Contribution of rare variants of the SLC22A12 gene to the missing heritability of serum urate levels

Kazuharu Misawa, Takanori Hasegawa, Eikan Mishima, Promsuk Jutabha, Motoshi Ouchi, Kaname Kojima, Yosuke Kawai, Masafumi Matsuo, Naohiko Anzai, Masao Nagasaki

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1079-1090
Number of pages12
Issue number4
Publication statusPublished - 2020 Apr 1


  • Cohort study
  • Environmental factors
  • Genetic factors
  • Heritability
  • Metabolic syndrome
  • Rare variants
  • Serum uric acids
  • Transporter


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