Genome-wide association of early-onset myocardial infarction with common single nucleotide polymorphisms, common copy number variants, and rare copy number variants

By Sekar Kathiresan, Benjamin F. Voight, Shaun Purcell, K. Musunuru, D. Ardissino, P. Mannucci, Sonia S Anand, J. Engert, N. Samani, H. Schunkert and 113 more. Nature Genetics, 2009

1,094 citations recorded by the source corpus.

We conducted a genome-wide association study testing single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for association with early-onset myocardial infarction in 2,967 cases and 3,075 controls. We carried out replication in an independent sample with an effective sample size of up to 19,492. SNPs at nine loci reached genome-wide significance: three are newly identified (21q22 near MRPS6-SLC5A3-KCNE2, 6p24 in PHACTR1 and 2q33 in WDR12) and six replicated prior observations (9p21, 1p13 near CELSR2-PSRC1-SORT1, 10q11 near CXCL12, 1q41 in MIA3, 19p13 near LDLR and 1p32 near PCSK9). We tested 554 common copy number polymorphisms (>1% allele frequency) and none met the pre-specified threshold for replication (P < 10−3). We identified 8,065 rare CNVs but did not detect a greater CNV burden in cases compared to controls, in genes compared to the genome as a whole, or at any individual locus. SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with myocardial infarction risk.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/de37b46392b8a12d2b95dafb83681275e59f177f

How researchers see this paper

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

In Genetics

In Molecular Biology

Citations in the corpus

Genome-Wide Association Analysis Identifies Variants Associated with Nonalcoholic Fatty Liver Disease That Have Distinct Effects on Metabolic Traits (2011, methodology): “The genetic ancestry the MIGen samples was explored by using the program Eigenstrat [46]; the first principal component was the most significant and correlated with the commonly observed Northwest- Southeast axis within Europe [20] and genetic ancestry along this principal component is correlated wi”
Genetics and Beyond – The Transcriptome of Human Monocytes and Disease Susceptibility (2010, background): “Several loci associated with coronary artery disease (CAD) have been identified by GWAS [26–29].”
Enhancing the Prioritization of Disease-Causing Genes through Tissue Specific Protein Interaction Networks (2012, background): “Second, the genes within these intervals are examined for their causal relation to the disease [1– 3].”