Novel and previously reported genomic loci that associate with serum folate levels at P−9.

Association results for serum folate in Icelandic and Danish study samples separately and combined. The effect allele is the allele associated with increased serum folate levels. The effect is on a quantile normalized scale. Data were combined in fixed effect meta-analyses based on P-value and direction of effect adjusted for the number of individuals in each sample. Values of I2 are percentages. Association between serum folate levels and MTHFR rs1801133 in the Inter99 cohort has been published previously [14]. Chr., chromosome; EAF, effect allele frequency; HET, heterogeneity; SNV, single nucleotide variant.1The annotation is based on the RefSeq hg18.2The reference allele based on Build 36 hg18 is shown in bold.3In the Icelandic data a 2 bp INDEL in exon 3 of FOLR3 associated more strongly with serum folate levels. As only SNVs were analyzed in the Danish data this data was not available for the Danish samples.4The rs652197 variant was initially discovered in the Icelandic samples but subsequently genotyped in Danish samples to confirm the association.

针对冰岛和丹麦研究样本分别开展及合并开展的血清叶酸关联分析结果。效应等位基因（effect allele）指与血清叶酸水平升高相关的等位基因，效应值以分位数标准化（quantile normalized）尺度呈现。数据采用固定效应meta分析进行合并，合并依据为P值及效应方向，并针对每个样本的个体数量进行了校正。I2值以百分比表示。Inter99队列中血清叶酸水平与MTHFR基因rs1801133位点的关联此前已发表[14]。注：Chr.为染色体（chromosome）；EAF为效应等位基因频率（effect allele frequency）；HET为异质性（heterogeneity）；SNV为单核苷酸变异（single nucleotide variant）。1 本注释基于RefSeq hg18数据库。2 以粗体显示的是基于Build 36 hg18的参考等位基因。3 在冰岛人群数据中，FOLR3基因第3外显子区域的2bp插入缺失（INDEL）与血清叶酸水平的关联强度更高。由于丹麦人群数据仅分析了单核苷酸变异（SNV），因此丹麦样本无该变异的相关数据。4 rs652197变异最初在冰岛样本中被发现，随后在丹麦样本中进行基因分型以验证该关联。