including all three ethnic groups.
However, consistent direction of effect was observed for many of the other SNPs
in our study and in those carried out in European populations. Close examination
of the associations at both the CDKAL1 and
HHEX/IDE/KIF11 loci provided some evidence of locus and
allelic heterogeneity in relation to the associations with T2D. We also detected
variation in linkage disequilibrium between populations for most of these loci
that have been previously identified. These factors, combined with limited
statistical power, may contribute to the failure to detect associations across
populations of diverse ethnicity. These findings highlight the value of
surveying across diverse racial/ethnic groups towards the fine-mapping efforts
for the casual variants and also of the search for variants, which may be
population-specific
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