Identification of low-frequency variants associated with gout and serum uric acid levels

We tested 16 million SNPs, identified through whole-genome sequencing of 457 Icelanders, for association with gout and serum uric acid levels. Genotypes were imputed into 41,675 chip-genotyped Icelanders and their relatives, for effective sample sizes of 968 individuals with gout and 15,506 individuals for whom serum uric acid measurements were available. We identified a low-frequency missense variant (c.1580C>G) in ALDH16A1 associated with gout (OR = 3.12, P = 1.5 × 10(-16), at-risk allele frequency = 0.019) and serum uric acid levels (effect = 0.36 s.d., P = 4.5 × 10(-21)). We confirmed the association with gout by performing Sanger sequencing on 6,017 Icelanders. The association with gout was stronger in males relative to females. We also found a second variant on chromosome 1 associated with gout (OR = 1.92, P = 0.046, at-risk allele frequency = 0.986) and serum uric acid levels (effect = 0.48 s.d., P = 4.5 × 10(-16)). This variant is close to a common variant previously associated with serum uric acid levels. This work illustrates how whole-genome sequencing data allow the detection of associations between low-frequency variants and complex traits.     

工科线性代数的教学策略研究

线性代数相对与其他课程具有体系感、较强的逻辑性和抽象性、应用非常广和计算量非常大的特点。而当前线性代数教学面临的形势是:任课老师教学工作量大和学生自觉性不高,工科学生学习数学的兴趣比学专业课的兴趣低,工科学生的数学基础普遍降低,课时非常紧张,现在大学生做作业的主动积极性不高。因此,要调动学生的学习积极性,关键在于让学生对这门课感兴趣,要善于启发和引导学生的思维,充分利用多媒体课件,培养或是引导学生的兴趣,要善于引导学生对内容归纳和总结,学会融会贯通。     

中学生物教师继续教育相关问题的调查研究

职后继续教育的课程设置对教师素质有一定的影响,采用问卷调查、文献分析和访谈等方法,对中学生物教师继续教育所应开设的课程、教学形式等继续教育方面的问题进行研究,并提出相应建议。     

Discovery of common variants associated with low TSH levels and thyroid cancer risk

To search for sequence variants conferring risk of nonmedullary thyroid cancer, we focused our analysis on 22 SNPs with a P < 5 × 10(-8) in a genome-wide association study on levels of thyroid stimulating hormone (TSH) in 27,758 Icelanders. Of those, rs965513 has previously been shown to associate with thyroid cancer. The remaining 21 SNPs were genotyped in 561 Icelandic individuals with thyroid cancer (cases) and up to 40,013 controls. Variants suggestively associated with thyroid cancer (P < 0.05) were genotyped in an additional 595 non-Icelandic cases and 2,604 controls. After combining the results, three variants were shown to associate with thyroid cancer: rs966423 on 2q35 (OR = 1.34; P(combined) = 1.3 × 10(-9)), rs2439302 on 8p12 (OR = 1.36; P(combined) = 2.0 × 10(-9)) and rs116909374 on 14q13.3 (OR = 2.09; P(combined) = 4.6 × 10(-11)), a region previously reported to contain an uncorrelated variant conferring risk of thyroid cancer. A strong association (P = 9.1 × 10(-91)) was observed between rs2439302 on 8p12 and expression of NRG1, which encodes the signaling protein neuregulin 1, in blood.