Effects of genetic ancestry and socioeconomic deprivation on ethnic differences in serum creatinine

The inclusion of ethnicity in equations for estimating the glomerular filtration rate (eGFR) from serum creatinine levels has been challenged since ethnicity is socially defined and therefore a poor proxy for biological differences. We hypothesized that genetic ancestry (GA) would be more strongly associated with creatinine levels among healthy individuals than self-identified ethnicity. We studied a diverse cohort of 35,590 participants characterized as part of the UK Biobank, grouped by self-reported ethnicity: Black, East Asian, Mixed, Other, South Asian, and White. We used multivariable modeling to test for associations between ethnicity, GA, socioeconomic deprivation, and serum creatinine levels, including covariates for age, sex, height, and body mass index. Model fit comparisons and relative importance analysis were used to compare the effects of ethnicity and GA on creatinine levels. Black ethnicity shows a positive effect on participant serum creatinine levels (I) = 9.36 +/- 0.38), whereas East Asian (I) = -1.80 +/- 0.66) and South Asian (I) = -0.28 +/- 0.36) ethnicity show negative effects on creatinine. Male sex (I) = 17.69 +/- 0.34) and height (I) = 0.13 +/- 0.02) also show high positive associations with creatinine levels, while socioeconomic deprivation (I) = -0.04 +/- 0.04) shows no significant association. African ancestry has the highest association (I) = 13.81 +/- 0.52) with creatinine levels. Overall, GA (9.06%) explains significantly more of the variation in creatinine levels than ethnicity (4.96%), with African ancestry (6.36%) alone explaining more of the variation than ethnicity. We found that GA explains more of the variation in serum creatinine levels than socioeconomic deprivation, suggesting the possibility that ethnic differences in creatinine are shaped by genetic rather than social factors.

Automated summary

The inclusion of ethnicity in estimating glomerular filtration rate (eGFR) from creatinine levels has been challenged. Genetic ancestry is more strongly associated with creatinine levels than self-identified ethnicity, suggesting that ethnic differences in creatinine may be shaped by genetic factors rather than social factors.