Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes

The molecular mechanisms involved in the development of type 2 diabetes are poorly understood. Starting from genome-wide genotype data for 1924 diabetic cases and 2938 population controls generated by the Wellcome Trust Case Control Consortium, we set out to detect replicated diabetes association signals through analysis of 3757 additional cases and 5346 controls and by integration of our findings with equivalent data from other international consortia. We detected diabetes susceptibility loci in and around the genes CDKAL1, CDKN2A/CDKN2B, and IGF2BP2 and confirmed the recently described associations at HHEX/IDE and SLC30A8. Our findings provide insight into the genetic architecture of type 2 diabetes, emphasizing the contribution of multiple variants of modest effect. The regions identified underscore the importance of pathways influencing pancreatic beta cell development and function in the etiology of type 2 diabetes.     

A genome-wide association study of five meat quality traits in Yorkshire pigs

Meat quality is an important trait in the pig industry. To identify genomic regions and haplotype blocks responsible for meat quality traits in pigs, a genome-wide association study was conducted for five traits including intramuscular fat content, pH at 45 min and 24 h, drip loss within 24 h and water-holding capacity in 231 Yorkshire barrows using illumina porcine 60k SNP chips. The results showed that a total of 344 single nucleotide polymorphisms (SNP) were significantly associated with five meat quality traits (P<1×10^-4). Moreover, 323 SNPs were within the reported QTL regions, of which 21 were novel. Also, 158 SNPs fell into the proximal region of meat quality related genes. In addition, 25 haplotype blocks based on 116 SNPs were revealed with SNP combination patterns for five traits. Our study added new SNP information for identification of meat quality traits in pigs and will help elucidate the mechanisms of meat quality in pigs.     

Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels

New strategies for prevention and treatment of type 2 diabetes (T2D) require improved insight into disease etiology. We analyzed 386,731 common single-nucleotide polymorphisms (SNPs) in 1464 patients with T2D and 1467 matched controls, each characterized for measures of glucose metabolism, lipids, obesity, and blood pressure. With collaborators (FUSION and WTCCC/UKT2D), we identified and confirmed three loci associated with T2D-in a noncoding region near CDKN2A and CDKN2B, in an intron of IGF2BP2, and an intron of CDKAL1-and replicated associations near HHEX and in SLC30A8 found by a recent whole-genome association study. We identified and confirmed association of a SNP in an intron of glucokinase regulatory protein (GCKR) with serum triglycerides. The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases.     

A genome-wide association study identifies IL23R as an inflammatory bowel disease gene

The inflammatory bowel diseases Crohn's disease and ulcerative colitis are common, chronic disorders that cause abdominal pain, diarrhea, and gastrointestinal bleeding. To identify genetic factors that might contribute to these disorders, we performed a genome-wide association study. We found a highly significant association between Crohn's disease and the IL23R gene on chromosome 1p31, which encodes a subunit of the receptor for the proinflammatory cytokine interleukin-23. An uncommon coding variant (rs11209026, c.1142G>A, p.Arg381Gln) confers strong protection against Crohn's disease, and additional noncoding IL23R variants are independently associated. Replication studies confirmed IL23R associations in independent cohorts of patients with Crohn's disease or ulcerative colitis. These results and previous studies on the proinflammatory role of IL-23 prioritize this signaling pathway as a therapeutic target in inflammatory bowel disease.     

全基因组关联分析在茶叶研究中的应用进展

全基因组关联分析（genome-wide association analysis,GWAS）是以高通量测序技术为基础,结合生物信息学和统计学方法,在全基因组水平上鉴定调控复杂性状的基因变异,是研究复杂农艺性状和遗传变异最有力和最有效的研究方法,其核心是研究遗传变异和目标性状之间的关联。GWAS研究检测到的关联位点一般很少,而且关联的位点仅能解释很少一部分性状变异。本文介绍了影响GWAS的主要因素,总结了GWAS在茶叶饮料消费、茶树重要农艺性状、茶叶品质和茶树群体结构研究中取得的一系列进展,提出了茶树GWAS研究中遇到的问题和未来的发展方向。     

Mining of candidate genes for grape berry cracking using a genome-wide association study

Fruit cracking is a common phenomenon during the growth and development of horticultural crops that seriously affects fruit yield and quality. However, there are few studies on the mining of candidate genes related to berry cracking. To better understand the genetic basis of grape berry cracking, we conducted a genome-wide association study(GWAS)of grape varieties. Based on the mixed linear model(MLM), we detected five single nucleotide polymorphism(SNP)loci associated with berry-cracking index ...     

