对数线性模型在病例-父母/对照-母亲混合设计中的应用

以唇腭裂与亚甲基四氢叶酸还原酶(MTHFR)基因A1298C多样性的关系为例,基于似然比检验(LRT)的对数线性模型分析母亲、子代基因型与唇腭裂的关系,介绍应用对数线性模型分析病例-父母/对照-母亲混合设计资料的方法应用。发现母亲基因型为CC时,相对于基因型为AA的母亲,其子代唇腭裂发病风险降低,S₂=0.45(95%CI:0.26~0.79);子代基因型为AC时,相对于AA其发病风险降低,R₁=0.69(95%CI:0.48~0.97),其余未见关联。混合设计的效力要大于病例-父母对照研究(0.86>0.78)。表明MTHFR A1298C可能在唇腭裂的病因学机制中起重要作用。应用对数线性模型对这类混合设计资料的分析可以同时探讨母亲、子代基因型对疾病的影响,且相对病例-父母对照研究效力更高,适用于出生缺陷等生命早期疾病的病因学研究。     

不完全病例对照研究基因环境交互作用的估计

目的 介绍不完全病例对照研究中基因与环境交互作用的估计方法.方法 分别导出了logistic模型、对数线性模型在传统病例对照研究、单纯病例研究、不完全病例对照研究中主效应以及基因与环境交互作用效应的极大似然估计,并通过实例分析其应用价值.结果 在传统病例对照研究中,当数据未缺失时,logistic模型与对数线性模型的结果是等价的.当无对照时,单纯病例研究的logistic模型可以估计基因与环境的交互作用.当对照组基因信息缺失但环境信息齐全时,用传统病例对照研究的logistic模型无法得到交互作用的估计;用单纯病例研究的logistic模型可以估计交互作用,但由于没有充分利用环境的信息,故得不到环境主效应的估计;不完全病例对照研究的对数线性模型,可同时得到交互作用和环境主效应的估计.结论 不完全病例对照研究采用对数线性模型既可充分利用对照的环境暴露信息,估计环境的主效应,又可估计基因与环境的交互作用.当基因与环境暴露独立时,其估计值与完全数据是等价的.     

对数线性模型在骨折资料分析中的应用

目的应用对数线性模型对骨折资料进行分析.方法收集了天津医院1993～2002年的骨折病历资料,采用对数线性模型对上述资料进行分析.结果骨折患者的年龄,性别和骨折原因间存在着交互作用.结论对数线性模型可以更好的分析多个变量间的交互作用,适用于探索性的研究.     

病例对照方法在基因环境交互作用研究中的应用

现代流行病学研究越来越重视基因与环境交互作用，要研究基因环境交互作用，需要有基因型、表现型（患病与否）与环境暴露信息，由于基因型测定需要有尖端技术、设备，而且耗资巨大，不是首选方法，人们往往首先采用替代性方法对研究对象进行基因型分类。病例对照研究是流...     

病例父母对照研究在遗传性疾病中的应用

现代分子生物技术和基因组信息学的发展,使进一步寻找疾病的易感基因成为可能,许多新的统计方法被引入多基因遗传病的研究,如群体关联分析(病例对照研究)、单纯病例研究、病例父母对照研究和患病亲属对研究,这些都是探索疾病的易感基因及研究基因与环境致病因素交互作用常用的研究方法.但是,病例对照研究在选择对照时要求很严格,该方法要求对照的遗传背景一致,而且由于群体的混合等容易造成虚假关联现象;单纯病例研究只能评估环境致病因素和易感基因都存在时的相乘模型交互作用,而不能单独评估易感基因的效应,以及它还存在不同亚人群暴露率和基因频率不一致所引起的偏倚.因此,Fack和Rubinstein提出了病例父母对照研究.     

对数线性模型分析在煤工尘肺生命质量评价中的应用

对数线性模型分析是一种处理复杂列联表资料的重要方法。本文着重介绍了煤工尘肺生命质量评价中的对数线性模型分析结果及专业解释。此方法在探讨因素间交互作用方面比相关回归分析更前进了一步。提供了定量比较的数据，有助于生命质量评价的统计分析工作。     

危险度评价中的非传统病例-对照研究

近年来,复杂性疾病(complex disorder)的致病基因及其与环境的交互作用(interaction)已成为病因学研究的热点问题.病例-对照研究(case-control study)通过比较大量病人与种族相似、无关联的对照中变异等位基因的频率来评估基因、环境,及其交互作用与疾病的关联.由于这种方法易于实施而且对于基因定位非常有用,因而在分析遗传性疾病时发挥了重要的作用.     

