Linkage Disequilibrium in Wild and Cultured Populations of Pacific Oyster(Crassostrea gigas)

Linkage disequilibrium(LD) can be applied for mapping the actual genes responsible for variation of economically important traits through association mapping.The feasibility and efficacy of association studies are strongly dependent on the extent of LD which determines the number and density of markers in the studied population,as well as the experimental design for an association analysis.In this study,we first characterized the extent of LD in a wild population and a cultured mass-selected line of Pacific oyster(Crassostrea gigas).A total of 88 wild and 96 cultured individuals were selected to assess the level of genome-wide LD with 53 microsatellites,respectively.For syntenic marker pairs,no significant association was observed in the wild population;however,three significant associations occurred in the cultured population,and the significant LD extended up to 12.7 c M,indicating that strong artificial selection is a key force for substantial increase of genome-wide LD in cultured population.The difference of LD between wild and cultured populations showed that association studies in Pacific oyster can be achieved with reasonable marker densities at a relatively low cost by choosing an association mapping population.Furthermore,the frequent occurrence of LD between non-syntenic loci and rare alleles encourages the joint application of linkage analysis and LD mapping when mapping genes in oyster.The information on the linkage disequilibrium in the cultured population is useful for future association mapping in oyster.

Single Nucleotide Polymorphisms (SNPs) Discovery and Linkage Disequilib-rium (LD) in Forest Trees

With completion of the Populus genome sequencing project and the availability of many expressed sequence tags （ESTs） databases in forest trees, attention is now rapidly shifting towards the study of individual genetic variation in natural populations. The most abundant form of genetic variation in many eukaryotic species is represented by single nucleotide polymorphisms （SNPs）, which can account for heritable inter-individual differences in complex phenotypes. Unlike humans, the linkage disequilibrium （LD） rapidly decays within candidate genes in forest trees. Thus, SNPs-based candidate gene association studies are considered to be a most effective approach to dissect the complex quantitative traits in forest trees. The present study demonstrates that LD mapping can be used to identify alleles associated with quantitative traits and suggests that this new approach could be particularly useful for performing breeding programs in forest trees. In this review, we will describe the fundamentals, patterns of SNPs distribution and frequency, summarize recent advances in SNPs discovery and LD and comment on the application of LD in the dissection of complex quantitative traits in forest tress. We also put forward the outlook for future SNPs-based association analysis of quantitative traits in forest trees.

SHEsis,a powerful software platform for analyses of linkage disequilibrium,haplotype construction,and genetic association at polymorphism loci

In multiloci-based genetic association studies of complex diseases, a powerful and high efficient tool for analyses oflinkage disequilibrium (LD) between markers, haplotype distributions and many chi-square/p values with a large numberof samples has been sought for long. In order to achieve the goal of obtaining meaningful results directly from raw data,we developed a robust and user-friendly software platform with a series of tools for analysis in association study withhigh efficiency. The platform has been well evaluated by several sets of real data.

Identification of powdery mildew resistance loci in wheat by integrating genome-wide association study(GWAS) and linkage mapping

Wheat powdery mildew(Blumeria graminis f.sp.tritici, Bgt) is a disease of increasing importance globally due to the adoption of high yielding varieties and modern sustainable farming technologies.Growing resistant cultivars is a preferred approach to managing this disease, and novel powdery mildew resistance genes are urgently needed for new cultivar development.A genome-wide association study was performed on a panel of 1292 wheat landraces and historical cultivars using 5011 single nucleotide polymorphism(SNP)markers.The association panel was evaluated for reactions to three Bgt inoculants, OKS(14)-B-3-1, OKS(14)-C-2-1, and Bgt15.Linkage disequilibrum(LD) analysis indicated that genome-wide LD decayed to 0.1 at 23 Mb, and population structure analysis revealed seven subgroups in the panel.Association analysis using a mixed linear model(MLM) identified three loci for powdery mildew resistance on chromosome 2 B, designated QPm.stars-2BL1,QPm.stars-2BL2, and QPm.stars-2BL3.To evaluate the efficacy of GWAS in gene discovery,QPm.stars-2BL2 was validated using F2 and F2:3 populations derived from PI420646 × OK1059060-126135-3.Linkage analysis delimited the powdery mildew resistance gene in PI 420646 to an interval where QPm.stars-2BL2 was located, lending credence to the GWAS results.QPm.stars-2BL1 and QPm.stars-2BL3, which were associated with four SNPs located at 457.7–461.7 Mb and two SNPs located at 696.6–715.9 Mb in the Chinese Spring reference IWGSC RefSeq v1.0, respectively, are likely novel loci for powdery mildew resistance and can be used in wheat breeding to improve powdery mildew resistance.

