Contribution of Rare Variants of the SLC22A12 Gene to the Missing Heritability of Serum Urate Levels
Contribution of Rare Variants of the SLC22A12 Gene to the Missing Heritability of Serum Urate Levels
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DOI：
10.1534/genetics.119.303006
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发表时间：
2020-04-01
期刊：
影响因子：
3.3
通讯作者：
Nagasaki, Masao
中科院分区：
文献类型：
--
作者：
Misawa, Kazuharu;Hasegawa, Takanori;Nagasaki, Masao
痛风是一种常见的关节炎引起的尿酸盐晶体。血清尿酸水平的遗传率估计为30-70%;然而，常见的遗传变异仅占血清尿酸水平变异的7.9%。这种差异是“缺失遗传性”的一个例子。通过使用ToMMo队列的基因组序列，我们确定了影响URAT 1尿酸转运活性的SLC 22 A12基因的罕见变异。URAT 1是由SLC 22 A12基因编码的转运蛋白。我们将受试者与影响URAT 1尿酸盐摄取的变异体分组，并分析血清尿酸盐水平的方差。结果表明，男性和女性的SLC 22 A12变异解释的遗传力超过10%，这表明罕见变异是血清尿酸水平“缺失遗传力”的重要组成部分。
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.