Genome-wide association study for erythrocyte traits and platelet in Chinese Holstein cattle

<b>3.1 Erythrocyte traits results</b> The GWAS results is shown in Table1. And the results are also visualrized by Manhattan plots and corresponding quantile-quantile plots(QQ-plots), which are shown in Figure1 and Figure2. We performed a genome-wide association study for six traits of erythrocyte traits: red blood cell(RBC),mean corpuscular haemoglobin(MCH),mean corpuscular haemoglobin concentration(MCHC),mean corpuscular volume(MCV),haematocrit(HCT),and haemoglobin(HGB). After analysed by Farm-CPU, there are in total twenty three significant SNPs associated with erythrocyte traits: six for RBC, two for MCH, seven for MCHC, two for MCV, four for HCT and two for HGB.Three of these twenty-three SNPs fall into the regions that related with hepatoma (liver cancer), carcinoma of the rectum (colorectal cancer) and cancer, which are harboured within regions of known genes. Other two SNPs fall into regions that have been reported to harbour QTL for Alzheimer’s disease and regulating and controlling of hemameba (WBC) and phagocyte, which fall into regions of known genes. Others are located 11157 to 89626bp away from the nearest known genes. All SNPs are not assigned to any chromosome but all significant SNPs reached genome-wide level. We find KCNJ2 as an candidate gene meanwhile the SNP (BOVINEHD1900016940) on Bos taurus chromosome (BTA)19 was located in the known gene(KCNJ2), and 13Mbp away nearby the gene, which was highly associated with RBC(p= 1.93E-07). <b>3.2 Platelet traits results</b> The GWAS study for platelet contain five traits: platelet count(PLT),platelet distribution width(PDW),mean platelet volume(MPV),large platelet count ratio(LPCR),platelet distribution wide ratio(PDWR).Twenty-seven significant SNPs were detected to be associated with five platelet traits: none for PLT, five for PDW, eleven for MPV, five for LPCR, five for PDWR. The association of these 27 highly significant SNP loci with immunity, cancer occurrence, cancer suppression and health-related traits has not been clearly verified. Moreover, among these 27 significant SNPs, 10SNPs are harboured within regions of nearest known genes, these SNPs are located from 2709 to 621763 bp away from the nearest genes. But none is assigned to any chromosome. And the GWAS results are shown in Table2. Results are also visualrized via Manhattan plots and corresponding quantile-quantile plots(QQ-plots), which are shown in Figure3 and Figure4.

3.1 红细胞性状研究结果
本全基因组关联研究（Genome-Wide Association Study, GWAS）的结果见表1，同时通过曼哈顿图（Manhattan plot）与对应的分位数-分位数图（QQ图，quantile-quantile plot, QQ-plot）进行可视化，结果展示于图1和图2。本研究针对6项红细胞性状开展全基因组关联分析：红细胞（red blood cell, RBC）、平均红细胞血红蛋白量（mean corpuscular haemoglobin, MCH）、平均红细胞血红蛋白浓度（mean corpuscular haemoglobin concentration, MCHC）、平均红细胞体积（mean corpuscular volume, MCV）、血细胞比容（haematocrit, HCT）及血红蛋白（haemoglobin, HGB）。经Farm-CPU分析后，共筛选得到23个与红细胞性状显著关联的单核苷酸多态性位点（single nucleotide polymorphism, SNP）：其中与红细胞相关的位点有6个，与平均红细胞血红蛋白量相关的2个，与平均红细胞血红蛋白浓度相关的7个，与平均红细胞体积相关的2个，与血细胞比容相关的4个，与血红蛋白相关的2个。上述23个位点中，有3个位于与肝癌（hepatoma, liver cancer）、直肠癌（carcinoma of the rectum, colorectal cancer）及癌症相关的已知基因区域内；另外2个位点位于已报道存在阿尔茨海默病相关数量性状位点（quantitative trait locus, QTL）以及调控hemameba（WBC）与吞噬细胞功能的已知基因区域内；剩余位点则距离最近的已知基因11157~89626bp不等。所有显著关联位点均未锚定到具体染色体，但均达到全基因组显著性水平。本研究筛选得到候选基因KCNJ2：位于牛（Bos taurus）19号染色体（BTA19）上的SNP位点BOVINEHD1900016940即位于该基因区域内，且与红细胞（RBC）呈高度显著关联（p=1.93×10^-7），距离该基因约13Mbp。
3.2 血小板性状研究结果
针对血小板性状的全基因组关联研究共包含5项指标：血小板计数（platelet count, PLT）、血小板分布宽度（platelet distribution width, PDW）、平均血小板体积（mean platelet volume, MPV）、大血小板比率（large platelet count ratio, LPCR）及血小板分布宽度比率（platelet distribution wide ratio, PDWR）。共筛选得到27个与5项血小板性状显著关联的SNP位点：其中与血小板计数无显著关联位点，与血小板分布宽度相关的有5个，与平均血小板体积相关的有11个，与大血小板比率相关的有5个，与血小板分布宽度比率相关的有5个。上述27个高度显著关联位点与免疫功能、癌症发生、癌症抑制及其他健康相关性状的关联尚未得到明确验证。此外，27个位点中有10个位于最近的已知基因区域内，其余位点距离最近的已知基因2709~621763bp不等，且所有位点均未锚定到具体染色体。本研究的全基因组关联分析结果见表2，同时通过曼哈顿图与对应的分位数-分位数图（QQ图）进行可视化，结果展示于图3和图4。