An approach to incorporate linkage disequilibrium structure into genomic association analysis

In this study, we propose to use the principal component analysis （PCA） and regression model to incorporate linkage disequilibrium （LD） in genomic association data analysis. To accommodate LD in genomic data and reduce multiple testing, we suggest performing PCA and extracting the PCA score to capture the variation of genomic data, after which regression analysis is used to assess the association of the disease with the principal component score. An empirical analysis result shows that both genotype-based correlation matrix and haplotype-based LD matrix can produce similar results for PCA. Principal component score seems to be more powerful in detecting genetic association because the principal component score is quantitatively measured and may be able to capture the effect of multiple loci.

Distribution Characteristics and Linkage Disequilibrium of TIM4 Promoter Polymorphisms in Asthma Patients of Chinese Han Population

To investigate the distribution characteristics and linkage disequilibrium of T cell immunoglobulin domain and mucin domain protein 4 （TIM4） promoter polymorphisms in asthma patients of Chinese Han population, the promoter region of TIM4 was re-sequenced by PCR-sequencing, and linkage disequilibrium was analyzed by SHEsis software. Four single nucleotide polymor- phisms （SNPs） in the promoter region of TIM4 were detected, including two new SNPs （at positions -1609, -153） and two reported SNPs （rs6874202, rs6882076）. The frequency distribution of rs6882076 was different among different races （P〈0.05）. In addition, linkage disequilibrium among the SNPs of the promoter region of TIM4 was found and GGTG was the predominant haplotype. There were four SNPs in the promoter region of TIM4 in asthma patients of Chinese Han population, which were in linkage disequilibrium.

Detection of QTL(quantitative trait loci) associated with wood density by evaluating genetic structure and linkage disequilibrium of teak

To find the quantitative trait loci associated with wood density in teak(Tectona grandis L.f.), 21 co-dominant markers including 13 site specific recombinase and 8 EST-based co-dominant markers designed from lignin biosynthesis genes were applied to 174 teak plus tree clones at the National Germplasm Bank, Chandrapur,India. The germplasm bank exhibited 10.6% coefficient of variation for wood densities with 84.5 ± 31.3 genetic polymorphism(%). The highly panmictic set of genotypes(FST= 0.035 ± 0.004) harbored 96.47 ± 0.40 genetic variability(%). The average allelic frequency of the 21 codominant markers was 0.65 ± 0.11 with 12.9% pairs of loci in significant LD(p\0.05, R^2 values [ 0.1), confirming their suitability for a strong marker-trait association study. The marker CCoAMT-1 was significantly(p\0.01) associated with wood density showing stability by both GLM and MLM models and explained 4.3% of the phenotypic effect. The marker from the EST representing CCoAMT can be further developed for gene-assisted selection of elite genotypes of teak with greater wood density. Therefore, we believe that the report will help accelerate the genetic improvement and advance the breeding program of the species.

Haplotype phasing after joint estimation of recombination and linkage disequilibrium in breeding populations

A novel method for haplotype phasing in families after joint estimation of recombination fraction and linkage disequilibrium is developed. Results from Monte Carlo computer simulations show that the newly developed E.M. algorithm is accurate if true recombination fraction is 0 even for single families of relatively small sizes. Estimates of recombination fraction and linkage disequilibrium were 0.00 （SD 0.00） and 0.19 （SD 0.03） for simulated recombination fraction and linkage disequilibrium of 0.00 and 0.20, respectively. A genome fragmentation phasing strategy was developed and used for phasing haplotypes in a sire and 36 progeny using the 50 k Illumina BeadChip by： a） estimation of the recombination fraction and LD in consecutive SNPs using family information, b） linkage analyses between fragments, c） phasing of haplotypes in parents and progeny and in following generations. Homozygous SNPs in progeny allowed determination of paternal fragment inheritance, and deduction of SNP sequence information of haplotypes from dams. The strategy also allowed detection of genotyping errors. A total of 613 recombination events were detected after linkage analysis was carried out between fragments. Hot and cold spots were identified at the individual （sire level）. SNPs for which the sire and calf were heterozygotes became informative （over 90%） after the phasing of haplotypes. Average of regions of identity between half-sibs when comparing its maternal inherited haplotypes （with at least 20 SNP） in common was 0.11 with a maximum of 0.29 and a minimum of 0.05. A Monte-Carlo simulation of BTA1 with the same linkage disequilibrium structure and genetic linkage as the cattle family yielded a 99.98 and 99.94% of correct phases for informative SNPs in sire and calves, respectively.

