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

Citation

Cadby, G and Melton, PE and McCarthy, NS and Almeida, M and Williams-Blangero, S and Curran, JE and VandeBerg, JL and Hui, J and Beilby, J and Musk, AW and James, AL and Hung, J and Blangero, J and Moses, EK, Pleiotropy of cardiometabolic syndrome with obesity-related anthropometric traits determined using empirically derived kinships from the Busselton Health Study, Human Genetics, 137, (1) pp. 45-53. ISSN 0340-6717 (2018) [Refereed Article]

Copyright Statement

Springer-Verlag GmbH Germany, part of Springer Nature 2017

DOI: doi:10.1007/s00439-017-1856-x

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 (h2) 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 (h2 range 0.18-0.57). We identified 50 significant genetic correlations (rg 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.

Item Details

Item Type:Refereed Article
Keywords:pleiotropy, genetic correlations, emprical kinship, family studies, risk factors
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Gene mapping
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Melton, PE (Dr Phillip Melton)
ID Code:141399
Year Published:2018
Web of Science® Times Cited:4
Deposited By:Menzies Institute for Medical Research
Deposited On:2020-10-19
Last Modified:2021-06-03
Downloads:0

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