FTO基因rs9939609 A/T多态与多囊卵巢综合征易感性的研究

目的:探讨FTO基因rs9939609 A/T单核苷酸多态性位点与多囊卵巢综合征易感性及其临床生化特征的相关性。方法:选择102例多囊卵巢综合征患者和96例健康女性作为研究对象并收集其病例临床信息,采用突变敏感性分子开关方法检测各受试者FTO基因rs9939609A/T多态,比较多囊卵巢综合征组与对照组基因型与基因频率的差异,分析基因型与临床生化特征的相关性。结果:rs9939609A/T多态位点共检测到TT、AT、AA三种基因型,其在多囊卵巢综合征组与对照组的频率分别为77.5%、21.5%、1.0%,77.1%12.5%10.4%,两者之间存在显著性差异(P=0.006);等位基因T、A的频率在多囊卵巢综合征组(88.2%、11.8%)与对照组(83.3%、16.7%)之间的分布不具有显著性差异;多囊卵巢综合征组与对照组中,TT与AT+AA两基因型群体的临床和生化特征比较均未发现显著性差异。结论:FTO基因rs9939609 A/T多态位点与PCOS易感性存在相关性。     

Association analysis of the FTO gene with obesity in children of Caucasian and African ancestry reveals a common tagging SNP

Recently an association was demonstrated between the single nucleotide polymorphism (SNP), rs9939609, within the FTO locus and obesity as a consequence of a genome wide association (GWA) study of type 2 diabetes in adults. We examined the effects of two perfect surrogates for this SNP plus 11 other SNPs at this locus with respect to our childhood obesity cohort, consisting of both Caucasians and African Americans (AA). Utilizing data from our ongoing GWA study in our cohort of 418 Caucasian obese children (BMI>or=95th percentile), 2,270 Caucasian controls (BMI<95th percentile), 578 AA obese children and 1,424 AA controls, we investigated the association of the previously reported variation at the FTO locus with the childhood form of this disease in both ethnicities. The minor allele frequencies (MAF) of rs8050136 and rs3751812 (perfect surrogates for rs9939609 i.e. both r(2) = 1) in the Caucasian cases were 0.448 and 0.443 respectively while they were 0.391 and 0.386 in Caucasian controls respectively, yielding for both an odds ratio (OR) of 1.27 (95% CI 1.08-1.47; P = 0.0022). Furthermore, the MAFs of rs8050136 and rs3751812 in the AA cases were 0.449 and 0.115 respectively while they were 0.436 and 0.090 in AA controls respectively, yielding an OR of 1.05 (95% CI 0.91-1.21; P = 0.49) and of 1.31 (95% CI 1.050-1.643; P = 0.017) respectively. Investigating all 13 SNPs present on the Illumina HumanHap550 BeadChip in this region of linkage disequilibrium, rs3751812 was the only SNP conferring significant risk in AA. We have therefore replicated and refined the association in an AA cohort and distilled a tag-SNP, rs3751812, which captures the ancestral origin of the actual mutation. As such, variants in the FTO gene confer a similar magnitude of risk of obesity to children as to their adult counterparts and appear to have a global impact.     

Longitudinal replication studies of GWAS risk SNPs influencing body mass index over the course of childhood and adulthood

Genome-wide association studies (GWAS) have identified multiple common variants associated with body mass index (BMI). In this study, we tested 23 genotyped GWAS-significant SNPs (p-value<5*10-8) for longitudinal associations with BMI during childhood (3-17 years) and adulthood (18-45 years) for 658 subjects. We also proposed a heuristic forward search for the best joint effect model to explain the longitudinal BMI variation. After using false discovery rate (FDR) to adjust for multiple tests, childhood and adulthood BMI were found to be significantly associated with six SNPs each (q-value<0.05), with one SNP associated with both BMI measurements: KCTD15 rs29941 (q-value<7.6*10-4). These 12 SNPs are located at or near genes either expressed in the brain (BDNF, KCTD15, TMEM18, MTCH2, and FTO) or implicated in cell apoptosis and proliferation (FAIM2, MAP2K5, and TFAP2B). The longitudinal effects of FAIM2 rs7138803 on childhood BMI and MAP2K5 rs2241423 on adulthood BMI decreased as age increased (q-value<0.05). The FTO candidate SNPs, rs6499640 at the 5 '-end and rs1121980 and rs8050136 downstream, were associated with childhood and adulthood BMI, respectively, and the risk effects of rs6499640 and rs1121980 increased as birth weight decreased. The best joint effect model for childhood and adulthood BMI contained 14 and 15 SNPs each, with 11 in common, and the percentage of explained variance increased from 0.17% and 9.0*10(-6)% to 2.22% and 2.71%, respectively. In summary, this study evidenced the presence of long-term major effects of genes on obesity development, implicated in pathways related to neural development and cell metabolism, and different sets of genes associated with childhood and adulthood BMI, respectively. The gene effects can vary with age and be modified by prenatal development. The best joint effect model indicated that multiple variants with effects that are weak or absent alone can nevertheless jointly exert a large longitudinal effect on BMI.     

Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure

The FTO gene has significant polymorphic variation associated with obesity, but its function is unknown. We screened a population of 150 whites (103F/47M) resident in NE Scotland, United Kingdom, for variants of the FTO gene and linked these to phenotypic variation in their energy expenditure (basal metabolic rate (BMR) and maximal oxygen consumption VO(2)max) and energy intake. There was no significant association between the FTO genotype and BMR or VO(2)max. The FTO genotype was significantly associated (P = 0.024) with variation in energy intake, with average daily intake being 9.0 MJ for the wild-type TT genotype and 10.2 and 9.5 MJ for the "at risk" AT and AA genotypes, respectively. Adjusting intake for BMR did not remove the significance (P = 0.043). FTO genotype probably affects obesity via effects on food intake rather than energy expenditure.     

单羧酸转运蛋白基因SNP 与肝细胞肝癌预后的关联研究

目的:探讨单羧酸转运蛋白基因(monocarboxylate transporter,MCT)单核苷酸多态性(single nucleotide polymorphism,SNPs)与肝细胞肝癌(hepatocellular carcinoma,HCC)根治术患者预后的关系。方法:运用Sequenom i PLEX分型技术对830例原发性HCC患者MCT家族(MCT1、MCT2和MCT4)基因上的8个功能性SNP位点进行基因分型,并分析这些SNP与HCC患者预后的相关性。结果:MCT1基因rs1049434位点和MCT2基因rs995343位点基因型与HCC患者总体生存期及无复发生存期均显著相关(P0.05)。携带MCT1 AT基因型或TT基因型的患者死亡及复发风险均显著低于携带AA基因型的患者(HR=0.72;P=0.042或HR=0.64;P=0.002);携带MCT2 CT基因型或TT基因型的患者死亡及复发风险均显著高于携带CC基因型的患者(HR=1.64;P=0.018或HR=1.52;P=0.026)。而且,MCT1基因rs1049434位点和MCT2基因rs995343位点对HCC预后存在显著的累积效应,携带2个危险基因型的患者死亡及复发风险分别是没有危险基因型患者的2.16倍和2.54倍。此外,携带2个危险基因型的HCC患者在术后行TACE辅助治疗后死亡及复发风险均显著降低(P0.05)。结论:MCT1和MCT2基因上的功能性SNP位点有可能作为HCC根治术后预后评估和TACE辅助治疗反应预测的独立标志物。     

Association of the FTO rs9939609 polymorphism with obesity in Roma/Gypsy population

The rs9939609 SNP located in the first intron of the fat mass and obesity associated gene (FTO) has been found to be associated with common obesity mainly in populations of European descent. The Roma/Gypsy population as an ethnic minority of Asian Indian origin is well known for its adverse health status with a high prevalence of obesity. The main aim of this study was to examine the contribution of the rs9939609 FTO polymorphism to the high prevalence of obesity in the Roma/Gypsy population. Following a number of anthropometric measurements, the FTO rs9939609 polymorphism was genotyped in 312 Roma/Gypsy individuals. We observed significant differences in body mass index (BMI), waist circumference, and waist-to-hip ratio between different genotypes (P = 0.003, P = 0.012, and P = 0.03, respectively). The waist circumference in the subjects with AA genotype was about 7.1 cm larger than in those with TT genotypes (P = 0.005). However, the strongest association of minor allele A of the rs9939609 FTO polymorphism was found with BMI (odds ratio, 1.55; 95% confidence interval, 1.129-2.128; P = 0.007), even after adjusting for age, sex, and smoking status. This study provides the first report of allele and genotype frequencies for the rs9939609 polymorphism and also the first evidence of the association of the FTO variant with obesity in the Roma/Gypsy population.     