Testing for Homogeneity of Linkage Disequilibrium Across Strata

In this article, using the likelihood score theory extended to nuisance parameters we derive a new homogeneity score test for comparing linkage disequilibrium across several strata. Power and sample size formulae are also obtained.

Use of Observed Genomic Information to Infer Linkage Disequilibrium between Markers and QTLs

Conducting genomic selection in admixed populations is challenging and its accuracy in this case largely depends on the persistence of linkage disequilibrium between single nucleotide polymorphisms (SNP) and quantitative trait loci (QTL). Inferring linkage disequilibrium (LD) between SNP markers and QTLs could be important in understanding the change of SNP marker effects across different breeds. Predicting the change in linkage disequilibrium between markers and QTLs across two divergent breeds was explored using information from the genotype data. Two different models (M1, M2) that differ in the definition of the explanatory variables were used to infer the level of LD between SNP markers and QTLs using all markers in the panel or windows of fixed number of markers. Three simulation scenarios were conducted using different number of SNPs and QTLs. In the first scenario, the resulting coefficient of determination (R2) was 0.65 and 0.52 using M1 and M2, respectively. In the second scenario, average R2 equaled 0.12 using all markers in the panel and 0.25 using 100 marker windows. Across the three simulation scenarios, it was clear that a significant portion of the variation in the change in LD between SNP markers and QTLs could be explained by information already available in the observed SNP marker data.

Identification of Single Nucleotide Polymorphisms and Analysis of Linkage Disequilibrium in Different Bamboo Species Using the Candidate Gene Approach

Bamboos are one of the most beautiful and useful plants on Earth.The genetic background and population structure of bamboos are well known,which helps accelerate the process of artificial domestication of bamboo.Partial sequences of six genes involved in nitrogen use efficiency in 32 different bamboo species were analyzed for occurrence of single nucleotide polymorphisms(SNPs).The nucleotide diversityθw and total nucleotide polymorphismsπT of the sequenced DNA regions was 0.05137 and 0.03332,respectively.Bothπnonsyn/πsyn and Ka/Ks values were<1.The nucleotide sequences of these six genes were inferred to be relatively conserved,and the haplotype diversity was relatively high.The results of evolutionary neutrality tests showed that the six genes were in line with neutral evolution,and that the NRT2.1 and AMT2.1 gene sequences may have experienced negative selection.An inter-SNP recombination event at the NRT2.1 gene in the all pooled sample,of all 32 bamboo species was the lowest at 0.0645,whereas the AMT gene recombination events were all>0.1.Estimation and analysis of linkage disequilibrium of five genes revealed that with the increase in nucleotide sequence length,the degree of SNP linkage disequilibrium decreased rapidly.We inferred the population genetic structure of 32 bamboo species based on the SNP loci of six genes with frequencies>18%.32 bamboo species were divided into five categories,which indicated that the combined population of all bamboo species had obvious multivariate characteristics and was heterogeneous;red(Group 1)and green(Group 2)were the main groups.

Fine mapping of multiple interacting quantitative trait loci using combined linkage disequilibrium and linkage information

Quantitative trait loci (QTL) and their additive, dominance and epistatic effects play a critical role in complex trait variation. It is often infeasible to detect multiple interacting QTL due to main effects often being confounded by interaction effects. Positioning interacting QTL within a small region is even more difficult. We present a variance component approach nested in an empirical Bayesian method, which simultaneously takes into account additive, dominance and epistatic effects due to multiple interacting QTL. The covariance structure used in the variance component approach is based on combined linkage disequilibrium and linkage (LDL) information. In a simulation study where there are complex epistatic interactions between QTL, it is possible to simultaneously fine map interacting QTL using the proposed approach. The present method combined with LDL information can efficiently detect QTL and their dominance and epistatic effects, making it possible to simultaneously fine map main and epistatic QTL.

