Common SNPs explain a large proportion of the heritability for human height.
Common SNPs explain a large proportion of the heritability for human height.
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全基因组关联研究 (GWAS) 发现的单核苷酸多态性 (SNP) 仅占人类复杂性状遗传变异的一小部分。剩下的遗传力在哪里？我们使用线性模型分析估计了由 3,925 个无关个体基因分型的 294,831 个 SNP 所解释的人类身高方差的比例，并通过基于观察到的基因型数据的模拟验证了估计方法。我们表明，45% 的方差可以通过同时考虑所有 SNP 来解释。因此，大部分遗传力并未缺失，而是之前未被检测到，因为个体效应太小而无法通过严格的显着性检验。我们提供的证据表明，剩余的遗传力是由于因果变异和基因分型 SNP 之间的不完全连锁不平衡 (LD) 造成的，而次要等位基因频率 (MAF) 低于迄今为止探索的 SNP 的因果变异加剧了这种不平衡。
Single nucleotide polymorphisms (SNPs) discovered by genome-wide association studies (GWASs) account for only a small fraction of the genetic variation of complex traits in human populations. Where is the remaining heritability? We estimated the proportion of variance for human height explained by 294,831 SNPs genotyped on 3,925 unrelated individuals using a linear model analysis, and validated the estimation method by simulations based upon the observed genotype data. We show that 45% of variance can be explained by considering all SNPs simultaneously. Thus, most of the heritability is not missing but has not previously been detected because the individual effects are too small to pass stringent significance tests. We provide evidence that the remaining heritability is due to incomplete linkage disequilibrium (LD) between causal variants and genotyped SNPs, exacerbated by causal variants having lower minor allele frequency (MAF) than the SNPs explored to date.
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DOI：
10.1375/twin.6.5.399
发表时间：
2003-10-01
期刊：
TWIN RESEARCH
影响因子：
--
作者：
Silventoinen, K;Sammalisto, S;Kaprio, J
通讯作者：
Kaprio, J
影响因子：
2.7
作者：
PATTERSON, HD;THOMPSON, R
通讯作者：
THOMPSON, R
影响因子：
5.3
作者：
Macgregor, Stuart;Cornes, Belinda K.;Visscher, Peter M.
通讯作者：
Visscher, Peter M.
DOI：
10.1073/pnas.0903103106
发表时间：
2009-06-09
影响因子：
11.1
作者：
Hindorff, Lucia A.;Sethupathy, Praveen;Manolio, Teri A.
通讯作者：
Manolio, Teri A.
影响因子：
1.5
作者：
Hayes, B. J.;Visscher, P. M.;Goddard, M. E.
通讯作者：
Goddard, M. E.