Susceptibility loci for metabolic syndrome and metabolic components identified in Han Chinese: a multi‐stage genome‐wide association study

Abstract

Metabolic syndrome (MetS), a cluster of metabolic disturbances that increase the risk for cardiovascular disease and diabetes, was because of genetic susceptibility and environmental risk factors. To identify the genetic variants associated with MetS and metabolic components, we conducted a genome‐wide association study followed by replications in totally 12,720 participants from the north, north‐eastern and eastern China. In combined analyses, independent of the top known signal at rs651821 on APOA5, we newly identified a secondary triglyceride‐associated signal at rs180326 on BUD13 (P combined = 2.4 × 10−8). Notably, by an integrated analysis of the genotypes and the serum levels of APOA5, BUD13 and triglyceride, we observed that BUD13 was another potential mediator, besides APOA5, of the association between rs651821 and serum triglyceride. rs671 (ALDH2), an east Asian‐specific common variant, was found to be associated with MetS (P combined = 9.7 × 10−22) in Han Chinese. The effects of rs671 on metabolic components were more prominent in drinkers than in non‐drinkers. The replicated loci provided information on the genetic basis and mechanisms of MetS and metabolic components in Han Chinese.

Common genetic variation in obesity, lipid transfer genes and risk of Metabolic Syndrome: Results from IDEFICS/I.Family study and meta-analysis

“…Over the past decade, common genetic loci have been reported to be associated with MetS in different studies, mostly at a single time-point using a cross-sectional or a case-control approach 7,76,78 . Our study took a step ahead in investigating 350 pre-selected loci for their longitudinal association with a continuous MetS score during the transition from childhood to adolescence in a pan-European cohort of children with a follow-up period of up to seven years.…”

“…This has also been observed in the genetic association studies suggesting that genetic effects on lipid levels are more pronounced than for other traits 10 . Most of the genetic association studies for MetS have been conducted in adult population 5,10,11 and are limited by the usage of one-point measurements 7,[12][13][14] . As the prevalence of MetS in children and young adults is increasing 15 , a better understanding of the genetics that underlies MetS throughout childhood and adolescence will provide critical insights into the origin of the disease.…”

Influence of multiple apolipoprotein A-I and B genetic variations on insulin resistance and metabolic syndrome in obstructive sleep apnea

“…Both genetic and environmental factors play an important role in insulin resistance and MetS [12][13][14][15]. Although signi cant evidence links OSA to insulin resistance and MetS [3,16], little is known about the roles of the genetic factors of lipoproteins involved in insulin resistance and MetS in OSA.…”

The more the merrier? Multivariate approaches to genome-wide association analysis

“…However, often data on multiple correlated traits are available and sometimes traits treated as univariate are actually multivariate in nature. For instance, GWA studies on metabolic syndrome (e.g., Zhu et al, 2017, Kristiansson et al, 2012) base the case-control status on the joint evaluation of multiple measures (e.g., waist circumference, body mass index, blood pressure, and various blood measures). Similarly, GWA studies on psychiatric disorders like major depressive disorder (e.g., Howard et al, 2018, Wray et al, 2018) generally use case-control status variables that originate in the joint evaluation of multiple clinical criteria, and GWA studies on cognitive ability use cognitive scores that summarize the performance on batteries of cognitive tests covering e.g., vocabulary, general knowledge, and memory (e.g., Savage et al, 2018, Benyamin et al, 2014; Davis et al, 2010).…”