Whole-population Mapping of Sugarcane Germplasm Using Linkage Disequilibrium

Commercially grown sugarcane cultivars are advanced generation hybrids between two polyploid ancestor species, S. off icinarum L. (x=10, 2n=8x=80) and S. spontaneum (x= 8, 2n=5-16x=40-128). Modern cultivars

鸡FGF6基因生物学特性及其多态性与经济性状的关联分析

旨在探究鸡成纤维细胞生长因子6(fibroblast growth factor 6,FGF6)基因的生物学特性,挖掘FGF6基因单核苷酸多态性(SNP)位点并分析其与经济性状的相关性,为后续研究鸡FGF6基因对生长性状的影响提供参考。本研究对FGF6蛋白序列进行生物信息学分析;基于768只固始鸡-安卡鸡F_2资源群的GBS数据及相关经济性状表型数据对FGF6基因包含启动子2 kb区域SNP位点进行筛选,并进行连锁不平衡和关联分析,探究FGF6基因SNP和单倍型与鸡经济性状的相关性。生物信息学分析结果显示,鸡FGF6氨基酸序列与火鸡同源性为91.26%;系统进化分析表明,鸡FGF6与火鸡亲缘关系最近,其次是绿海龟,与斑马鱼遗传距离最远;保守性分析显示不同物种间FGF6保守性较高。鸡FGF6蛋白为亲水性蛋白、存在1个跨膜区,主要定位于细胞质;其二级、三级结构相符。鸡FGF6蛋白被22个磷酸化位点和1个N-糖基化位点修饰;与其受体家族FGFR1~4和EGF存在互作关系。鸡FGF6基因启动子区域筛选到6个SNPs位点,均位于1号内含子上;多态性分析显示6个SNPs位点存在高多态性,其中5个处于哈代-温伯格平衡,呈强连锁状态(D′=1,r^(2)=1)。关联分析结果显示,rs73399071位点与F_2资源群不同阶段体重(BW)、胫长(SL)、胫围(SG)、体斜长(BSL)等17个生长性状指标显著相关(P<0.05),与全净膛重(EW)、半净膛重(SEW)、屠体重(CW)、胸肌重(BMW)等10个屠体性状指标显著相关(P<0.05),与肉质性状的关联未达到显著水平(P>0.05),与高密度脂蛋白(HDL)和胆碱酯酶(ChE)显著相关(P<0.05),CC基因型个体的大部分性状表型均值高于GG基因型个体;单倍型组合分析显示不同阶段CCTTCCTTCC组合个体的体重均高于其他单倍型组合个体。本研究结果为进一步探究鸡FGF6基因的功能提供理论参考,筛选到FGF6基因存在5个与固始鸡-安卡鸡F_2资源群体重、体尺、屠体性状和血液生化指标显著关联的SNPs位点,为鸡育种提供候选的分子标记,为地方鸡标记辅助选择提供新的思路。

LD-PCR检测FⅧ基因XbaⅠ位点多态性及其在血友病A携带者诊断中的应用

目的建立高特异性的针对凝血因子Ⅷ(FⅧ)基因内含子22中XbaⅠ多态性位点的连锁分析法,以用于血友病A家系携带者的诊断。方法采用长距离PCR(LD-PCR)方法,特异性地扩增FⅧ基因内含子22中的XbaⅠ位点所在区域,用限制性内切酶XbaⅠ酶切,对5个血友病A家系作家系连锁分析,并对其中可提供多态性信息的家系作携带者诊断。结果家系1中确诊女性携带者1名及1名正常女性成员;家系2中确诊1名女性携带者;而家系3、家系4和家系5该位点无法提供多态性信息。结论基于LD-PCR的FⅧ基因XbaⅠ位点连锁分析方法具有较高的准确性和可靠性,这对临床上诊断血友病A携带者具有积极的意义。