不完全病例对照研究中对照组部分基因信息缺失基因-环境交互作用的估计

目的探讨不完全病例对照研究中对照组基因信息部分缺失时基因一环境交互作用的估计。方法在Stata9．0软件上采用MonteCarlo方法模拟不同基因信息缺失比例数据，对缺失数据采用hotdeck多重填补程序后分析和删除缺失值分析结果进行比较。结果缺失数据〈50％时，hotdeck多重填补后分析和删除缺失值分析对环境主效应、基因主效应以及基因-环境交互作用的估计系数接近完全数据的系数，随缺失比例的增加，两种方法的估计方差均增加，但hotdeck多重填补估计方差小于删除缺失值分析。结论不完全病例对照研究中，对照组基因信息缺失比例〈50％时，可以用hotdeck填补方法充分利用已有的信息估计基因-环境的交互作用，提高估计精度。     

配对病例对照研究基因与基因交互作用样本量的确定

目的 采用配对病例对照研究探讨基因与基因交互作用所需的样本量。方法 logistic回归分析原理建立两基因与一种疾病相关性模型,以模拟参数值回代计算样本量,计算过程以QUANTO软件完成。结果(1)基因交互作用越大,所需样本量越少;基因型分布频率P_r为35％(相当于显性遗传模型易感基因频率等于0.20、阴性遗传模型易感基因频率等于0.60)时,基因交互作用的样本量最少:如两基因主作用均为2,基因交互作用为2时样本量为700例;基因交互作用为5时样本量为200例。(2)探讨基因主作用与探讨基因交互作用所需的样本量不同。结论 提供了可供查阅的两基因交互作用样本含量值。     

基因-环境交互作用研究方法:无对照病例研究

从目前的观点来看 ,可以认为很少有疾病是纯粹由遗传或者环境因素决定的 ,基因 环境交互作用在许多疾病 ,特别是常见的慢性疾病或者是所谓的“复杂性状疾病”(ｃｏｍｐｌｅｘ ｔｒａｉｔｄｉｓｅａｓｅｓ)的发病中 ,具有非常重要的意义[1 ] 。基因 环境交互作用可以理解为遗传因素对环境因素易感性的影响[2 ] 。对于基因 环境交互作用的深入研究 ,有助于了解人群易感性差异的原因 ,进而可以对环境与疾病、基因与疾病的关系有更深入的认识。目前许多对复杂性状疾病病因的遗传流行病学研究得到非常不一致的结论[3] ,没有考虑到基因 环境交…     

2 173例骨折住院患儿资料的分析——对数线性模型的应用

目的 了解湖南省骨折住院患儿影响因素间的交互作用,为儿童骨折的防治制定有针对性的措施。方法 采用对数线性模型对儿童骨折影响因素间的交互项进行筛选与分析。结果 不同类型骨折住院患儿的治愈率（（口恶）²=51.036,P<0.001）、住院日（H=67.101,P<0.001）和住院费用（H=46.282,P<0.001）均有统计学差异;骨折住院患儿的骨折原因与骨折类型两者之间存在交互作用,跌落易导致尺桡骨骨折,而交通事故则易出现胫腓骨骨折;骨折住院患儿的性别、年龄与骨折原因三者之间存在交互作用,0~3岁男孩易由交通事故和跌落这两种伤害类型导致骨折;骨折住院患儿的性别、年龄与骨折类型三者之间也存在交互作用,0~3岁儿童,不论男孩女孩,发生尺桡骨骨折和肱骨骨折这两种骨折类型可能性比较低。结论 应根据不同年龄,性别,骨折原因以及骨折类型采取有针对性的措施预防儿童骨折;对数线性模型可以更好的用于分析多个变量间的交互作用,适用于探索性的研究。     

Variants of developmental genes (TGFA,TGFB3, and MSX1) and their associations with orofacial clefts: a case-parent triad analysis

