Year-end Sale % OFF 
Abstract
To demonstrate the loci that relate to high-density lipoprotein cholesterol (HDL-C) levels and genetic sex heterogeneity, we enrolled 41,526 participants aged between 30 and 70 years old from the Taiwan Biobank in a genome-wide association study. We applied the Manhattan plot to display the p-values estimated for the relationships between loci and low HDL-C. A total of 160 variants were significantly associated with low HDL-C. The genotype TT of rs1364422 located in the KLF14 gene has 1.30 (95% CI=1.20 - 1.42) times the risk for low-HDL compared to genotype CC in females (log(-p) =8.98). Moreover, the genes APOC1, APOE, PVRL2, and TOMM40 were associated significantly with low-HDL-C in males only. Excluding the variants with high linkage disequilibrium, we revealed the rs429358 located in APOE as the major genetic variant for lowering HDL-C, in which genotype CT has 1.24 (95% CI= 1.16 - 1.32) times the risk. In addition, we also examine 12 genes related to HDL-C in both sexes, including LPL, ABCA1, APOA5, BUD13, ZPR1, ALDH1A2, LIPC, CETP, HERPUD1, LIPG, ANGPTL8, and DOCK6. In conclusion, low-HDL-C is a genetic and sex-specific phenotype, and we discovered that the APOE and KLF14 are specific to low-HDL-C for men and women, respectively.
Highlights
The level of low high-density lipoproteins cholesterol (HDL-C) is a common indicator of metabolic syndrome and dyslipidemia (Lazo-Porras et al, 2016)
Considering the associations between demographic characteristics and low-HDL-C, the results showed that diastolic blood pressure, triglycerides, systolic blood pressure, waist circumference, body mass index (BMI), and fasting glucose were significantly associated with low HDL-C in both males and females
We performed a genome-wide association studies (GWAS) study to reveal the genetic variants associated with low-HDL-C and found twelve genes related to HDL-C in both genders
Summary
The level of low high-density lipoproteins cholesterol (HDL-C) is a common indicator of metabolic syndrome and dyslipidemia (Lazo-Porras et al, 2016). HDL-C showed a strong inherited basis with heritability estimates of 40-60% (Weissglas-Volkov and Pajukanta, 2010). The higher HDL-C levels showed a protective effect from CAD even after adjustment of non–HDL-C and triglycerides (Emerging Risk Factors Collaboration et al, 2009). Given the public health relevance and the strong genetic component (von Eckardstein et al, 2000; Weiss et al, 2006; Emerging Risk Factors Collaboration et al, 2009; Laks et al, 2011), considerable efforts have been made to elucidate the genetic architecture for lower HDL-C levels. Several largescale studies, culminating in the 2013 Global Lipids Genetics Consortium, have contributed to the discovery and validation of genetic loci associated with HDL-C levels (Teslovich et al, 2010; Willer et al, 2013). The disconcordant heritability obtained from different populations and distinct sexes from previous HDL studies (Weiss et al, 2006; Souren et al, 2007) indicated that genetic factors of HDL-C may act in a population- and/or sex-specific manner
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