白细胞介素1B基因连锁不平衡与原发性冻结肩的易感性

背景:国内外大量文献证实白细胞介素1β的升高与原发性冻结肩相关,白细胞介素1B(IL-1B)基因多态性能够影响白细胞介素1β相关基因的转录及蛋白表达,使得体内细胞因子水平发生改变,从而改变原发性冻结肩的发生率。拟通过对白细胞介素1B基因多态性与原发性冻结肩易感性的研究,从分子生物学角度为原发性冻结肩的发病机制探索新的突破口,寻找原发性冻结肩的易感基因。目的:探索白细胞介素1B基因中3个基因位点连锁不平衡与原发性冻结肩易感性的关联性。方法:采用病例对照研究,将研究对象分为2组,一组为184例原发性冻结肩患者,另一组为260名健康对照人群。通过聚合酶链反应和限制性片段长度多态性方法检测两组白细胞介素1B基因位点-511C/T(rs16944)、+3954C/T(rs1143634)和-31C/T(rs1143627)的基因型,并比较分析这3个位点连锁不平衡概率以及形成单倍体与原发性冻结肩患病风险率之间的相关性。结果与结论:经非条件Logistic回归分析发现,在原发性冻结肩中rs1143634位点和rs1143627位点CT基因型比例明显增加且差异有显著性意义;连锁不平衡分析显示对照组中rs16944、rs1143634、rs1143627位点趋于平衡(D’值<0.1),而原发性冻结肩组中rs1143627与rs1143634位点之间存在一定程度上的连锁不平衡(D’值=0.595);单倍体型TTT相较于CCT型可使得原发性冻结肩风险增加6.66倍(TTT,OR=6.66,95%CI=1.59-27.88,P=0.0097)。结果表明,在原发性冻结肩患者中白细胞介素1B基因rs1143627与rs1143634位点之间存在一定程度上的连锁不平衡;由3个基因位点形成的单倍体型TTT可能会增加罹患原发性冻结肩的风险。

一种快速挖掘鸡品种特征性SNP标记集合的方法

旨在建立一种快速挖掘鸡品种/品系特征性SNP标记集合的方法,实现通过少量SNP标记将目标品种/品系与其他品种/品系区分的目标。本研究以北京油鸡、京星黄鸡、7个山东地方鸡种、5个云南地方品种、藏鸡和白羽肉鸡专门化品系等19个品种/品系全基因组重测序数据为素材,通过群体分化指数分析后,提取MEAN_FAST≥0.65的SNP标记,进一步通过连锁不平衡分析提取独立SNP来缩减特征性SNP标记集合。随机选择6个品种/品系对该方法进行检验,结果表明,通过一次群体分化指数和连锁不平衡分析后进行位点筛选后,即可分别获得白羽肉鸡品系、京星黄鸡H系和京星黄鸡D2系的114、220和226个特征性SNPs位点,将目标品系与其它共18个代表性品种分开。对于在主成分和聚类分析中聚集在同一个分支的武定鸡和瓢鸡,通过该方法可分别获得204和178个特征性SNPs标记,将之与其它代表性品种分开。综上,通过本方法,可得到目标品种114~226个SNPs标记构成的集合,进一步利用主成分分析即可将目标品种/品系与其它代表性品种进行区分。该方法流程简便,获得的特征性SNP标记相对较少,有利于控制检测成本,可应用于地方品种或商业化品系的“分子身份证”构建,辅助种质资源保护和鉴定工作。

利用高密度SNP芯片评估中国地方肉牛品种基因组亲缘关系

旨在在系统对比分析亲缘关系不同计算方法基础上探索适合我国肉牛地方品种的亲缘关系评估方法。本研究主要以柴达木牛等10个肉牛地方品种为研究对象,使用重抽样方法获得地方品种的模拟数据,以此为基础使用PCA聚类结果为参照,分别利用预测误差方差、广义决定系数、预测误差相关系数及SNP与QTL的连锁一致性程度系统对比了不同评估方法对地方品种亲缘关系的分类结果,并探索了遗传力因素对不同亲缘关系评估方法的影响。通过PCA分析可知10个肉牛地方品种可分为3大类,分别为北方牛品种(柴达木牛、西藏牛、蒙古牛以及延黄牛)、南方牛品种(文山牛、南丹牛以及雷琼牛)和西南牛品种(平武牛、凉山牛以及昭通牛),该分类结果与上述品种地理分布较为一致。与PCA结果对比发现,基于LD一致性的亲缘关系评估方法的评估结果与PCA聚类结果一致,且该方法能够使用皮尔逊相关系数量化品种间亲缘关系,具有较好的准确性。PEVD法、CD法与r法3种方法与上述方法相比评估群体间亲缘关系时容易受到性状估计育种值的误差方差影响,从而造成种间亲缘关系评估结果出现误差。评估结果影响因素分析发现,PEVD法、CD法和r法与PCA和LD一致性评估法相比,易受到评估性状遗传力的影响,评估结果稳定较差。而PCA和LD一致性评估法由于仅依赖基因组数据,不受到遗传力影响,能够更稳定的量化评估品种间亲缘关系,具有更好的可靠性。因此,基于LD一致性评估方法结果可准确量化评估肉牛品种间亲缘关系且评估结果稳定性较高。