We selected 262 case-parent triads from a population-based study of orofacial clefts in Norway, and examined variants of developmental genes TGFA, TGFB3, and MSX1 in the etiology of orofacial clefts. One hundred seventy-four triads of cleft lip cases (CL+/-P) and 88 triads of cleft palate only cases (CPO) were analyzed. There was little evidence for an association of any of these genes with CL+/-P. The strongest association was a 1.7-fold risk with two copies of the TGFB3-CA variant (95% CI=0.9-3.0). Among CPO cases, there was a 3-fold risk with two copies of the TGFA TaqI A2 allele, and no increase with one copy. Assuming this to be a recessive effect, we estimated a 3.2-fold risk among babies homozygous for the variant (95% CI=1.1-9.2). Furthermore, there was strong evidence of gene-gene interaction. While there was only a weak association of the MSX1-CA variant with CPO, the risk was 9.7-fold (95% CI=2.9-32) among children homozygous for both the MSX1-CA A4 allele and the TGFA A2 allele. No association of CPO with the TGFA variant was seen among the other MSX1-CA genotypes. In conclusion, no strong associations were found between CL+/-P and variants at these three genes. There was a possible recessive effect of the TGFA TaqI variant on the risk of CPO, with a 3-fold risk among children homozygous for the variant. The effect of this TGFA genotype was even stronger among children homozygous for the MSX1-CA A4 allele, raising the possibility of interaction between these two genes.     

Assessing maternal genetic associations: a comparison of the log-linear approach to case-parent triad data and a case-control approach

BACKGROUND: In utero exposures, including maternal phenotypes, are potential risk factors for both early-onset and adult-onset diseases. Two alternative study designs use maternal genotypes at polymorphic loci as biomarkers of an offspring's in utero exposure: (1) a traditional case-control study with logistic regression analysis, in which cases, controls, and mothers of both types of subjects are genotyped; and (2) a case-parent triad study with log-linear analysis, in which cases and both parents are genotyped. METHODS: We used computer simulations to compare the operating characteristics of the log-linear approach to case-parent triad data and the case-control approach for assessing relative risks (RRs) associated with maternal genotypes. RESULTS: For high-risk allele frequencies (chromosomal prevalence; f) between 0.20 and 0.75, both methods allowed for valid, unbiased estimates of maternal RRs. The case-parent triad approach, however, had 43% greater power, on average, than the case-control approach with an equal number of genotypes, and 13% greater power with an equal number of cases. For example, under dominant inheritance, to detect 2-fold maternal RRs with 200 (or 150) cases when allele prevalence is between 0.15 and 0.40, the case-parent triad and equal-genotype case-control designs had, on average, 87% and 62% power, respectively. As f approached 0 or 1, the power of both methods decreased sharply. DISCUSSION: The greater efficiency of case-parent triads may be due to the inclusion of paternal genotype information, which allows for independent tests of disease association with maternal or offspring genotypes. These results highlight one potential advantage of case-parent triad data in assessing maternal genetics as risk factors for offspring disease. We discuss these findings and other considerations between the 2 methodological approaches.     

Improved association analyses of disease subtypes in case-parent triads

The sampling of case-parent triads is an appealing strategy for conducting association analyses of complex diseases. In certain situations, one may have interest in using the triads to identify genetic variants that are associated with a specific subtype of disease, perhaps related to a characteristic cluster of symptoms. A straightforward strategy for conducting such a subtype analysis would be to analyze only those triads with the subtype of interest. While such a strategy is valid, we show that triads without the subtype of interest can provide additional genetic information that increases power to detect association with the subtype of interest. We incorporate this additional information using a likelihood-based framework that permits flexible modeling and estimation of allelic effects on disease subtypes and also allows for missing parental data. Using simulated data under a variety of genetic models, we show that our proposed association test consistently outperforms association tests that only analyze triads with the subtype of interest. We also apply our method to a triad study of attention-deficit hyperactivity disorder and identify a genetic variant in the dopamine transporter gene that is associated with a subtype characterized by extreme levels of both inattentive and hyperactive-impulsive symptoms.     