Responses to FTO genetic test feedback for obesity in a sample of overweight adults: a qualitative analysis

Current evidence indicates that genetic testing for obesity risk has limited affective or behavioral impact, but few studies have explored the effects among individuals who self-identify as having weight problems. Here, we report findings from in-depth telephone interviews with seven overweight or obese volunteers who were genotyped for one weight-related gene (FTO), which may offer interesting insights into motivations to seek out genetic testing and immediate reactions to it. All participants had a BMI > 25. The gene test identified one participant as homozygous for the ‘higher-risk’ variant (AA), three heterozygous (AT), and three homozygous for the ‘lower-risk’ variant (TT) of FTO. All participants said they took part to find an explanation for their personal struggle with weight control. Those with one or two higher-risk variants experienced relief and saw the result as confirming their private assumption that they were susceptible to weight gain for reasons perceived as ‘external’ to them. However, at the same time, they described themselves as more motivated to overcome their genetic predisposition. Those with lower-risk variants reported brief disappointment, but then focused on alternative explanations, reinforcing the multifactorial nature of obesity. Despite objectively low ‘information value,’ all individuals derived some ‘personal’ benefit from FTO genetic test feedback. However, improving education about the multifactorial nature of complex conditions is important to decrease polarized thinking and associated genetic determinism and stigma to derive the greatest benefits of novel genetic technologies for individuals and their health.     

SDCCAG8 obesity alleles and reduced weight loss after a lifestyle intervention in overweight children and adolescents

Genome-wide association analyses (GWAS) contributed to the detection of a number of single-nucleotide polymorphisms (SNPs) associated with obesity. However, little is known about the impact of the obesity-risk alleles on weight loss-related phenotypes after lifestyle interventions. A recent meta-analysis of GWAS reported five genomic loci near or in the genes FTO, MC4R, TMEM18, SDCCAG8, TNKS/MSRA that were associated with obesity in children and adolescents. Here, we analyzed the effect of the 10 SNPs representative of the five loci on measures of weight loss and cardiometabolic risk after a 1-year lifestyle intervention in 401 children and adolescents (mean age 10.74 years; 55.4% female; mean BMI 27.42 kg/m(2), mean BMI-standard deviation score (SDS) 2.37). For confirmation of one locus genotyping of three intronic SNPs in SDCCAG8 was performed in 626 obese adults who completed the 10-week hypoenergetic diet program. Intronic variants of SDCCAG8, which are associated with early onset obesity, are associated with reduced weight loss after a 1-year lifestyle intervention in overweight children and adolescents even after adjusting for age, sex, baseline measurement, or multiple testing (all P < 10(-6)). However, our results could not be confirmed in 626 obese adults undertaking a hypoenergetic diet intervention.     

FTO influences on longitudinal BMI over childhood and adulthood and modulation on relationship between birth weight and longitudinal BMI

SNP rs9939609 within the fat mass and obesity associated gene (FTO) is strongly associated with adult body mass index (BMI). However, influences of FTO on longitudinal BMI change from childhood to adulthood have not been examined. Knowledge is limited on FTO, modulating the association between birth weight and longitudinal change of BMI. This longitudinal study examined SNPs of FTO in 658 white subjects from childhood (3–17 years) to adulthood (18–45 years). No significant associations of FTO SNPs with either birth weight or longitudinal BMI over childhood were noted after multiple-test adjustment. However, three SNPs (rs9939609, rs17820875 and rs860713) with different inheritance patterns were identified to be associated with longitudinal BMI over adulthood after Bonferroni adjustment (P = 5.3 × 10⁻⁵, 2.0 × 10⁻⁴ and 0.001). In addition, interactions were discovered between birth weight and SNPs of rs17820875 (P = 0.001) and rs860713 (0.002). A negative association between birth weight and adult BMI were found in risk genotype AG of rs17820875 and GG of rs860713 in contrast to positive associations in other genotypes. These findings led to the conclusion that lower birth weight predisposes to higher adult BMI depending on FTO risk genotypes. Our studies underscore the importance of FTO influences on obesity and provide insights into the evolution of the long-term burden of obesity.     

