Dataset Information

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.

SUBMITTER: Misawa K

PROVIDER: S-EPMC7153932 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Contribution of Rare Variants of the <i>SLC22A12</i> Gene to the Missing Heritability of Serum Urate Levels.

Misawa Kazuharu K Hasegawa Takanori T Mishima Eikan E Jutabha Promsuk P Ouchi Motoshi M Kojima Kaname K Kawai Yosuke Y Matsuo Masafumi M Anzai Naohiko N Nagasaki Masao M

Genetics 20200131 4

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 <i>SLC22A12</i> gene that affec ...[more]

PMID: 32005656

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Project description:ObjectiveTo systematically test dietary components for association with serum urate levels and to evaluate the relative contributions of estimates of diet pattern and inherited genetic variants to population variance in serum urate levels.DesignMeta-analysis of cross sectional data from the United States.Data sourcesFive cohort studies.Review methods16?760 individuals of European ancestry (8414 men and 8346 women) from the US were included in analyses. Eligible individuals were aged over 18, without kidney disease or gout, and not taking urate lowering or diuretic drugs. All participants had serum urate measurements, dietary survey data, information on potential confounders (sex, age, body mass index, average daily calorie intake, years of education, exercise levels, smoking status, and menopausal status), and genome wide genotypes. The main outcome measures were average serum urate levels and variance in serum urate levels. ? values (95% confidence intervals) and Bonferroni corrected P values from multivariable linear regression analyses, along with regression partial R2 values, were used to quantitate associations.ResultsSeven foods were associated with raised serum urate levels (beer, liquor, wine, potato, poultry, soft drinks, and meat (beef, pork, or lamb)) and eight foods were associated with reduced serum urate levels (eggs, peanuts, cold cereal, skim milk, cheese, brown bread, margarine, and non-citrus fruits) in the male, female, or full cohorts. Three diet scores, constructed on the basis of healthy diet guidelines, were inversely associated with serum urate levels and a fourth, data driven diet pattern positively associated with raised serum urate levels, but each explained ?0.3% of variance in serum urate. In comparison, 23.9% of variance in serum urate levels was explained by common, genome wide single nucleotide variation.ConclusionIn contrast with genetic contributions, diet explains very little variation in serum urate levels in the general population.

Dataset Information

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

Publications

Contribution of Rare Variants of the <i>SLC22A12</i> Gene to the Missing Heritability of Serum Urate Levels.

Similar Datasets

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