GWAS in people of Middle Eastern descent reveals a locus protective of kidney function-a cross-sectional study

Type 2 diabetes is one of the leading causes of chronic kidney failure, which increases globally and represents a significant threat to public health. People from the Middle East represent one of the largest immigrant groups in Europe today. Despite poor glucose regulation and high risk for early-onset insulin-deficient type 2 diabetes, they have better kidney function and lower rates of all-cause and cardiovascular-specific mortality compared with people of European ancestry. Here, we assessed the genetic basis of estimated glomerular filtration rate (eGFR) and other metabolic traits in people of Iraqi ancestry living in southern Sweden.

Genome-wide association study (GWAS) analyses were performed in 1201 Iraqi-born residents of the city of Malmö for eGFR and ten other metabolic traits using linear mixed-models to account for family structure.

The strongest association signal was detected for eGFR in CST9 (rs13037490; P value = 2.4 × 10^-13), a locus previously associated with cystatin C-based eGFR; importantly, the effect (major) allele here contrasts the effect (minor) allele in other populations, suggesting favorable selection at this locus. Additional novel genome-wide significant loci for eGFR (ERBB4), fasting glucose (CAMTA1, NDUFA10, TRIO, WWC1, TRAPPC9, SH3GL2, ABCC11), quantitative insulin-sensitivity check index (METTL16), and HbA1C (CAMTA1, ME1, PAK1, RORA) were identified.

The genetic effects discovered here may help explain why people from the Middle East have better kidney function than those of European descent. Genetic predisposition to preserved kidney function may also underlie the observed survival benefits in Middle Eastern immigrants with type 2 diabetes.