Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA.
Obesity (Silver Spring). 2009 Dec;17(12):2182-9. doi: 10.1038/oby.2009.141. Epub 2009 May 21.
The National Heart, Lung, and Blood Institute Family Heart Study (FHS) genome-wide linkage scan identified a region of chromosome 7q31-34 with a lod score of 4.9 for BMI at D7S1804 (131.9 Mb). We report the results of linkage and association to BMI in this region for two independent FHS samples. The first sample includes 225 FHS pedigrees with evidence of linkage to 7q31-34, using 1,132 single-nucleotide polymorphisms (SNPs) and 7 microsatellites. The second represents a case-control sample (318 cases; BMI >25 and 325 controls; BMI <25) derived from unrelated FHS participants who were not part of the genome scan. The latter set was genotyped for 606 SNPs, including 37 SNPs with prior evidence for association in the linked families. Although variance components linkage analysis using only SNPs generated a peak lod score that coincided with the original linkage scan at 131.9 Mb, a conditional linkage analysis showed evidence of a second quantitative trait locus (QTL) near 143 cM influencing BMI. Three SNPs (rs161339, rs12673281, and rs1993068) located near the three genes pleiotrophin (PTN), diacylglycerol (DAG) kinase iota (DGK iota), and cholinergic receptor, muscarinic 2 (CHRM2) demonstrated significant association in both linked families (P = 0.0005, 0.002, and 0.03, respectively) and the case-control sample (P = 0.01, 0.0003, and 0.03, respectively), regardless of the genetic model tested. These findings suggest that several genes may be associated with BMI in the 7q31-34 region.
国家心肺血液研究所家族心脏研究（FHS）全基因组连锁扫描在 D7S1804（131.9Mb）处发现了一个染色体 7q31-34 区域，其 BMI 的 lod 得分为 4.9。我们报告了两个独立的 FHS 样本中该区域与 BMI 的连锁和关联结果。第一个样本包括 225 个具有 7q31-34 连锁证据的 FHS 家系，使用了 1132 个单核苷酸多态性（SNP）和 7 个微卫星。第二个是来自无关 FHS 参与者的病例对照样本（318 例；BMI>25 和 325 例；BMI<25），他们不是基因组扫描的一部分。后者为 606 个 SNP 进行了基因分型，包括 37 个在连锁家系中有先前关联证据的 SNP。虽然仅使用 SNP 的方差成分连锁分析产生了一个与原始连锁扫描在 131.9Mb 处一致的峰值 lod 得分，但条件连锁分析显示，在影响 BMI 的 143cM 附近存在第二个数量性状基因座（QTL）的证据。三个 SNP（rs161339、rs12673281 和 rs1993068）位于多效蛋白（PTN）、二酰基甘油（DAG）激酶iota（DGK iota）和胆碱能受体，毒蕈碱 2（CHRM2）三个基因附近，在连锁家系（P=0.0005、0.002 和 0.03）和病例对照样本（P=0.01、0.0003 和 0.03）中均表现出显著关联，无论测试的遗传模型如何。这些发现表明，7q31-34 区域的几个基因可能与 BMI 相关。
