The genetic dissection of complex traits in a founder population
The genetic dissection of complex traits in a founder population
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DOI：
10.1086/324025
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发表时间：
2001-11-01
影响因子：
9.8
通讯作者：
McPeek, MS
中科院分区：
文献类型：
--
作者：
Ober, C;Abney, M;McPeek, MS
我们估计了广义遗传力（H-2）和狭义遗传力（h（2）），并进行了全基因组筛选，使用一种新的基于关联的作图方法，在哈特人（Hutterites）中定位20个数量性状基因座（QTL），哈特人是一个实践社区生活方式的创始人群体。遗传度估计值从舒张压（DBP）的0.21到全血5-羟色胺水平的0.99不等。使用多点方法检测隐性模型下的关联，我们发现了六个性状的主要QTL的证据：低密度脂蛋白（LDL），甘油三酯，脂蛋白（a）（Lp[ a]），收缩压（SBP），血清皮质醇和全血5-羟色胺。第二个主效QTL Lp（a）和皮质醇使用一个单一的点的方法来检测一般的两个等位基因模型下的关联。这六个性状的遗传力范围从甘油三酯的0.37到血清素的0.99，三个性状（LDL、SBP和血清素）具有显著的显性方差（即，H-2/h（2））。令人惊讶的是，在全基因组筛选中，遗传力的测量值和关联强度之间几乎没有相关性（P> 0.50），这表明遗传力估计本身并不能识别受主要效应基因影响的表型。本研究证明了全基因组关联研究QTL定位的可行性。然而，即使在这个具有广泛连锁不平衡的年轻建立者群体中，也可能需要远小于5cM的图密度来检测所有主要QTL。
We estimated broad heritabilities (H-2) and narrow heritabilities (h(2)) and conducted genomewide screens, using a novel association-based mapping approach for 20 quantitative trait loci (QTLs) among the Hutterites, a founder population that practices a communal lifestyle. Heritability estimates ranged from .21 for diastolic blood pressure (DBP) to .99 for whole-blood serotonin levels. Using a multipoint method to detect association under a recessive model we found evidence of major QTLs for six traits: low-density lipoprotein (LDL), triglycerides, lipoprotein (a) (Lp[ a]), systolic blood pressure (SBP), serum cortisol, and whole-blood serotonin. Second major QTLs for Lp( a) and for cortisol were identified using a single-point method to detect association under a general two-allele model. The heritabilities for these six traits ranged from .37 for triglycerides to .99 for serotonin, and three traits (LDL, SBP, and serotonin) had significant dominance variances (i.e., H-2/h(2)). Surprisingly, there was little correlation between measures of heritability and the strength of association on a genomewide screen (P>.50), suggesting that heritability estimates per se do not identify phenotypes that are influenced by genes with major effects. The present study demonstrates the feasibility of genomewide association studies for QTL mapping. However, even in this young founder population that has extensive linkage disequilibrium, map densities much less than 5 cM may be required to detect all major QTLs.