广东汉族人群JAK2 rs7849191位点单核甘酸多态性与2型糖尿病遗传易感性研究

目的 了解JAK2 rs7849191位点单核苷酸多态性(SNP)与2型糖尿病遗传易感性关系.方法 采用SNPscanTM分型技术检测广东地区汉族人群中1 092例2型糖尿病患者和1 092名正常对照JAK2 rs7849191位点基因型,比较两组中基因型及等位基因频率分布.结果 糖尿病患者和正常对照中JAK2 rs7849191位点的等位基因频率和基因型频率分布差异无统计学意义(P＞0.05).结论 广东地区汉族人群中2型糖尿病患者遗传易感性可能与JAK2 rs7849191位点SNP无关.     

Integration of genome-wide association study and selection signatures reveals genetic determinants for skeletal muscle production traits in an F2 chicken population

Improving the production of broiler chicken meat has been a goal of broiler breeding programs worldwide for many years. However, the genetic architectures of skeletal muscle production traits in chickens have not yet been fully elucidated. In the present study, a total of 519 F₂ birds, derived from a cross of Arbor Acres broiler and Baier layer, were re-sequenced(26 F₀ individuals were re-sequenced at a 10-fold depth; 519 F₂ individuals were re-sequenced at a 3-f...     

Identification and validation of novel loci associated with wheat quality through a genome-wide association study

Understanding the genetic basis of quality-related traits contributes to the improvement of grain protein concentration(GPC), grain starch concentration(GSC), and wet gluten concentration(WGC) in wheat. In this study, a genome-wide association study(GWAS) based on a mixed linear model(MLM) was performed on 236 wheat accessions, including 160 cultivars and 76 landraces, using a 55K single nucleotide polymorphism(SNP) array in multiple environments. A total of 12 stable QTL/SNPs that control diffe...     

数量性状全基因组关联分析中上位效应遗传位点检测方法研究进展

数量性状的表型变异受到大量效应微小的遗传位点和诸多环境因素的共同作用,但在数量性状的遗传研究领域,关于不同遗传位点之间加性效应与上位效应相对重要性的认识却存在着分歧。近年来,伴随着全基因组关联分析在人类及家养动物数量性状研究中的发展,在全基因组关联分析的框架内进行上位效应遗传位点的检测越发受到重视。文章以遗传力失踪问题为出发点,首先综述了标记-QTL连锁分析和GWAS框架下传统上位效应遗传位点的检测方法,然后对基于表型方差同质性检验和广义线性混合模型方法的上位效应统计推断以及混杂因素的处理方法进行了总结与梳理,旨在为数量性状全基因规模上位效应的相关研究提供理论参考。     

持续皮下胰岛素输注与多次胰岛素皮下注射对2型糖尿病强化治疗的效果比较

目的比较持续皮下胰岛素输注(CSII)和多次胰岛素皮下注射(MSII)在2型糖尿病强化降糖中的效果。方法将48例2型糖尿病患者随机分成CSII组(n=26)和MSII组(n=22)两组,CSII组的患者采用胰岛素泵降糖治疗,MSII组的患者采用胰岛素笔降糖治疗。监测两组患者治疗前后全天血糖谱的变化,观察并比较血糖达标所需要的时间、胰岛素用量、低血糖发生率等情况。结果CSII组与MSII组相比,血糖达标所需的时间、胰岛素用量及低血糖发生率等差异有显著统计学意义(P<0.01)。结论持续皮下胰岛素输注和多次胰岛素皮下注射对2型糖尿病患者强化降糖治疗均有效,但胰岛素泵降糖效果优于胰岛素笔。     

