de Toro-Martín J, Guénard F, Tchernof A, Deshaies Y, Pérusse L, Biron S, Lescelleur O, Biertho L, Marceau S, Vohl M-C
Institute of Nutrition and Functional Foods (INAF) Laval University Quebec Quebec Canada; School of Nutrition Laval University Quebec Quebec Canada.
School of Nutrition Laval University Quebec Quebec Canada; Quebec Heart and Lung Institute Research Center Quebec Quebec Canada.
Obes Sci Pract. 2016 Dec;2(4):407-414. doi: 10.1002/osp4.74. Epub 2016 Oct 21.
A novel single-nucleotide polymorphism (SNP) associated with morbid obesity was recently identified by exome sequencing. The purpose of this study was to follow up this low-frequency coding SNP located within the locus and associated with body mass index in order to reveal novel associations with obesity-related traits.
The body mass index-associated SNP (rs62623713 A>G [chr1:109476817/hg19]) and two tagging SNPs within the locus, rs9661614 T>C (chr1:109479215) and rs485660 G>A (chr1:109480810), were genotyped in the obesity ( = 3,017) and the infogene ( = 676) cohorts, which were further combined, leading to a larger cohort of 3,693 individuals. Association testing was performed by general linear models in the obesity cohort and validated by joint analysis in the combined cohort.
rs9661614 and rs485660 were significantly associated with hip circumference (HC) in the obesity cohort, with heterozygotes exhibiting a significantly lower HC. These results were validated by joint analysis for rs9661614 (false discovery rate [FDR]-corrected = 7.5 × 10) and, to a lesser extent, for rs485660 (FDR corrected = 3.9 × 10). The association with HC remained significant for rs9661614 when tested independently in women (FDR-corrected = 1.7 × 10), but not for rs485660 (FDR-corrected = 0.2). Both associations were absent in men.
This study reveals strong evidence for a novel association between rs9661614 (T>C) and HC in women, which likely reflects a preferential association of to a gynoid profile of fat distribution. The study findings support a clinical significance of worth considering when assessing risk factors associated with obesity.
最近通过外显子组测序鉴定出一种与病态肥胖相关的新型单核苷酸多态性（SNP）。本研究的目的是对位于该基因座内且与体重指数相关的这种低频编码SNP进行随访，以揭示与肥胖相关性状的新关联。
在肥胖队列（n = 3017）和信息基因队列（n = 676）中对与体重指数相关的SNP（rs62623713 A>G [chr1:109476817/hg19]）以及该基因座内的两个标签SNP，即rs9661614 T>C（chr1:109479215）和rs485660 G>A（chr1:109480810）进行基因分型，然后将这两个队列进一步合并，形成一个由3693名个体组成的更大队列。在肥胖队列中通过一般线性模型进行关联测试，并在合并队列中通过联合分析进行验证。
在肥胖队列中，rs9661614和rs485660与臀围（HC）显著相关，杂合子的臀围显著更低。rs9661614的这些结果通过联合分析得到验证（错误发现率[FDR]校正P = 7.5×10⁻⁵），rs485660的结果在较小程度上也得到验证（FDR校正P = 3.9×10⁻⁴）。当在女性中单独测试时，rs9661614与臀围的关联仍然显著（FDR校正P = 1.7×10⁻⁴），但rs485660与臀围的关联不显著（FDR校正P = 0.2）。在男性中这两种关联均不存在。
本研究揭示了rs9661614（T>C）与女性臀围之间新关联的有力证据，这可能反映了该基因与女性型脂肪分布的优先关联。研究结果支持在评估与肥胖相关的风险因素时，该基因具有值得考虑的临床意义。
