Gunjaca Grgo, Boban Mladen, Pehlić Marina, Zemunik Tatijana, Budimir Danijela, Kolcić Ivana, Lauc Gordan, Rudan Igor, Polasek Ozren
University of Split School of Medicine, Split, Croatia.
Croat Med J. 2010 Feb;51(1):23-31. doi: 10.3325/cmj.2010.51.23.
To investigate the value of genomic information in prediction of individual serum uric acid concentrations.
Three population samples were investigated: from isolated Adriatic island communities of Vis (n=980) and Korcula (n=944), and from general population of the city of Split (n=507). Serum uric acid concentration was correlated with the genetic risk score based on 8 previously described genes: PDZK1, GCKR, SLC2A9, ABCG2, LRRC16A, SLC17A1, SLC16A9, and SLC22A12, represented by a total of 16 single-nucleotide polymorphisms (SNP). The data were analyzed using classification and regression tree (CART) and general linear modeling.
The most important variables for uric acid prediction with CART were genetic risk score in men and age in women. The percent of variance for any single SNP in predicting serum uric acid concentration varied from 0.0%-2.0%. The use of genetic risk score explained 0.1%-2.5% of uric acid variance in men and 3.9%-4.9% in women. The highest percent of variance was obtained when age, sex, and genetic risk score were used as predictors, with a total of 30.9% of variance in pooled analysis.
Despite overall low percent of explained variance, uric acid seems to be among the most predictive human quantitative traits based on the currently available SNP information. The use of genetic risk scores is a valuable approach in genetic epidemiology and increases the predictability of human quantitative traits based on genomic information compared with single SNP approach.
研究基因组信息在预测个体血清尿酸浓度方面的价值。
对三个群体样本进行了研究:来自维斯岛(n = 980)和科尔丘拉岛(n = 944)与世隔绝的亚得里亚海岛屿社区,以及来自斯普利特市的普通人群(n = 507)。血清尿酸浓度与基于8个先前描述的基因的遗传风险评分相关:PDZK1、GCKR、SLC2A9、ABCG2、LRRC16A、SLC17A1、SLC16A9和SLC22A12,由总共16个单核苷酸多态性(SNP)代表。使用分类与回归树(CART)和一般线性模型对数据进行分析。
CART预测尿酸的最重要变量在男性中是遗传风险评分,在女性中是年龄。任何单个SNP在预测血清尿酸浓度时的方差百分比在0.0% - 2.0%之间。使用遗传风险评分解释了男性尿酸方差的0.1% - 2.5%,女性为3.9% - 4.9%。当将年龄、性别和遗传风险评分用作预测因子时,获得的方差百分比最高,在汇总分析中总计为30.9%。
尽管解释的方差总体百分比较低,但基于目前可用的SNP信息,尿酸似乎是预测性最强的人类数量性状之一。与单个SNP方法相比,使用遗传风险评分是遗传流行病学中的一种有价值的方法,并且提高了基于基因组信息的人类数量性状的可预测性。