Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, nineteen associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biologic pathways.

In India, Tibetans have been living at different altitudes for more than 40 years. This study describes physical growth in terms of height, weight, sitting height, skinfold thickness at triceps and upper arm circumference of Tibetans born and raised at three Tibetan refugee settlements (3,521; 970; and 800 m) from the view point of the hypothesis that growth is retarded at high altitude. Samples consist of individuals between the ages of 2 and 40 years. Tibetans at high altitude in India show a growth pattern similar to that previously observed among Tibetans in Tibet. Tibetans at high altitude are taller and heavier compared to Andean highlanders. The general trends show that Tibetan children and adults of both sexes at low altitude in India are advanced in terms of height, weight, skinfold thickness at triceps and upper arm circumference compared to Tibetans at high altitude. Trunk length (sitting height) is similar at the two altitudes but relative sitting height is greater at high altitude. Greater relative sitting height and lesser leg length at high altitude than at low altitudes is discussed in terms of effect of altitude, temperature, and nutritional status.

Lower BP values among Tibetan children and adolescents at high altitude suggest that altitude affects BP as previously hypothesized, but only in youth. Similar BP in adults at low and high altitudes may reflect the effects of other variables on BP. Measures of adiposity (SFT, BMI and MUAC) have a significant effect on BP. Increase in BP with adult age is observed in Tibetans, which is similar to the pattern observed among populations undergoing modernization.

We report the variation in birth weight among the Tibetans at different altitudes in India to test the hypothesis of greater protection from intrauterine growth retardation (IUGR) among Tibetan compared with other high-altitude native populations. We found that the birth weight of Tibetans at Leh (3521 m, high altitude) is quite similar to what has been reported previously for Tibetans at similar altitudes and is significantly higher than the low-altitude native populations living at similar altitudes. Tibetan birth weights are greater than those of other ethnic groups, both at high and low altitudes. Compared with Tibetans at high altitude (Leh, India; 3521 m), Tibetans at low altitudes (Bylakuppe, India; 800 m and Chandragiri, India; 970 m) have heavier birth weights. This finding is similar to what has been observed previously for other high-altitude native populations. Greater protection from IUGR is not observed for Tibetans compared with other high-altitude native populations as was reported previously. Genetic potential for birth weight is seemingly manifested only at low altitude.

No abstract