Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Int J Obes (Lond). 2021 Jul;45(7):1532-1541. doi: 10.1038/s41366-021-00817-2. Epub 2021 Apr 27.
BACKGROUND/OBJECTIVES: Neck circumference, an index of upper airway fat, has been suggested to be an important measure of body-fat distribution with unique associations with health outcomes such as obstructive sleep apnea and metabolic disease. This study aims to study the genetic bases of neck circumference.
We conducted a multi-ethnic genome-wide association study of neck circumference, adjusted and unadjusted for BMI, in up to 15,090 European Ancestry (EA) and African American (AA) individuals. Because sexually dimorphic associations have been observed for anthropometric traits, we conducted both sex-combined and sex-specific analysis.
We identified rs227724 near the Noggin (NOG) gene as a possible quantitative locus for neck circumference in men (N = 8831, P = 1.74 × 10) but not in women (P = 0.08). The association was replicated in men (N = 1554, P = 0.045) in an independent dataset. This locus was previously reported to be associated with human height and with self-reported snoring. We also identified rs13087058 on chromosome 3 as a suggestive locus in sex-combined analysis (N = 15090, P = 2.94 × 10; replication P =0.049). This locus was also associated with electrocardiogram-assessed PR interval and is a cis-expression quantitative locus for the PDZ Domain-containing ring finger 2 (PDZRN3) gene. Both NOG and PDZRN3 interact with members of transforming growth factor-beta superfamily signaling proteins.
Our study suggests that neck circumference may have unique genetic basis independent of BMI.
背景/目的：颈围是上呼吸道脂肪的指标，它被认为是身体脂肪分布的重要衡量标准，与阻塞性睡眠呼吸暂停和代谢性疾病等健康结果有独特的关联。本研究旨在研究颈围的遗传基础。
我们对颈围进行了一项多民族全基因组关联研究，对多达 15090 名欧洲血统（EA）和非裔美国人（AA）个体进行了调整和未调整体重指数（BMI）的调整。由于已经观察到了与人体测量特征有关的性别二态性关联，我们进行了男女混合和性别特异性分析。
我们在男性（N=8831，P=1.74×10-7）中发现了位于 Noggin（NOG）基因附近的 rs227724 是颈围的一个可能的数量基因座，但在女性中则不然（P=0.08）。该关联在独立数据集的男性中得到了复制（N=1554，P=0.045）。该基因座以前曾被报道与人类身高和自我报告的打鼾有关。我们还在男女混合分析中确定了染色体 3 上的 rs13087058 为提示性基因座（N=15090，P=2.94×10-7；复制 P=0.049）。该基因座也与心电图评估的 PR 间隔有关，是 PDZ 结构域包含的指环指蛋白 2（PDZRN3）基因的顺式表达数量基因座。NOG 和 PDZRN3 都与转化生长因子-β超家族信号蛋白的成员相互作用。
我们的研究表明，颈围可能具有与 BMI 无关的独特遗传基础。