Genetic Influence in Developmental Dysplasia of the Hip in Saudi Arabian Children Due to <Emphasis Type="Italic">GDF5</Emphasis> Polymorphism

Developmental dysplasia of the hip (DDH) is quite common among Saudi Arabian babies. With an objective to assess the presence of SNP rs143383 and the alleles in the GDF5 gene among patients with DDH, parents, and unaffected siblings, we undertook this case-controlled study. We collected and analyzed for a functional single nucleotide polymorphism (SNP) in the 5′-untranslated region of the GDF5 gene (rs143383), 473 blood samples, (100 patients, 200 parents, 73 siblings and 100 healthy controls. We determined the association between the patients’ genotype and their fathers’, mothers’ and siblings’ genotype through Chi-square analysis. The majority of those screened possessed the TC genotype, and 61.8% of patients and their fathers had the TT genotype. There was no association between patients’ and fathers’ genotype, P value?<?0.332, 95% CI (0.328–0.346), and between patients’ and mothers’, P?<?0.006, 95% CI (0.004–0.007). When considering DDH patients’ and the control group’s genotypes, the odds ratios of TT versus other combined (0.641?>?1) and CC versus other combined (0.474?<?1) revealed that the TT genotype has higher risk of developing DDH compared with the CC genotype. The 95 percent confidence interval of TT versus other combined and CC versus other combined is 0.932–2.891 and 0.208–1.078, respectively. For patients’ and fathers’ genotypes, the odds ratios of TT versus other combined (1.275?>?1) and CC versus other combined (0.815?<?1) indicate that the TT genotype has higher risk of exhibiting DDH compared to the CC genotype. For patients’ and siblings’ genotypes, the odds ratios of TT versus other combined (1.669) and CC versus other combined (1.048) specify that the TT genotype possesses higher risk of developing DDH compared with the CC genotype. Our study shows that there exists a relationship between GDF5 (SNP rs143383) and DDH in our population. Second, we found for the first time that the genotype TT and the T allele were overly expressed in the patients and the fathers. More studies on the confirmation of this genetic marker for DDH are called for.     

Functional Polymorphisms of Interferon-gamma Affect Pneumonia-Induced Sepsis

Objective

Sepsis is an inflammatory syndrome caused by infection, and both its incidence and mortality are high. Because interferon-gamma (IFN-γ) plays an important role in inflammation, this work assessed IFN-γ single nucleotide polymorphism (SNPs) that may be associated with sepsis.

Methods

A total of 196 patients with pneumonia-induced sepsis and 213 age- and sex-matched healthy volunteers participated in our study from July 2012 to July 2013 in Guangzhou, China. Patient clinical information was collected. Clinical pathology was assessed in subgroups defined based on clinical criteria, APACHE II (acute physiology and chronic health evaluation) and SOFA (sepsis-related organ failure assessment) scores and discharge rate. Four functional SNPs, −1616T/C (rs2069705), −764G/C (rs2069707), +874A/T (rs2430561) and +3234C/T (rs2069718), were genotyped by Snapshot in both sepsis patients and healthy controls. Pearson’s chi-square test or Fisher’s exact test were used to analyze the distribution of the SNPs, and the probability values (P values), odds ratios (OR) and 95% confidence intervals (CIs) were calculated.

Results

No mutations in the IFN-γ −764G/C SNP were detected among the participants in our study. The +874A/T and +3234C/T SNPs were in strong linkage disequilibrium (LD) (r² = 0.894). The −1616 TC+TT, +874 AT+AA genotype and the TAC haplotype were significantly associated with sepsis susceptibility, while the CTT haplotype was associated with protection against sepsis incidence. Genotype of −1616 TT wasn’t only protective against severity of sepsis, but also against higher APACHE II and SOFA scores as +874 AA and +3234 CC. The TAC haplotype was was protective against progression to severe sepsis either.

Conclusion

Our results suggest that functional IFN-γ SNPs and their haplotypes are associated with pneumonia-induced sepsis.     

Study of Five Pubertal Transition-Related Gene Polymorphisms as Risk Factors for Premature Coronary Artery Disease in a Chinese Han Population

Background

Recently, single nucleotide polymorphisms (SNPs) (DLK-rs10144321, SIX6-rs1254337, MKRN3-rs12148769, LIN28B-rs7759938, and KCNK9-rs1469039) were found to be strongly associated with age at menarche. Recent studies also suggested that age at menarche is a heritable trait and is associated with risks for obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease, and all-cause mortality. Since an association between these five SNPs and premature coronary artery disease (CAD) has never been reported, we investigated whether these SNPs are associated with premature CAD and its severity in a Chinese Han population.

Methods

We enrolled 432 consecutive patients including 198 with premature CAD (<55 years in men and <65 years in women) and 234 controls. All subjects were genotyped for the five SNPs by the PCR-ligase detection reaction method. The associations between these SNPs and premature CAD and its severity were analyzed.

