28 February 2019

Recently, our project collaborated with Dr. Jiucun Wang named A gene-based recessive diplotype exome scan discovers FGF6, a novel hepcidin-regulating iron-metabolism gene was accepted by Blood

Standard analyses applied to genome-wide association data are well designed to detect additive effects of moderate strength. However, the power for standard genome-wide association study (GWAS) analyses to identify effects from recessive diplotypes is not typically high. We proposed and conducted a gene-based compound heterozygosity test to reveal additional genes underlying complex diseases. With this approach applied to iron overload, a strong association signal was identified between the fibroblast growth factor–encoding gene, FGF6, and hemochromatosis in the central Wisconsin population. Functional validation showed that fibroblast growth factor 6 protein (FGF-6) regulates iron homeostasis and induces transcriptional regulation of hepcidin. Moreover, specific identified FGF6 variants differentially impact iron metabolism. In addition, FGF6 downregulation correlated with iron-metabolism dysfunction in systemic sclerosis and cancer cells. Using the recessive diplotype approach revealed a novel susceptibility hemochromatosis gene and has extended our understanding of the mechanisms involved in iron metabolism. …

Authors of the study are Shicheng Guo#, Shuai Jiang#, Narendranath Epperla, Yanyun Ma, Mehdi Maadooliat, Zhan Ye, Brent Olson, Minghua Wang, Terrie Kitchner, Jeffrey Joyce, Peng An, Robert Strenn, Joseph J. Mazza, Fudi Wang, Jennifer K. Meece, Wenyu Wu, Li Jin, Judith A. Smith, Jiucun Wang* and Steven J. Schrodi*. This study was supported by the Clinical and Translational Science Award (CTSA) program (1UL1RR025011), the National Center for Advancing Translational Sciences (NCATS) grant (9U54TR000021), NCATS grant UL1TR000427 and Marshfield Clinic Research Institute grant SCH10218 and generous donors to the Marshfield Clinic Health System. Authors contributed equally to the work, *Corresponding authors: Dr. Jiucun Wang and Dr. Steven J. Schrodi. …

Some other papers need to be read related to this project:

  • Properties and Modeling of GWAS when Complex Disease Risk Is Due to Non-Complementing, Deleterious Mutations in Genes of Large Effect

Continue reading at https://www.nature.com/articles/s41598-019-47411-1

  • All the figures are only used for non-profit education. reminding me if infrigement happens

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