Genetic risk sum score comprised of common polygenic variation is associated with body mass index.
Genetic risk sum score comprised of common polygenic variation is associated with body mass index.
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DOI：
10.1007/s00439-010-0917-1
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发表时间：
2011-02
期刊：
影响因子：
5.3
通讯作者：
Webb BT
中科院分区：
文献类型：
--
作者：
Peterson RE;Maes HH;Holmans P;Sanders AR;Levinson DF;Shi J;Kendler KS;Gejman PV;Webb BT
使用大样本进行的体重指数（BMI）全基因组关联研究（GWAS）已经产生了大约十几个强有力的相关变体，并涉及其他位点。这些变量单独的影响很小，总体上解释了一小部分方差。因此，即使有几千个受试者，复制尝试也无法实现全基因组意义。由于先前有强有力的证据表明特定变体对BMI的遗传影响，因此可以应用替代的复制方法。代替按顺序测试单个基因座，可以测试汇总风险等位基因总数的遗传风险总和评分（GRSS）。在目前的研究中，GRSS包括从两个大型荟萃分析中编目的56个顶级变体，在精神分裂症对照的分子遗传学中测试了与BMI的关联（2，653名欧洲裔美国人，973名非洲裔美国人）。在考虑了已知影响BMI的协变量（血统、性别、年龄）后，GRSS与BMI高度相关（p值= 3.19E-06），尽管解释了有限的方差（0.66%）。然而，受试者操作标准曲线下面积（AUC）估计值表明，GRSS和协变量显著预测超重和肥胖分类，具有预测III类肥胖的最大区分能力（AUC = 0.697）。事后检查了各个基因座对GRSS的相对贡献，结果不是由于少数高度显著的变体，而是由于许多影响小的变体。这项研究提供了证据的效用的GRSS作为一种替代方法复制常见的多基因变异的复杂性状。
Genome-wide association studies (GWAS) of body mass index (BMI) using large samples have yielded approximately a dozen robustly associated variants and implicated additional loci. Individually these variants have small effects and in aggregate explain a small proportion of the variance. As a result, replication attempts have limited power to achieve genome-wide significance, even with several thousand subjects. Since there is strong prior evidence for genetic influence on BMI for specific variants, alternative approaches to replication can be applied. Instead of testing individual loci sequentially, a genetic risk sum score (GRSS) summarizing the total number of risk alleles can be tested. In the current study, GRSS comprising 56 top variants catalogued from two large meta-analyses was tested for association with BMI in the Molecular Genetics of Schizophrenia controls (2,653 European-Americans, 973 African-Americans). After accounting for covariates known to influence BMI (ancestry, sex, age), GRSS was highly associated with BMI (p value = 3.19E−06) although explained a limited amount of the variance (0.66%). However, area under receiver operator criteria curve (AUC) estimates indicated that the GRSS and covariates significantly predicted overweight and obesity classification with maximum discriminative ability for predicting class III obesity (AUC = 0.697). The relative contributions of the individual loci to GRSS were examined post hoc and the results were not due to a few highly significant variants, but rather the result of numerous variants of small effect. This study provides evidence of the utility of a GRSS as an alternative approach to replication of common polygenic variation in complex traits.
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DOI：
10.1097/00005768-199911001-00008
发表时间：
1999-11-01
期刊：
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
影响因子：
--
作者：
Jebb, SA;Moore, MS
通讯作者：
Moore, MS
影响因子：
3
作者：
Chen, AS;Metzger, JM;Van der Ploeg, LHT
通讯作者：
Van der Ploeg, LHT
影响因子：
6.9
作者：
Blakemore, Alexandra I. F.;Meyre, David;Walley, Andrew J.
通讯作者：
Walley, Andrew J.
影响因子：
30.8
作者：
Chambers, John C.;Elliott, Paul;Kooner, Jaspal S.
通讯作者：
Kooner, Jaspal S.
影响因子：
5.8
作者：
Johnson, Andrew D.;Handsaker, Robert E.;de Bakker, Paul I. W.
通讯作者：
de Bakker, Paul I. W.