<b>Objective. </b>Polygenic
prediction of type 2 diabetes in<b> </b>continental Africans is adversely affected
by the limited number of genome-wide association studies (GWAS) of type 2
diabetes from Africa and the poor transferability of European derived polygenic
risk scores (PRS) in diverse ethnicities. We set out to evaluate if African
American, European or multi-ethnic derived PRSs would improve polygenic
prediction in continental Africans.
<p><b>Research
Design and Methods</b>. Using the PRSice software, ethnic-specific PRSs were
computed with weights from the type 2 diabetes GWAS multi-ancestry
meta-analysis of 228,499
cases and 1,178,783 controls. The South
African Zulu study (1602
cases and 981 controls) was used as the target data set. Validation and assessment of the best
predictive PRS association with age at diagnosis was done in the Africa America
Diabetes Mellitus (AADM) study (2148 cases and 2161 controls).</p>
<p> <b>Results. </b>The discriminatory ability of the African American and
Multi-ethnic PRS were similar. However<b>, </b>the African American derived PRS
was more transferable in all the countries represented in the AADM cohort, and
predictive of type 2 diabetes in the country combined analysis compared to the
European and multi-ethnic derived scores. Notably, participants in the 10<sup>th</sup>
decile of this PRS had a 3.63-fold greater risk (OR 3.63; 95%CI (2.19 - 4.03),
p = 2.79 x 10<sup>-17</sup>) per risk allele of developing diabetes and were
diagnosed 2.6 years earlier compared to those in the first decile. </p>
<p><b>Conclusions
</b>African American derived PRS enhances polygenic prediction of type 2 diabetes
in continental Africans. Improved representation of non-European populations
(including Africans) in GWAS promises to provide better tools for precision
medicine interventions in type 2 diabetes.</p>
Genome-Wide Linkage and Admixture Mapping of Type 2 Diabetes in African American Families From the American Diabetes Association GENNID (Genetics of NIDDM) Study Cohort