@article{31a6015653864bb4b777baa52b9cf3b1,
title = "Contribution of rare variants of the SLC22A12 gene to the missing heritability of serum urate levels",
abstract = "Gout is a common arthritis caused by monosodium urate crystals. The heritability of serum urate levels is estimated to be 30-70%; however, common genetic variants account for only 7.9% of the variance in serum urate levels. This discrepancy is an example of “missing heritability.” The “missing heritability” suggests that variants associated with uric acid levels are yet to be found. By using genomic sequences of the ToMMo cohort, we identified rare variants of the SLC22A12 gene that affect the urate transport activity of URAT1. URAT1 is a transporter protein encoded by the SLC22A12 gene. We grouped the participants with variants affecting urate uptake by URAT1 and analyzed the variance of serum urate levels. The results showed that the heritability explained by the SLC22A12 variants of men and women exceeds 10%, suggesting that rare variants underlie a substantial portion of the “missing heritability” of serum urate levels.",
keywords = "Cohort study, Environmental factors, Genetic factors, Heritability, Metabolic syndrome, Rare variants, Serum uric acids, Transporter",
author = "Kazuharu Misawa and Takanori Hasegawa and Eikan Mishima and Promsuk Jutabha and Motoshi Ouchi and Kaname Kojima and Yosuke Kawai and Masafumi Matsuo and Naohiko Anzai and Masao Nagasaki",
note = "Funding Information: Promotion of Science (JSPS) KAKENHI grant number JP17K08682 and Tohoku Medical Megabank Project (Special Account for reconstruction from the Great East Japan Earthquake), Grant Number JP19km0105001, JP15km0105002. All computational resources were provided by the ToMMo supercomputer system (http://sc.megabank.tohoku.ac.jp/en). Funding Information: We are indebted to all the volunteers who participated in this Tohoku Medical Megabank Organization (ToMMo) project. We would like to thank members of ToMMo at Tohoku University for their seminal contribution to establishing the genome cohort and biobank, and help with genome analyses. The list of members of ToMMo at Tohoku University is available on the following website, https:// www.megabank.tohoku.ac.jp/english/a191201/. We would also like to thank the members of Iwate Tohoku Medical Megabank Organization at Iwate Medical University. We thank Ms. Noriko Ohshima for her technical assistance. We also thank Mr. Toshiya Hatanaka for drawing the figure of URAT1. This work was supported by Japan Society for the Publisher Copyright: {\textcopyright} 2020 Misawa et al.",
year = "2020",
month = apr,
day = "1",
doi = "10.1534/GENETICS.119.303006",
language = "English",
volume = "214",
pages = "1079--1090",
journal = "Genetics",
issn = "0016-6731",
publisher = "Oxford University Press",
number = "4",
}