Evidence for three novel QTLs for adiposity on chromosome 2 with epistatic interactions: the NHLBI Family Heart Study.
Evidence for three novel QTLs for adiposity on chromosome 2 with epistatic interactions: the NHLBI Family Heart Study.
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DOI：
10.1038/oby.2009.181
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发表时间：
2009-12
期刊：
影响因子：
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通讯作者：
Borecki IB
中科院分区：
文献类型：
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作者：
Feitosa MF;North KE;Myers RH;Pankow JS;Borecki IB
我们试图通过对体重指数和腰围的全基因组连锁分析来确定数量性状基因座(QTL)，探索解决异质性的各种策略，包括协变量调整和基于上位性方差分量的复杂模型。由于降胆固醇药物和糖尿病药物可能会影响肥胖和冠心病风险，我们排除了治疗高胆固醇和高血糖的受试者。在2p25，连锁的证据增加(BMI：LOD=1.59比2.43，WC：LOD=1.32比2.26)。由于环境和/或遗传因素可以掩盖特定基因座的影响，我们进一步研究了QTL是否可以独立于脂肪途径和饮食习惯影响肥胖。根据Willet的饮食因素和血脂谱，以及调整后的年龄和性别，发现2p25(BMI：LOD=4.31；WC：LOD=4.23)存在连锁的强烈证据。提示血脂谱和饮食习惯是检测2p25肥胖QTL的混杂因素。由于之前在国家心肺血液研究所家庭心脏研究(NHLBI FHS)中发现了BMI的7q34和13q14的连锁证据，以及15q13的糖尿病连锁，我们调查了2号染色体和这些基因座之间的上位性。QTL 2p25与7q34、2q37与7q34、2q31与13q14、2q31-q36与15q13之间存在显著的上位性互作。这些结果表明，多个途径和因素涉及影响肥胖的遗传和环境效应。通过考虑其中一些已知因素，我们阐明了2p25上影响BMI和WC的QTL的连锁证据。2p25、2q24-q31和2q36-q37与7q34、13q14和15q13存在上位性互作。
We sought to identify quantitative trait loci (QTLs) by genome-wide linkage analysis for BMI and waist circumference (WC) exploring various strategies to address heterogeneity including covariate adjustments and complex models based on epistatic components of variance. Because cholesterol-lowering drugs and diabetes medications may affect adiposity and risk of coronary heart disease, we excluded subjects medicated for hypercholesterolemia and hyperglycemia. The evidence of linkage increased on 2p25 (BMI: lod = 1.59 vs. 2.43, WC: lod = 1.32 vs. 2.26). Because environmental and/or genetic components could mask the effect of a specific locus, we investigated further whether a QTL could influence adiposity independently of lipid pathway and dietary habits. Strong evidence of linkage on 2p25 (BMI: lod = 4.31; WC: lod = 4.23) was found using Willet’s dietary factors and lipid profile together with age and sex in adjustment. It suggests that lipid profile and dietary habits are confounding factors for detecting a 2p25 QTL for adiposity. Because evidence of linkage has been previously detected for BMI on 7q34 and 13q14 in National Heart, Lung, and Blood Institute Family Heart Study (NHLBI FHS), and for diabetes on 15q13, we investigated epistasis between chromosome 2 and these loci. Significant epistatic interactions were found between QTLs 2p25 and 7q34, 2q37 and 7q34, 2q31 and 13q14, and 2q31–q36 and 15q13. These results suggest multiple pathways and factors involving genetic and environmental effects influencing adiposity. By taking some of these known factors into account, we clarified our linkage evidence of a QTL on 2p25 influencing BMI and WC. The 2p25, 2q24–q31, and 2q36–q37 showed evidence of epistatic interaction with 7q34, 13q14, and 15q13.