Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts

By Yurii S. Aulchenko, Samuli Ripatti, I. Lindqvist, Dorret I. Boomsma, I. Heid, P. Pramstaller, Brenda W. J. H. Penninx, A. Janssens, James F. Wilson, Tim D. Spector and 47 more. Nature Genetics, 2008

934 citations recorded by the source corpus.

Recent genome-wide association (GWA) studies of lipids have been conducted in samples ascertained for other phenotypes, particularly diabetes. Here we report the first GWA analysis of loci affecting total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides sampled randomly from 16 population-based cohorts and genotyped using mainly the Illumina HumanHap300-Duo platform. Our study included a total of 17,797–22,562 persons, aged 18–104 years and from geographic regions spanning from the Nordic countries to Southern Europe. We established 22 loci associated with serum lipid levels at a genome-wide significance level (P < 5 × 10−8), including 16 loci that were identified by previous GWA studies. The six newly identified loci in our cohort samples are ABCG5 (TC, P = 1.5 × 10−11; LDL, P = 2.6 × 10−10), TMEM57 (TC, P = 5.4 × 10−10), CTCF-PRMT8 region (HDL, P = 8.3 × 10−16), DNAH11 (LDL, P = 6.1 × 10−9), FADS3-FADS2 (TC, P = 1.5 × 10−10; LDL, P = 4.4 × 10−13) and MADD-FOLH1 region (HDL, P = 6 × 10−11). For three loci, effect sizes differed significantly by sex. Genetic risk scores based on lipid loci explain up to 4.8% of variation in lipids and were also associated with increased intima media thickness (P = 0.001) and coronary heart disease incidence (P = 0.04). The genetic risk score improves the screening of high-risk groups of dyslipidemia over classical risk factors.

Subfields: Cancer Research, Genetics

View Paper: https://www.semanticscholar.org/paper/2880c6e404d399865a1a0ecadd5cc4d5cde3cd68

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

In Genetics

Citations in the corpus

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk (2010, neutral): “…FG-associated variant in MADD was not associated with lipid levels and is not in LD (r 2 0.1) with a previously reported high-density lipoprotein cholesterol SNP (rs7395662)33, suggesting two independent signals within the same locus, one affecting lipid levels and the other FG levels (Table 3).”
A genomewide perspective of genetic variation in human metabolism (2009, background): “Three better-powered GWAS with lipid parameters have only recently confirmed this predictio”
Genetic diagnosis by whole exome capture and massively parallel DNA sequencing (2009, neutral): “9 cSNVs Synonymous (novel) 6,462 (253) 6,377 (212) 7,229 (284) 6,708 (235) 7,299 (365) 6,815 (240) Missense (novel) 5,091 (357) 4,986 (305) 5,731 (462) 5,226 (352) 5,672 (365) 5,341 (368) Premature termination (novel) 34 (6) 28 (7) 33 (10) 29 (8) 36 (5) 32 (7) Splice site (novel) 84 (10) 72 (8) 83 (”
Human genetic variation and its contribution to complex traits (2009, background): “It is important to note that GWA studies and meta-analyses of combined GWA studies have been conducted using 20,000 to 40,000 samples for lipid phenotypes (low- and high-density lipoprotein, total cholesterol and triglyceride levels”
Genome-wide association analysis of metabolic traits in a birth cohort from a founder population (2008, background): “In most cases the causal variant remains unidentified, and several of these SNPs are located in genes known to have substantial allelic heterogeneit”
Genetics and Beyond – The Transcriptome of Human Monocytes and Disease Susceptibility (2010, background): “For each locus identified in GWAS of lipid variables [21], blood pressure (BP) [22] and body mass index (BMI) [23], we selected the lead SNP or a tag SNP having an r(2)$0.”
The Rotterdam Study: 2010 objectives and design update (2007, background): “phenotypes and diseases from all major research lines in the Rotterdam Study [193–196].”
From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus (2010, positive): “The full Methods provides information about all experimental procedures: (1) description of association analyses in the population cohorts; (2) description of genotype-expression analyses in human liver, subcutaneous adipose, and omental adipose samples; (3) details for generation of luciferase expr”