Genetic dissection of hexanol content in soybean seed through genome-wide association analysis

Hexanol is a major compound contributing to the off-flavors(the bean-like odor) of soybean derived soymilk. The most effective way to reduce the off-flavors of soymilk is the screening and utilization of soybean cultivars with improved hexanol content. However, no genome-wide genetic analysis for this particular trait has been conducted to date. The objective of the present study was to dissect the genetic basis of hexanol content in soybean seed through genome-wide association analysis(GWAS). A total of 105 soybean accessions were analyzed for hexanol content in a three-year experiments and genotyped by sequencing using the specific locus amplified fragment sequencing(SLAF-seq) approach. A total of 25 724 single nucleotide polymorphisms(SNPs) were obtained with minor allele frequencies(MAF)5%. GWAS showed that 25 quantitative trait nucleotides(QTNs) were significantly associated with the hexanol concentration in soybean seed. These identified QTNs distributed on different genomic regions of the 15 chromosomes. A total of 91 genes were predicted as candidate genes underlying the seed hexanol level and six candidates were predicted possibly underlying the seed hexanol by gene based association. In this study, GWAS has been proven to be an effective way to dissect the genetic basis of the hexanol concentration in multiple genetic backgrounds. The identified beneficial alleles and candidate genes might be valuable for the improvement of marker-assisted breeding efficiency for low hexanol level and help to explore possible molecular mechanisms underlying hexanol content in soybean seed.     

Genetic dissection of the grain-filling rate and related traits through linkage analysis and genome-wide association study in bread wheat

Wheat grain yield is generally sink-limited during grain filling. The grain-filling rate (GFR) plays a vital role but is poorly studied due to the difficulty of phenotype surveys. This study explored the grain-filling traits in a recombinant inbred population and wheat collection using two highly saturated genetic maps for linkage analysis and genome-wide association study (GWAS). Seventeen stable additive quantitative trait loci (QTLs) were identified on chromosomes 1B, 4B, and 5A. The linkage interval between IWB19555 and IWB56078 showed pleiotropic effects on GFR₁, GFR_max, kernel length (KL), kernel width (KW), kernel thickness (KT), and thousand kernel weight (TKW), with the phenotypic variation explained (PVE) ranging from 13.38% (KW) to 33.69% (TKW). 198 significant marker-trait associations (MTAs) were distributed across most chromosomes except for 3D and 4D. The major associated sites for GFR included IWB44469 (11.27%), IWB8156 (12.56%) and IWB24812 (14.46%). Linkage analysis suggested that IWB35850, identified through GWAS, was located in approximately the same region as QGFRmax2B.3-11, where two high-confidence candidate genes were present. Two important grain weight (GW)-related QTLs colocalized with grain-filling QTLs. The findings contribute to understanding the genetic architecture of the GFR and provide a basic approach to predict candidate genes for grain yield trait QTLs.     

利用全基因组关联分析挖掘粳稻直链淀粉含量调控基因

直链淀粉含量是评价稻米蒸煮食味品质关键指标,挖掘控制该性状QTLs/基因对于改良稻米品质具有重要意义.研究利用295份粳稻种质组成的自然群体为试验材料,测定2019年和2020年稻米直链淀粉含量,结合重测序得到788 396个高质量SNP,利用Tassel 5.0软件混合线性模型(MLM,Q+K)作全基因组关联分析.结果表明,两年共检测到12个与稻米直链淀粉含量相关QTL,分布在水稻第3、4、11和12染色体上,贡献率范围为8.78％～11.62％,其中qAAC4-2和qAAC12-2在两年中重复检测到.进一步针对这两个QTL区间内所有基因作单倍型分析,结合基因注释和前人研究结果,推测LOC_Os04g33640为影响稻米直链淀粉含量新候选基因.     

