Pleiotropy of cardiometabolic syndrome with obesity-related anthropometric traits determined using empirically derived kinships from the Busselton Health Study
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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.
The authors acknowledge the generous support for the 1994/1995 Busselton Health Study follow-up from Healthway, Western Australia, the numerous Busselton community volunteers who assisted with data collection and the study participants from the Shire of Busselton. The Busselton Health Study is supported by The Great Wine Estates of the Margaret River region of Western Australia. Support from the Royal Perth Hospital Medical Research Foundation is gratefully acknowledged.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
GC is supported by the National Health and Medical Research Council (APP1101320).
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