Although the heritability of vitamin D status appears considerable 
, the specific genetic determinants of vitamin D levels are only beginning to be identified. Herein, in one of the first studies of genetic determinants of 25(OH)D levels involving African Americans, we found significant associations with three SNPs in vitamin D pathway genes, all of which replicate earlier findings in populations of European ancestry (rs2282679 
, rs2298849 
, rs10877012 
). Importantly, included among these was rs2282679, a highly significant result from two recent GWAS 
, one of which reported a 49% increased risk for vitamin D insufficiency (<20 ng/mL) associated with the rs2282679 minor allele among Caucasians 
. Among African Americans, we found the risk of vitamin D insufficiency associated with the GT or GG genotype for rs2282679 to be similarly elevated (OR
1.70) although not statistically significant (p
0.12). It is notable that we found no significant associations for Caucasians in our study, the size of which was relatively small, and power limitations might explain why we failed to detect a signal among Caucasians. Because African Americans have lower baseline levels of 25(OH)D than Caucasians and may not benefit equally from sunlight-mediated vitamin D synthesis due to heavy skin melanization, genetic influences on 25(OH)D may be relatively more important in determining overall vitamin D status among African Americans and easier to detect in smaller studies. The only previous study of genetic predictors of 25(OH)D among African Americans involved 513 African Americans from 42 families in Los Angeles, CA, and evaluated 30 SNPs in GC
, and CYP27B1 
. Although the examined SNPs included two of the three for which we found an association (rs2298849 and rs10877012), significant findings were reported only for the GC
SNPs rs7041 and rs4588 
Factors related to sunlight (e.g., UVR, season, time spent outdoors, latitude, leisure time physical activity), diet, and other characteristics (e.g., age, adiposity, self-reported race, smoking, alcohol drinking) have been shown to account for about 20–40% of the variability in circulating 25(OH)D 
. To date, the estimated contribution of several identified SNPs to variation in 25(OH)D is generally less than 5% 
, although with further investigation this should increase. Among African Americans in our study, the genotype score based on three SNPs alone could account for 4.6% of the variation in 25(OH)D, whereas UVR score alone could account for 11.9% and diet 4.8%. It is important to note that the highest genotype score among African Americans was associated with an average reduction in serum 25(OH)D of 7.1 ng/mL; in context, this is not trivial given that mean serum 25(OH)D levels among African Americans are typically in the range of 10–20 ng/mL 
We previously reported that, among African Americans, serum 25(OH)D levels decreased 1.0 ng/mL with each 10% increase in African ancestry 
. We did not find evidence in this analysis, however, that the SNPs examined would account for these findings. Of the three SNPs that were associated with vitamin D levels, African Americans across the spectrum of ancestry had similar genotypes. This was contrary to our expectation that genotypes associated with the lowest 25(OH)D levels might be more common in individuals with the highest African ancestry. Our earlier findings may be a result of genetic variation not captured in this specific analysis, or skin color gradations along the spectrum of African ancestry, or both.
Our study is one of the first evaluations in African Americans of genetic determinants of vitamin D levels, and to our knowledge the first to evaluate how genotypes associated with vitamin D status vary in relation to African ancestry. Another strength of this investigation is its base in a generalizable population rather than patient groups. One limitation of the study is our reliance on a single measurement of 25(OH)D as representative of the subjects' general vitamin D status. However, in a separate analysis of 225 SCCS participants who provided two blood samples 1 to 3 years apart, we found a very high correlation (r
0.91, p<0.001) between the two measured 25(OH)D levels (unpublished). The small size of our study and the lack of a replication group are additional limitations, and it will be important to seek replication of these findings in larger samples of African Americans.
In conclusion, we found that common genetic variation does play a role in determining 25(OH)D levels in African Americans, and we were able to replicate key recent findings regarding GC and CYP27B1 SNPs reported from populations of European descent, which were paradoxically not evident in our Caucasian study group. Establishing a genetic underpinning of vitamin D levels among African Americans who are at particularly high risk for vitamin D deficiency would be an important advancement in our understanding of the drivers of vitamin D status and may provide further insights into the causes of certain racial health disparities. As the current body of work moves forward, it will be important to include discovery stage GWAS and larger candidate gene studies among African Americans. Such work may enable the identification of subgroups of African Americans especially in need of vitamin D-related interventions.