Results

The following genotypes were identified: GG, AG, and AA at rs10144321 and rs12148769; TT, AT, and AA at rs1254337; CC, CT, and TT at rs1469039; and TT and CT at rs7759938. Significant differences in genotype distribution frequencies at rs1254337 were found between controls and patients with premature CAD (P<0.05). No associations were found between the five SNPs and the severity of coronary lesions (all P>0.05). Compared with controls, patients with premature CAD had a higher prevalence of T2DM and dyslipidemia, and the proportion of patients with T2DM rose significantly with an increase in the number of stenosed coronary vessels (all P<0.05). After adjustment for the clinical parameters in multivariable analysis, three factors were identified that significantly increased the risk of premature CAD: the AA genotype at rs1254337 (OR: 2.388, 95% CI: 1.190–4.792, P = 0.014), male gender (OR: 1.565, 95% CI: 1.012–2.420, P = 0.044), and T2DM (OR 2.252, 95% CI: 1.233–4.348, P = 0.015).

Conclusions

Among the five pubertal transition-related gene polymorphisms, we identified an association between rs1254337 and premature CAD in a Chinese Han population.     

中华鳖GHSR基因SNPs的筛选及生长性状的关联分析

为探究GHSR基因多态性对中华鳖(Pelodiscus sinensis)生长相关性状的影响,采用直接测序法在GHSR基因5'侧翼和3'侧翼上筛选SNPs位点,共检测到5个单核苷酸多态性位点:A335T、G397T、A527G、A13482C和T13526A。随机选取同批繁殖的1冬龄200只中华鳖用直接测序法进行SNPs位点的分型,并分析与生长性状的相关性。检测结果显示,所有SNP位点均符合Hardy-Weinberg平衡状态(p>0.05)。方差分析显示,A336T位点的AT、TT基因型的体重、背甲长、背甲宽和裙边宽4项生长数据均显著高于AA基因型。A13482C位点的AC基因型的体重、背甲长、背甲宽和裙边宽4项数据均显著高于AA基因型(p<0.05)。研究表明,本实验在GHSR基因上获得的这些SNP位点可能影响着中华鳖的生长性状或与之紧密连锁,可为中华鳖分子辅助育种提供助力与参考。     

MC4R Variant Is Associated With BMI but Not Response to Resistance Training in Young Females

Recently, a genome‐wide association study (GWAS) that identified eight single‐nucleotide polymorphisms (SNPs) associated with BMI highlighted a possible neuronal influence on the development of obesity. We hypothesized these SNPs would govern the response of BMI and subcutaneous fat to resistance training in young individuals (age = 24 years). We genotyped the eight GWAS‐identified SNPs in the article by Willer et al. in a cohort (n = 796) that undertook a 12‐week resistance‐training program. Females with a copy of the rare allele (C) for rs17782313 (MC4R) had significantly higher BMIs (CC/CT: n = 174; 24.70 ± 0.33 kg/m², TT: n = 278; 23.41 ± 0.26 kg/m², P = 0.002), and the SNP explained 1.9% of overall variation in BMI. Males with a copy of the rare allele (T) for rs6548238 (TMEM18) had lower amounts of subcutaneous fat pretraining (CT/TT: n = 65; 156,534 ± 7,415 mm³, CC: n = 136; 177,825 ± 5,139 mm³, P = 0.019) and males with a copy of the rare allele (A) for rs9939609 (FTO) lost a significant amount of subcutaneous fat with exercise (AT/AA: n = 83; ?798.35 ± 2,624.30 mm³, TT: n = 47; 9,435.23 ± 3,494.44 mm³, P = 0.021). Females with a copy of the G allele for a missense variant in the SH2B1 (rs7498665) was associated with less change of subcutaneous fat volume with exercise (AG/GG: n = 191; 9,813 ± 2,250 mm³ vs. AA: n = 126; 770 ± 2,772 mm³; P = 0.011). These data support the original finding that there is an association between measures of obesity and a variant near the MC4R gene and extends these results to a younger population and implicates FTO, TMEM18, and SH2B1 polymorphisms in subcutaneous fat regulation.     

