Abstract
Background/objectivesNeck 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.MethodsWe 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.ResultsWe identified rs227724 near the Noggin (NOG) gene as a possible quantitative locus for neck circumference in men (N = 8831, P = 1.74 × 10−9) 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 × 10−7; 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.ConclusionsOur study suggests that neck circumference may have unique genetic basis independent of BMI.
Highlights
Our study suggests that neck circumference may have unique genetic basis independent of body mass index (BMI)
Increased body fat is associated with a range of adverse health conditions, such as metabolic syndrome [1, 2], insulin resistance [3], type 2 diabetes (T2D) [4], cardiovascular diseases [5], and obstructive sleep apnea (OSA) [6]
9.7% of the individuals were of African ancestry and were 90.3% of European ancestry
Summary
Increased body fat is associated with a range of adverse health conditions, such as metabolic syndrome [1, 2], insulin resistance [3], type 2 diabetes (T2D) [4], cardiovascular diseases [5], and obstructive sleep apnea (OSA) [6]. Body weight is most commonly estimated by calculating the body mass index (BMI). Genome-wide association studies (GWAS) in large cohorts have identified hundreds of BMIassociated loci and improved our understanding of the genetic basis of BMI [7, 8]. BMI does not differentiate between fat and lean body mass nor characterize differences in body-fat depots, limiting its ability to characterize body composition or identify individuals with differences in body-fat distribution. BMI was developed to characterize weight rather than fat [9]. More direct measures of body-fat distribution obtained through anthropometric measurements include waist circumference, hip circumference, and waist-to-hip ratio. Independent of BMI, large GWAS identified many unique loci for these traits [10], suggesting that there are specific genetic determinants of different body-fat depots
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