不同筛选方法的低密度SNP集合填充准确性比较

【目的】尝试通过在华西牛参考群高密度标记芯片位点中,使用两种标记筛选方法挑选具有代表性的且密度梯度不同的SNP位点集合,后利用基因组填充策略在相同填充参数下将低密度芯片数据填充至高密度继而进行后续基因组研究,从而达到降低华西牛基因型分型成本的目的。研究分别比较了不同标记集合填充准确性和填充一致性的差异,阐述了标记筛选方法、标记密度、最小等位基因频率和参考群体数量等4个因素对填充结果的影响,为华西牛低密度SNP填充芯片设计提供参考。【方法】将质控后剩余的1233头华西牛群体随机分为参考群(986头)和验证群(247头)。使用等间距法(equidistance,EQ)和高MAF法(high MAF,HM)两种标记筛选方法分别从华西牛参考群体的Illumina Bovine HD芯片位点集合中筛选出16种不同密度的SNP集合,共生成32种不同SNP梯度密度集合。随后在验证群体中利用Beagle(v5.1)软件将各低密度集合填充至770 k密度水平,计算填充准确性和填充一致性并对填充性能影响因素进行分析。【结果】32种低密度SNP集合的标记数量在100—16000之间,窗口最大为24176 kb,最小151 kb。随着标记密度升高,EQ和HM两种筛选方法填充一致性和准确性不断提升,但填充准确性和填充一致性增加的幅度越来越小。当标记集合密度超过12 k后均趋于平稳。SNP密度在16 k时两种方法的填充准确性达到最高(r^(2)_(EQ)=0.8801,r^(2)_(MAF)=0.8696)。当标记密度低于11 k时,不同标记密度梯度下HM方法填充一致性均高于EQ方法。然而当SNP集合密度超过11 k时,EQ筛选方法较表现出填充优势。与填充一致性结果趋势相似,在SNP集合密度低于10 k时,HM方法仍然具有较高的填充准确性,但当SNP集合密度高于10 k时,EQ方法的填充准确性则较高,且在SNP密度集合大于12 k后,EQ填充准确性趋于稳定。同时研究发现与低MAF标记位点相比,高MAF位点的填充准确性更高。填充过程中发现,填充一致性和填充准确性随着参考群体增大而提高。当参考群体数量在600—800时,位点填充准确性和一致性较高。【结论】在华西牛群体中,填充一致性和填充准确性随标记密度递增而上升,在标记密度为10 k—12 k区间,可获得较好的填充效果。当标记密度小于10 k时优先选择HM方法,更高密度时EQ方法较好。高MAF标记位点填充准确性更高。采用填充策略进行低密度标记填充时,参考群体数量在400头以上时填充效果较为理想。

TMTC1基因多态性与精神分裂症的关联性

目的探讨TMTC1基因单核苷酸多态性与精神分裂症的相关性。方法共纳入207例精神分裂症患者和186例健康对照。采用SNPscan TM多重SNP分型技术,对TMTC1基因7个SNP位点进行基因分型检测,比较等位基因、基因型和单倍型之间的差异,并分析在不同的遗传模式下SNP位点与精神分裂症易感性的相关性。结果7个SNP位点的基因型分布均符合Hardy-Weinberg平衡;7个位点的等位基因频率和基因型频率分布在2组间差异无统计学意义(P>0.05)。不同遗传模式下7个SNP位点多态性均与精神分裂症发病风险无关(P>0.05);但rs10332与rs16934358、rs10332与rs2023588、rs16934358与rs2023588、rs16934358与rs7503之间存在高度连锁不平衡。结论TMTC1基因rs7503、rs10332、rs2023588、rs16934358、rs2113879、rs679087、rs4931240位点多态性与精神分裂症无关,需要扩大样本量和筛选新的SNP位点进一步分析。