Performance of the log-linear approach to case-parent triad data for assessing maternal genetic associations with offspring disease: type I error, power, and bias

Maternal genetic variation may serve as a biomarker in studies aimed at clarifying fetal determinants of infant or adult disease. The log-linear approach to case-parent triad data (LCPT) can be used to investigate maternal genetic polymorphisms in relation to offspring disease risk, but LCPT operating characteristics have been reported for only a limited range of situations. The authors performed a simulation study to investigate the performance of the LCPT for assessing maternal associations with offspring disease risk over a wide range of scenarios with varying sample sizes (n), high-risk allele frequencies (f ), and modes of inheritance, all of which greatly affect the expected number of triads in informative categories. For most f values less than 0.5, the LCPT approach with 200 triads allowed for approximately 80% power to detect valid, unbiased maternal relative risks of 2 when inheritance was log-additive or dominant. When inheritance was recessive, this was true for most f 's greater than 0.35. Outside of this range, however, power and bias depended greatly on the mode of inheritance, f, and n. On the basis of these findings, epidemiologists may consider the LCPT a useful approach for assessing maternal relative risks unless one expects a very rare or fairly common maternal allele to increase offspring disease risk.     

Cleft palate, transforming growth factor alpha gene variants, and maternal exposures: assessing gene-environment interactions in case-parent triads

We have previously reported a threefold risk of cleft palate only (CPO) among children homozygous for the less common allele A2 at the TaqI marker site of the transforming growth factor alpha gene (TGFA) (Jugessur et al. [2003a] Genet. Epidemiol. 24:230-239). Here we assess possible interaction between the child's TGFA TaqI A2A2 genotype and maternal cigarette smoking, alcohol consumption, use of multivitamins and folic acid. This was done by comparing the strength of genetic associations between strata of exposed and unexposed case-parent triads. We also looked for possible gene-gene interaction with the polymorphic variant C677T of the folic acid-metabolizing gene MTHFR. We analyzed a total of 88 complete CPO triads selected from a population-based study of orofacial clefts in Norway (May 1996-1998). No evidence of interaction was observed with either smoking or alcohol use. The risk associated with two copies of the A2 allele at TGFA TaqI was strong among children whose mothers did not use folic acid (relative risk=4.5, 95% confidence interval=1.3-15.7), and was only marginal among children whose mothers reported using folic acid (RR=1.4, 95% CI=0.2-12.7). Although the interaction between the child's genotypes at TGFA TaqI and MTHFR-C677T was not statistically significant, the effect of the TGFA TaqI A2A2 genotype appeared to be stronger among children with either one or two copies of the T-allele at C677T (RR=4.0, 95% CI=1.1-13.9) compared to children homozygous for the C-allele (RR=1.7, 95% CI=0.2-15.7). In conclusion, we find little evidence of interaction between the child's genotypes at TGFA TaqI and various exposures for cleft palate, with the possible exception of folic acid intake.     

三联药液治疗压疮的观察及护理

目的结合临床护理经验,就胰岛素、碘伏、抗生素三联药液在压疮患者治疗中的临床应用进行探讨。方法50例压疮患者中,对25例患者采用胰岛素、碘伏、抗生素三联药液的方法进行治疗,25例患者采用其它综合方法治疗。结果25例采用三联药液治疗的患者中,17例患者治愈,5例患者显效,3例患者有效,0例患者无效。25例采用其它综合方法治疗的患者中,9例压疮患者治愈,8例患者显效,4例患者有效,4例患者无效。实验组和对照组的总有效率无差异（P〉0．05）,但两组治愈率和显效率比较有统计学意义（P〈0．01）。两组的愈合时间及指数比较有统计学意义（P〈0．01）。结论胰岛素、碘伏、抗生素三联药液治疗压疮较其它综合方法治疗简捷方便、价格佰官确得了明晶的特娶     

高血压健康危险因素的logistic回归和对数线性模型分析

目的 了解南通市居民高血压危险因素,以期为高血压的早期防治、制定干预措施提供科学依据.方法 采用多级分层随机抽样的方法,抽取南通市6个街道和6个乡镇15岁及以上常住5年以上的自然人群作为调查对象,共调查6 000人,获取有效问卷5 800份.采用SPSS18.0统计软件进行描述性分析、x2检验、logistic回归以及对数线性模型.结果 多元logistic回归与对数线性模型分析结果表明,影响高血压发生的主要危险因素为年龄、高血压家族史、体质指数(BMI)和饮酒.结论 年龄偏大、有高血压家族史、饮酒和高BMI是南通市高血压患病人群的危险因素.