Discovery and refinement of loci associated with lipid levels

Abstract

Low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, and total cholesterol are heritable, modifiable, risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,578 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5×10−8, including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian, and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipids are often associated with cardiovascular and metabolic traits including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio, and body mass index. Our results illustrate the value of genetic data from individuals of diverse ancestries and provide insights into biological mechanisms regulating blood lipids to guide future genetic, biological, and therapeutic research.

Genetic studies of schizophrenia: an update

“…The same trend is observed in studies of other complex diseases and traits, such as obesity, height, and blood lipids [28][29][30] . This trend demands collaborative work from many investigators to ensure the successful discovery of risk genes for complex diseases.…”

Leveraging Multi-ethnic Evidence for Risk Assessment of Quantitative Traits in Minority Populations

“…1 At the same time, studies with expanding cohorts continue to uncover variants associated with a variety of traits and diseases, indicating moderate to high heritability. [2][3][4][5] Therefore, while genetic variation alone is insufficient for accurate disease or trait prediction, it is reasonable to expect that a summary score of all trait-relevant variants can meaningfully quantify the heritable component that underlies variation in complex traits or disease risks. Furthermore, this genetic score complements conventional non-genetic risk factors, and integration of genetic and non-genetic risk factors may lead to more accurate health assessment.…”

Variants at the APOE/C1/C2/C4 Locus Modulate Cholesterol Efflux Capacity Independently of High‐Density Lipoprotein Cholesterol

“…Because not all variants could be retrieved by LDlink, we selected α=1×10 −4 to declare significance in this secondary analysis (an effective Bonferroni correction for 500 tests). We also looked up CEC association results for variants associated with blood lipid levels (n=160 single‐nucleotide polymorphisms [SNPs]) or CAD risk (n=86 SNPs) by GWAS,22, 23, 24, 25, 26 using a statistical threshold of α=2.1×10 −4 (Bonferroni correction for 239 different variants). For these secondary analyses of candidate variants, we did not correct for the number of CEC phenotypes and statistical models to assess statistical significance.…”