Gene-Targeted Analysis of Copy Number Variants Identifies 3 Novel Associations With Coronary Heart Disease Traits

Abstract

Background— Copy number variants (CNVs) are a major form of genomic variation, which may be implicated in complex disease phenotypes. However, investigation of the role of CNVs in coronary heart disease (CHD) traits has been limited. Methods and Results— We examined the use of the cnvHap algorithm for CNV detection, using data for 2500 men from the Second Northwick Park Heart Study (NPHS-II). An Illumina custom chip, including 722 single-nucleotide polymorphisms covering 76 coronary heart disease-trait genes, was used. Common CNVs were significantly associated (at P <0.05, after correction) with coronary heart disease phenotypes in 5 genes. Novel associations of CNVs in toll-like receptor-4 with apolipoprotein AI were replicated ( P <0.05) in the Whitehall II cohort (4887 subjects), whereas newly described associations of CNVs in sterol regulatory element-binding protein with apolipoprotein AI and associations of interleukin-6 signal transducer with apolipoprotein B were replicated in the data from 3546 subjects from the North Finnish Birth Cohort 1966 ( P <0.05). Conclusions— This study supports the use of CNV detection algorithms such as cnvHap as potential tools for the identification of novel CNVs, some of which show significant association and replication with coronary heart disease risk phenotypes. However, the functional basis for these associations requires further substantiation.

Mutation detection in Chinese patients with familial hypercholesterolemia

“…This might be caused by variations in other genes such as APOC3 and PNPLA5 (Jorgensen et al 2014, Lange et al 2014). Furthermore, CNVs also play a crucial role in FH for unique cases (Myocardial Infarction Genetics, Kathiresan, et al 2009, Costelloe et al 2012). Considering the serious phenotype of proband F11, we believe that genetic factors may have had a dominant effect.…”

“…For example, APOB mutations may cause the least severe phenotype of the three (Soutar and Naoumova 2007). Besides LDLR , APOB and PCSK9 mutations, some copy number variants (CNVs) (Myocardial Infarction Genetics, Kathiresan et al 2009; Costelloe et al 2012) and rare mutations in associated genes, such as LDLRAP1 (Maglio et al 2014), PNPLA5 (Lange et al 2014) and APOC3 (Jorgensen et al 2014) have also been reported in FH patients.…”

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“…However, the functional basis for these associations requires further substantiation. 23 Hospital Percutaneous Coronary Intervention Appropriateness and In-Hospital Procedural Outcomes: Insights From the NCDR Summary: Measuring PCI quality has traditionally focused on processes of care and postprocedural outcomes, such as in-hospital mortality, bleeding and vascular complication rates, and provision of guideline-recommended medications. PCI appropriateness is increasingly being incorporated into registries and quality improvement programs to measure the quality of patient selection for PCI, although the relationship to traditional PCI quality metrics is unknown.…”

Genomic structural variations for cardiovascular and metabolic comorbidity

“…The studies of CNVs in coronary artery disease have typically used DNA isolated from peripheral blood, and inconclusive results were obtained891011. The most pronounced genomic imbalance in patients with coronary artery disease and metabolic comorbidity are possibly detected in the target disease organs, such as coronary arteries.…”