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Hum Genet. 2018 Jan;137(1):45-53. doi: 10.1007/s00439-017-1856-x. Epub 2017 Nov 27.

Pleiotropy of cardiometabolic syndrome with obesity-related anthropometric traits determined using empirically derived kinships from the Busselton Health Study.

Author information

1
Centre for Genetic Origins of Health and Disease, Faculty of Health and Medical Sciences, The University of Western Australia, Perth, Australia. gemma.cadby@uwa.edu.au.
2
Centre for Genetic Origins of Health and Disease, Faculty of Health and Medical Sciences, The University of Western Australia, Perth, Australia.
3
Faculty of Health Sciences, Curtin University, Perth, Australia.
4
South Texas Diabetes and Obesity Institute, The University of Texas Rio Grande Valley School of Medicine, Brownsville, USA.
5
Busselton Population Medical Research Institute Inc., Perth, Australia.
6
PathWest Laboratory Medicine, Perth, WA, Australia.
7
School of Population and Global Health, The University of Western Australia, Perth, Australia.
8
Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Perth, Australia.
9
School of Medicine, The University of Western Australia, Perth, Australia.
10
Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, Perth, Australia.
11
Department of Cardiovascular Medicine, Sir Charles Gairdner Hospital, Perth, Australia.

Abstract

Over two billion adults are overweight or obese and therefore at an increased risk of cardiometabolic syndrome (CMS). Obesity-related anthropometric traits genetically correlated with CMS may provide insight into CMS aetiology. The aim of this study was to utilise an empirically derived genetic relatedness matrix to calculate heritabilities and genetic correlations between CMS and anthropometric traits to determine whether they share genetic risk factors (pleiotropy). We used genome-wide single nucleotide polymorphism (SNP) data on 4671 Busselton Health Study participants. Exploiting both known and unknown relatedness, empirical kinship probabilities were estimated using these SNP data. General linear mixed models implemented in SOLAR were used to estimate narrow-sense heritabilities (h 2) and genetic correlations (r g) between 15 anthropometric and 9 CMS traits. Anthropometric traits were adjusted by body mass index (BMI) to determine whether the observed genetic correlation was independent of obesity. After adjustment for multiple testing, all CMS and anthropometric traits were significantly heritable (h 2 range 0.18-0.57). We identified 50 significant genetic correlations (r g range: - 0.37 to 0.75) between CMS and anthropometric traits. Five genetic correlations remained significant after adjustment for BMI [high density lipoprotein cholesterol (HDL-C) and waist-hip ratio; triglycerides and waist-hip ratio; triglycerides and waist-height ratio; non-HDL-C and waist-height ratio; insulin and iliac skinfold thickness]. This study provides evidence for the presence of potentially pleiotropic genes that affect both anthropometric and CMS traits, independently of obesity.

PMID:
29181734
DOI:
10.1007/s00439-017-1856-x

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