Prediction model for prevalence and incidence of advanced age-related macular degeneration based on genetic, demographic, and environmental variables.
Prediction model for prevalence and incidence of advanced age-related macular degeneration based on genetic, demographic, and environmental variables.
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DOI：
10.1167/iovs.08-3064
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发表时间：
2009-05
影响因子：
4.4
通讯作者：
Rosner B
中科院分区：
文献类型：
--
作者：
Seddon JM;Reynolds R;Maller J;Fagerness JA;Daly MJ;Rosner B
评估遗传、眼部和环境变量的联合效应，并评估AMD患病率和发病率的预测模型。多中心AMD相关眼病研究（AREDS）的参与者被纳入对1446名个体的前瞻性评估中，其中279名进展为晚期AMD（地图状萎缩或新生血管性疾病），1167名在6.3年的随访期间没有进展。对于普遍的AMD，509例晚期病例与222例对照进行了比较。发病率分析的协变量包括年龄、性别、教育、吸烟、体重指数（BMI）、基线AMD分级和AREDS维生素-矿物质治疗分配。对DNA样本中与AMD相关的5个基因中的6个变体进行了评估。对流行和偶发的晚期AMD进行非条件logistic回归分析。开发了一种算法，并计算了受试者工作特征曲线和C统计量，以评估风险评分区分进展者和非进展者的预测能力。在控制了遗传因素、吸烟、BMI和AREDS治疗后，所有遗传多态性与晚期AMD的患病率独立相关。多变量比值比（OR）为3.5 CFH Y 402 H的（95%置信区间[CI]，1.7-7.1）; 3.7 CFH rs 1410996的（95% CI，1.6 - 8.4）; 25.4（95% CI，8.6 - 75.1），对于LOC 387715 A69 S（ARMS 2）; 0.3 C2 E318 D为0.3（95% CI，0.1- 0.5）; CFB为0.3（95% CI，0.1- 0.5）; C3 R102 G为3.6（95% CI，1.4 - 9.4），将纯合风险/保护基因型与参考基因型进行比较。对于偶发性AMD，在控制基线AMD分级和其他因素后，除CFB外的所有这些变异与进展为晚期AMD显著相关，存在两个风险等位基因的OR为1.8至4.0，保护性等位基因为0.4。在控制所有基因型后，CFH 402 H和处理之间观察到相互作用。吸烟与AMD独立相关，与基因型对AMD风险有倍增联合效应。对于进展为晚期AMD，具有所有变量的全模型的C统计量为0.831。反映先天和后天因素与晚期AMD的患病率和发病率独立相关，具有良好的预测能力。
The joint effects of genetic, ocular, and environmental variables were evaluated and predictive models for prevalence and incidence of AMD were assessed. Participants in the multicenter Age-Related Eye Disease Study (AREDS) were included in a prospective evaluation of 1446 individuals, of which 279 progressed to advanced AMD (geographic atrophy or neovascular disease) and 1167 did not progress during 6.3 years of follow-up. For prevalent AMD, 509 advanced cases were compared with 222 controls. Covariates for the incidence analysis included age, sex, education, smoking, body mass index (BMI), baseline AMD grade, and the AREDS vitamin–mineral treatment assignment. DNA specimens were evaluated for six variants in five genes related to AMD. Unconditional logistic regression analyses were performed for prevalent and incident advanced AMD. An algorithm was developed and receiver operating characteristic curves and C statistics were calculated to assess the predictive ability of risk scores to discriminate progressors from nonprogressors. All genetic polymorphisms were independently related to prevalence of advanced AMD, controlling for genetic factors, smoking, BMI, and AREDS treatment. Multivariate odds ratios (ORs) were 3.5 (95% confidence interval [CI], 1.7–7.1) for CFH Y402H; 3.7 (95% CI, 1.6 – 8.4) for CFH rs1410996; 25.4 (95% CI, 8.6 –75.1) for LOC387715 A69S (ARMS2); 0.3 (95% CI, 0.1– 0.7) for C2 E318D; 0.3 (95% CI, 0.1– 0.5) for CFB; and 3.6 (95% CI, 1.4 –9.4) for C3 R102G, comparing the homozygous risk/protective genotypes to the referent genotypes. For incident AMD, all these variants except CFB were significantly related to progression to advanced AMD, after controlling for baseline AMD grade and other factors, with ORs from 1.8 to 4.0 for presence of two risk alleles and 0.4 for the protective allele. An interaction was seen between CFH402H and treatment, after controlling for all genotypes. Smoking was independently related to AMD, with a multiplicative joint effect with genotype on AMD risk. The C statistic for the full model with all variables was 0.831 for progression to advanced AMD. Factors reflective of nature and nurture are independently related to prevalence and incidence of advanced AMD, with excellent predictive power.
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CFH 和 LOC387715/ARMS2 基因型以及抗氧化剂和锌治疗年龄相关性黄斑变性
影响因子：
13.7
作者：
Klein, Michael L.;Francis, Peter J.;Seddon, Johanna M.
通讯作者：
Seddon, Johanna M.
DOI：
10.1073/pnas.0501536102
发表时间：
2005-05-17
影响因子：
11.1
作者：
Hageman, GS;Anderson, DH;Allikmets, R
通讯作者：
Allikmets, R
影响因子：
120.7
作者：
Seddon, JM;Willett, WC;Hankinson, SE
通讯作者：
Hankinson, SE
影响因子：
--
作者：
Kassoff, A;Kassoff, J;Chew, EY
通讯作者：
Chew, EY
影响因子：
56.9
作者：
Edwards, AO;Ritter, R;Farrer, LA
通讯作者：
Farrer, LA