Association between microRNA-146a, -499a and -196a-2 SNPs and non-small cell lung cancer: a case–control study involving 2249 subjects

MicroRNA (miR) acts as a negative regulator of gene expression. Many literatures have suggested that miRs may be involved in the process of cell proliferation, inflammation, oxidative stress, energy metabolism and epithelial–mesenchymal transition. Thus, miRs may be implicated in the occurrence of non-small cell lung cancer (NSCLC). In the current investigation, we included 2249 subjects (1193 NSCLC patients and 1056 controls) and designed a study to identify the relationship of miR-146a rs2910164 C/G, -499a rs3746444 A/G and -196a-2 rs11614913 T/C with the risk of NSCLC. The risk factors (e.g., body mass index (BMI), sex, smoking, drinking and age) was used to adjust the odds ratios (ORs) and 95% confidence intervals (CIs). After conducting a power value assessment, we did not confirm that the miR-single nucleotide polymorphisms (SNPs) genotypic distributions were different in NSCLC cases and controls. However, the association of miR-196a-2 rs11614913 with a decreased risk of NSCLC was identified in the female subgroup (adjusted P=0.005, power = 0.809 for TC vs. TT, and adjusted P=0.004, power = 0.849 for CC/TC vs. TT). In addition, gene–gene interaction analysis showed that rs11614913 TC/3746444 AA and rs11614913 CC/rs3746444 AA could also reduce the susceptibility to NSCLC (rs11614913 TC/rs3746444 AA vs. rs11614913 TT/rs3746444 AA, P=0.001, power = 0.912 and rs11614913 CC/rs3746444 AA vs. rs11614913 TT/rs3746444 AA, P=0.003, power = 0.836). In conclusion, in overall comparisons, we did not confirm that the rs2910164, rs3746444, and rs11614913 SNPs genotypic distributions were different in NSCLC cases and controls. However, this case–control study demonstrates that miR-196a-2 rs11614913 may be a protective factor for the development of NSCLC among female patients.     

A genetic variant in LINGO2 contributes to the risk of gestational diabetes mellitus in a Chinese population

Genome-wide association studies (GWASs) showed that three single nucleotide polymorphisms (SNPs; rs10968576, rs1412239, and rs824248) in the leucine-rich repeat and Ig domain containing 2 (LINGO2) were associated with obesity or type 2 diabetes (T2D). We aimed to determine the influence of the LINGO2 variants on the gestational diabetes mellitus (GDM) risk. Thus, we performed a case–control study including 964 GDM cases and 1,021 controls to test the associations between the three LINGO2 variants (rs10968576, rs1412239, and rs824248) and susceptibility to GDM. Logistic regression analyses showed no significant association between LINGO2 variations (rs10968576 and rs1412239) and GDM susceptibility, but we observed that LINGO2 rs824248 A > T was significantly associated with an increased risk of GDM using the dominant model (TT/AT vs. AA: adjusted odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.05–1.51; p = 0.012) and the additive model (TT vs. AT vs. AA: adjusted OR = 1.16, 95% CI = 1.03–1.31; p = 0.016). In the additive model, a stronger risk effect of rs824248 was observed among obese women (prepregnancy body mass index [BMI] > 22 kg/m², adjusted OR = 1.34, 95% CI = 1.12–1.59) compared with that in lean women (prepregnancy BMI ≤ 22 kg/m², adjusted OR = 1.0², 95% CI = 0.86–1.21; p = 0.029 for heterogeneity test). Further interactive analyses also detected a significant multiplicative interaction between rs824248 and prepregnancy BMI for the risk of GDM (p = 0.041). These findings indicate that LINGO2 rs824248 may serve as a susceptibility marker for GDM in Chinese females.     

Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium

Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis study in which we assessed whether these two loci are also associated with myopia in other populations. The study population comprised 31 cohorts from the Consortium of Refractive Error and Myopia (CREAM) representing 4 different continents with 55,177 individuals; 42,845 Caucasians and 12,332 Asians. We performed a meta-analysis of 14 single nucleotide polymorphisms (SNPs) on 15q14 and 5 SNPs on 15q25 using linear regression analysis with spherical equivalent as a quantitative outcome, adjusted for age and sex. We calculated the odds ratio (OR) of myopia versus hyperopia for carriers of the top-SNP alleles using a fixed effects meta-analysis. At locus 15q14, all SNPs were significantly replicated, with the lowest P value 3.87?×?10(-12) for SNP rs634990 in Caucasians, and 9.65?×?10(-4) for rs8032019 in Asians. The overall meta-analysis provided P value 9.20?×?10(-23) for the top SNP rs634990. The risk of myopia versus hyperopia was OR 1.88 (95?% CI 1.64, 2.16, P?相似文献