影响二甲双胍初治2型糖尿病效果因素分析

目的 调查常见几种影响二甲双胍治疗2型糖尿病的因素,为使用二甲双胍初治2型糖尿病提供依据。方法 以初诊的117例2型糖尿病患者作为研究对象,对影响二甲双胍初治2型糖尿病效果进行评估。选择年龄、性别、体质量指数(BMI)、血压、空腹血糖(FBG)、餐后2 h血糖(2hPG)、空腹胰岛素(FINS)、糖化血红蛋白(HbA₁C)、总胆固醇(TC)和胰岛素抵抗指数(HOMA-IR)等因素进行分组考查,比较各组中二甲双胍初治疗效的差异性。结果 经二甲双胍初治3个月后,BMI、FBG、2hPG、FINS、HbA₁C和TC水平均明显下降,较治疗前均差异有统计学意义(P＜0.05)。FINS和HOMA-IR等因素对二甲双胍初治2型糖尿病的影响显著(P＜0.05)。结论 FINS和HOMA-IR可能是影响二甲双胍初治2型糖尿病疗效的重要因素。     

2型糖尿病患者微血管病变与血液流变学变化、胰岛素抵抗的相关性

目的 :研究血液流变学变化和胰岛素抵抗与 2型糖尿病微血管病变的关系。方法 :检测 10 6例 2型糖尿病患者 ,其中有微血管并发症 5 3例 ,无微血管并发症 5 3例 ,以及 5 3例正常对照组的血液流变学、空腹血糖、空腹胰岛素 ,计算胰岛素敏感性指数 (ISI) ,并进行比较。结果 :糖尿病两组全血粘度和血浆粘度均显著高于正常对照组 ;ISI则显著低于正常对照组 (P<0 .0 1)。糖尿病有微血管病变组全血粘度和血浆粘度显著高于无微血管病变组 ;ISI显著低于无微血管病变组 (P<0 .0 1)。多元逐步回归分析显示 ,2型糖尿病微血管病变与糖尿病病程、血糖、全血粘度和血浆粘度呈显著正相关 (r=0 .62 4,0 .42 8,0 .3 46,0 .3 82 ,P值分别 <0 .0 0 1,0 .0 1,0 .0 5 ,0 .0 1) ,与 ISI呈显著负相关 (r=-0 .3 5 2 ,P<0 .0 5 )。结论 :2型糖尿病微血管病变患者存在持续性的高血糖、高血液粘度 ,糖尿病病程的延长 ,严重的胰岛素抵抗为 2型糖尿病微血管病变的主要危险因素。     

进入生殖嵴前PGCs中H2A变体的分布

小鼠原始生殖细胞进入生殖嵴之前经历细胞迁移、大量繁殖。为进一步解分子调控机制,文章通过组织石蜡切片免疫荧光染色和单细胞免疫荧光染色技术,对8.5、10.5 dpcPGCs中组蛋白H2A变体MacroH2A、H2A.Z、H2A. X的分布情况进行研究。结果表明,8.5~10.5 dpc,H2A.Z在PGCs中的表达明显递增,10.5 dpc PGCs中H2A.Z的表达主要集中于细胞核;而MacroH2A和H2A.X在此过程中无明显变化,在细胞质和细胞核中弱表达。综合分析发现,8.5~10.5 dpc PGCs中H2A.Z可能是装配核小体的主要变体,PGCs大量繁殖可能有H2A.Z的参与。     

3种H2A变体在卵原及前体细胞中的分布研究

通过组织石蜡切片和单细胞免疫荧光染色及定量PCR技术,对卵原及前体细胞中组蛋白H2A变体macroH2A、H2A.Z、H2A.X的分布情况进行了研究。结果表明:12.5 dpc细胞中3种组蛋白H2A变体荧光强度减弱,macroH2A在11.5 dpc、12.5 dpc的细胞质中表达,有少量沉积,13.5 dpc细胞质中macroH2A沉积明显增多。H2A.X在11.5 dpc、12.5 dpc细胞核质中弥散分布,13.5 dpc时主要集中于细胞核表达。H2A.Z在11.5 dpc细胞核质区都有表达,在12.5 dpc细胞质内表达减弱的同时细胞核中表达增强,13.5 dpc时主要集中在细胞质中表达。不同时期组蛋白H2A 3种变异体定量PCR结果与免疫荧光技术分析结果一致。由此推断,组蛋白H2A变体的分布可能与细胞的性别分化及减数分裂相关。