Common and ethnic-specific genetic determinants of hemoglobin concentration between Taiwanese Han Chinese and European Whites: findings from comparative two-stage genome-wide association studies

Human iron nutrition is a result of interplays between genetic and environmental factors. However, there has been scarcity of data on the genetic vari-ants associated with altered iron homeostasis and ethnic-specific associations are further lacking. In this study, we compared between the Taiwanese Han Chinese (HC) and European Whites the genetic determinants of hemoglobin (Hb) concentration, a biochemical parameter that in part reflects the amount of functional iron in the body. Through sex-specific two-stage genome-wide association studies (2S-GWAS), we observed the consistent Hb-association of SNPs in TMPRSS6 (chr 22), ABO (chr 9), and PRKCE (chr 2) across sexes in both ethnic groups. Specific to the Taiwanese HC, the Hb-association of AXIN1, together with other loci near the chr 16 alpha-globin gene cluster, was found novel. On the other hand, majority of the Hb-associated SNPs among Europeans were identified along the chr 6 major histocompatibility complex (MHC) region, which has established roles in immune system control. We report here strong Hb-associations of HFE and members of gene families (SLC17; H2A, H2B, H3, H4, H1; TRIM; ZSCAN, ZKSCAN, ZNF; HLA; BTN, OR) , numerous SNPs in/nearby CARMIL1, PRRC2A, PSORS1C1, NOTCH4, TSBP1, C6orf15, and distinct associations with non-coding RNA genes. Our findings provide evidence for both common and ethnic-specific genetic determinants of Hb between East Asians and Caucasians. These will help to further our understanding of the iron and/or ery-thropoiesis physiology in humans and to identify high risk subgroups for iron imbalances - a primary requirement to meet the goal of precision nutrition for optimal health. (c) 2022 Published by Elsevier Inc.

Automated summary

Human iron nutrition is influenced by both genetic and environmental factors. This study compared the genetic determinants of hemoglobin (Hb) concentration between Taiwanese Han Chinese and European Whites. The results showed consistent associations of specific SNPs in TMPRSS6, ABO, and PRKCE with Hb levels in both ethnic groups. Ethnic-specific associations were also observed, such as the association of AXIN1 with Hb levels in Taiwanese Han Chinese. The findings highlight the importance of both common and ethnic-specific genetic factors in Hb regulation.