Contribution of Rare Variants of the SLC22A12 Gene to the Missing Heritability of Serum Urate Levels-Reference-Cited by-同舟云学术

Contribution of Rare Variants of the SLC22A12 Gene to the Missing Heritability of Serum Urate Levels

Published:2020-04-01 Issue:4 Volume:214 Page:1079-1090
ISSN:1943-2631
Container-title:Genetics
language:en
Short-container-title:

Author:

Misawa Kazuharu¹²³¹,Hasegawa Takanori⁴¹,Mishima Eikan⁵¹,Jutabha Promsuk⁶⁷,Ouchi Motoshi⁷,Kojima Kaname²,Kawai Yosuke⁸,Matsuo Masafumi⁹¹⁰,Anzai Naohiko⁷¹¹,Nagasaki Masao²¹²¹³

Affiliation:

1. Department of Genome Analysis, Institute of Biomedical Science, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan

2. Tohoku Medical Megabank Organization, Tohoku University, Sendai, Miyagi 980-8573, Japan

3. RIKEN Center for Advanced Intelligence Project, 1-4-1 Nihonbashi, Chuo-ku, Tokyo 103-0027 Japan

4. Health Intelligence Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan

5. Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Hospital, Sendai, Miyagi 980-8574, Japan

6. Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Bang Phli, Samut Prakan 10540, Thailand

7. Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Tochigi 321-0293, Japan

8. National Center for Global Health and Medicine, Tokyo 162-8655, Japan

9. KNC Department of Nucleic Acid Drug Discovery, Faculty of Rehabilitation, Kobe Gakuin University, Nishi, Kobe 651-2180, Japan

10. Research Center for Locomotion Biology, Kobe Gakuin University, Nishi, Kobe, 651-2180, Japan

11. Department of Pharmacology, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan

12. Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Shogoinkawaramachi 53, Sakyo-ku, Kyoto 606-8507, Japan

13. Human Biosciences Unit for the Top Global Course, Center for the Promotion of Interdisciplinary Education and Research (CPIER), Kyoto University, Shogoinkawaramachi 53, Sakyo-ku, Kyoto 606-8507, Japan

Abstract

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.

Publisher

Oxford University Press (OUP)

Subject

Genetics

Link

https://academic.oup.com/genetics/article-pdf/214/4/1079/42105877/genetics1079.pdf

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