Genome-wide linkage screen for stature and body mass index in 3.032 families: evidence for sex- and population-specific genetic effects.
Genome-wide linkage screen for stature and body mass index in 3.032 families: evidence for sex- and population-specific genetic effects.
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DOI：
10.1038/ejhg.2008.152
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发表时间：
2009-02
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身高(成人身高)和体重指数(BMI)具有很强的遗传成分，可以解释在人类群体中观察到的变异，然而，识别这些遗传成分是极其具有挑战性的。显然，样本量是成功识别构成这些多基因性状遗传结构的数量性状基因座(QTL)的关键决定因素。家庭研究中固有的共享环境和已知的遗传关系为基因图谱研究提供了明显的优势，而不是利用无关的个人进行研究。为此，我们结合了四个先前进行的基于家庭的全基因组筛查的基因型和表型数据，得到了来自3.032个非裔美国人和欧洲裔美国人家庭的9.371个个体的样本，并对身高和体重指数进行了方差成分连锁分析。据我们所知，这项研究是迄今为止发表的关于身高和体重指数的单一最大的基于家族的全基因组连锁扫描。这个大的研究样本让我们也可以进行针对人群和性别的分析。对于身高，我们在11q23、12q12、15q25和18q23以及15q26和19q13上发现了与身高连锁的证据，这些座位以前没有与身高连锁。对于BMI，我们发现了两个基因座的证据：一个在7q35上，另一个在11q22上，这两个基因之前都曾在多个人群中与BMI有关。我们的结果表明，1)合并数据以最大化样本量和2)通过分析可以减少组内差异的子组来最小化异质性的好处，并表明后者可能是在遗传图谱中更成功的方法。
Stature (adult body height), and body mass index (BMI) have a strong genetic component explaining observed variation in human populations, however, identifying those genetic components has been extremely challenging. It seems obvious that sample size is a critical determinant for successful identification of quantitative trait loci (QTL) that underlie the genetic architecture of these polygenic traits. The inherent shared environment and known genetic relationships in family studies provide clear advantages for gene mapping over studies utilizing unrelated individuals. To these ends, we combined the genotype and phenotype data from four previously performed family-based genome-wide screens resulting in a sample of 9.371 individuals from 3.032 African-American and European-American families and performed variance-components linkage analyses for stature and BMI. To our knowledge, this study represents the single largest family-based genome-wide linkage scan published for stature and BMI to date. This large study sample allowed us to pursue population-and sex-specific analyses as well. For stature we found evidence for linkage in previously reported loci on 11q23, 12q12, 15q25 and 18q23 as well as 15q26 and 19q13 which have not been linked to stature previously. For BMI we found evidence for two loci: one on 7q35 and another on 11q22 both of which have been previously linked to BMI in multiple populations. Our results show both the benefit of 1) combining data to maximize the sample size and 2) minimizing heterogeneity by analyzing subgroups where within-group variation can be reduced and suggest that the latter may be a more successful approach in genetic mapping.
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发表时间：
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期刊：
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影响因子：
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通讯作者：
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