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. 2021 Jul;45(7):1532-1541.
doi: 10.1038/s41366-021-00817-2. Epub 2021 Apr 27.

Genome-wide association study of neck circumference identifies sex-specific loci independent of generalized adiposity

Yaowu Liu  1 , Xiaoyu Zhang  2 , Jiwon Lee  3 , Diane Smelser  4 , Brian Cade  3   5 , Han Chen  6   7 , Hufeng Zhou  1 , H Lester Kirchner  8 , Xihong Lin  1   9 , Sutapa Mukherjee  10   11 , David Hillman  12 , Ching-Ti Liu  2 , Susan Redline  3   5 , Tamar Sofer  13   14   15
Affiliations

Genome-wide association study of neck circumference identifies sex-specific loci independent of generalized adiposity

Yaowu Liu et al. Int J Obes (Lond). 2021 Jul.

Abstract

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.

Methods: 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.

Results: We 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.

Conclusions: Our study suggests that neck circumference may have unique genetic basis independent of BMI.

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Conflict of interest statement

The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. HLK receives funding from Regeneron Pharmaceuticals as part of the DiscovEHR collaboration. Regeneron Pharmaceuticals had no involvement in the study design, execusion, nor interpretation of results for this study.

Figures

Fig. 1
Fig. 1. Manhattan plots of sex-combined analysis results for NCadjBMI.
The three panels from top to bottom correspond to the results from sex-combined analysis (a), males only (b), and females only (c).
See this image and copyright information in PMC

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