Linkage and potential association of obesity-related phenotypes with two genes on chromosome 12q24 in a female dizygous twin cohort
Linkage and potential association of obesity-related phenotypes with two genes on chromosome 12q24 in a female dizygous twin cohort
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DOI：
10.1038/sj.ejhg.5201551
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发表时间：
2006-03-01
影响因子：
5.2
通讯作者：
Spector, TD
中科院分区：
文献类型：
--
作者：
Wilson, SG;Adam, G;Spector, TD
肥胖是一种具有复杂表型的多因素疾病。它是糖尿病和高血压的重要危险因素。我们评估了一大群双胞胎中与肥胖相关的特征，并进行了全基因组连锁扫描和位置候选分析，以确定在调节女性脂肪量和分布中发挥作用的基因。研究人员对来自 1094 个家系的异卵女性双胞胎进行了研究（平均年龄 47.07 +/- 11.5 岁（范围 18-79 岁））。非参数多点连锁分析显示，中央脂肪量与 LOD 2.2 的 12q24 (141 cM) 存在关联，体重指数与 LOD 1.3 的 8q11 (67 cM) 存在关联，支持了之前建立的关联数据。提示关联的新区域是 6q12 的总脂肪百分比（LOD 2.4）和 2q37 的总瘦体重（LOD 2.4）。来自 1243 对双胞胎的扩展队列的后续精细绘图数据强化了中央脂肪量与 12q24 的联系（LOD 2.6；143 cM），并将 -1 LOD 支持区间缩小至 22 cM。总之，随后在 1102 名双胞胎队列中测试了 12q24 区间内 26 个位置候选基因的 45 个单核苷酸多态性 (SNP) 的关联性。单点 Monks-Kaplan 分析提供了中央脂肪量与两个基因 -PLA2G1B (P = 0.0067) 和 P2RX4 (P = 0.017) 中的 SNP 之间关联的证据。这些数据提供了 12q24 肥胖位点的复制和细化，并表明参与磷脂酶和嘌呤受体途径的基因可能调节脂肪积累和分布。
Obesity is a multifactorial disorder with a complex phenotype. It is a significant risk factor for diabetes and hypertension. We assessed obesity-related traits in a large cohort of twins and performed a genome-wide linkage scan and positional candidate analysis to identify genes that play a role in regulating fat mass and distribution in women. Dizygous female twin pairs from 1094 pedigrees were studied ( mean age 47.07 +/- 11.5 years ( range 18-79 years)). Nonparametric multipoint linkage analyses showed linkage for central fat mass to 12q24 (141 cM) with LOD 2.2 and body mass index to 8q11 (67 cM) with LOD 1.3, supporting previously established linkage data. Novel areas of suggestive linkage were for total fat percentage at 6q12 (LOD 2.4) and for total lean mass at 2q37 (LOD 2.4). Data from follow-up fine mapping in an expanded cohort of 1243 twin pairs reinforced the linkage for central fat mass to 12q24 (LOD 2.6; 143 cM) and narrowed the -1 LOD support interval to 22 cM. In all, 45 single-nucleotide polymorphisms ( SNPs) from 26 positional candidate genes within the 12q24 interval were then tested for association in a cohort of 1102 twins. Single-point Monks-Kaplan analysis provided evidence of association between central fat mass and SNPs in two genes -PLA2G1B (P = 0.0067) and P2RX4 (P = 0.017). These data provide replication and refinement of the 12q24 obesity locus and suggest that genes involved in phospholipase and purinoreceptor pathways may regulate fat accumulation and distribution.