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

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 rela...

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Main Authors: Cadby, G., Melton, P., McCarthy, N., Almeida, M., Williams-Blangero, S., Curran, J., VandeBerg, J., Hui, J., Beilby, J., Musk, A., James, A., Hung, J., Blangero, J., Moses, Eric
Format: Journal Article
Published: 2017
Online Access:http://hdl.handle.net/20.500.11937/59507
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author Cadby, G.
Melton, P.
McCarthy, N.
Almeida, M.
Williams-Blangero, S.
Curran, J.
VandeBerg, J.
Hui, J.
Beilby, J.
Musk, A.
James, A.
Hung, J.
Blangero, J.
Moses, Eric
author_facet Cadby, G.
Melton, P.
McCarthy, N.
Almeida, M.
Williams-Blangero, S.
Curran, J.
VandeBerg, J.
Hui, J.
Beilby, J.
Musk, A.
James, A.
Hung, J.
Blangero, J.
Moses, Eric
author_sort Cadby, G.
building Curtin Institutional Repository
collection Online Access
description 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.
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spelling curtin-20.500.11937-595072018-02-16T03:16:06Z Pleiotropy of cardiometabolic syndrome with obesity-related anthropometric traits determined using empirically derived kinships from the Busselton Health Study Cadby, G. Melton, P. McCarthy, N. Almeida, M. Williams-Blangero, S. Curran, J. VandeBerg, J. Hui, J. Beilby, J. Musk, A. James, A. Hung, J. Blangero, J. Moses, Eric 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. 2017 Journal Article http://hdl.handle.net/20.500.11937/59507 10.1007/s00439-017-1856-x restricted
spellingShingle Cadby, G.
Melton, P.
McCarthy, N.
Almeida, M.
Williams-Blangero, S.
Curran, J.
VandeBerg, J.
Hui, J.
Beilby, J.
Musk, A.
James, A.
Hung, J.
Blangero, J.
Moses, Eric
Pleiotropy of cardiometabolic syndrome with obesity-related anthropometric traits determined using empirically derived kinships from the Busselton Health Study
title Pleiotropy of cardiometabolic syndrome with obesity-related anthropometric traits determined using empirically derived kinships from the Busselton Health Study
title_full Pleiotropy of cardiometabolic syndrome with obesity-related anthropometric traits determined using empirically derived kinships from the Busselton Health Study
title_fullStr Pleiotropy of cardiometabolic syndrome with obesity-related anthropometric traits determined using empirically derived kinships from the Busselton Health Study
title_full_unstemmed Pleiotropy of cardiometabolic syndrome with obesity-related anthropometric traits determined using empirically derived kinships from the Busselton Health Study
title_short Pleiotropy of cardiometabolic syndrome with obesity-related anthropometric traits determined using empirically derived kinships from the Busselton Health Study
title_sort pleiotropy of cardiometabolic syndrome with obesity-related anthropometric traits determined using empirically derived kinships from the busselton health study
url http://hdl.handle.net/20.500.11937/59507