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Author (up) Holmen, O.L.; Zhang, H.; Zhou, W.; Schmidt, E.; Hovelson, D.H.; Langhammer, A.; Lochen, M.-L.; Ganesh, S.K.; Mathiesen, E.B.; Vatten, L.; Platou, C.; Wilsgaard, T.; Chen, J.; Skorpen, F.; Dalen, H.; Boehnke, M.; Abecasis, G.R.; Njolstad, I.; Hveem, K.; Willer, C.J. url  doi
  Title No large-effect low-frequency coding variation found for myocardial infarction Type Journal Article
  Year 2014 Publication Human Molecular Genetics Abbreviated Journal Hum Mol Genet  
  Volume Issue Pages  
  Keywords HUNT3  
  Abstract Genome-wide association studies have identified variants, primarily common, that are associated with coronary artery disease or myocardial infarction (MI), but have not tested the majority of the low frequency and rare variation in the genome. We explored the hypothesis that previously untested low frequency (1-5% minor allele frequency) and rare (<1% minor allele frequency) coding variants are associated with MI. We genotyped 2906 MI cases and 6738 non-MI controls from Norway using the Illumina HumanExome Beadchip, allowing for direct genotyping of 85 972 polymorphic coding variants as well as 48 known GWAS SNPs. We followed-up 34 coding variants in an additional 2350 MI cases and 2318 controls from Norway. We evaluated exome array coverage in a subset of these samples using whole exome sequencing (N = 151). The exome array provided successful genotyping for an estimated 72.5% of Norwegian loss-of-function or missense variants with frequency >1% and 66.2% of variants <1% frequency observed more than once. Despite 80% power in the two-stage study (N = 14 312) to detect association with low-frequency variants with high effect sizes [odds ratio (OR) >1.86 and >1.36 for 1 and 5% frequency, respectively], we did not identify any novel genes or single variants that reached significance. This suggests that low-frequency coding variants with large effect sizes (OR >2) may not exist for MI. Larger sample sizes may identify coding variants with more moderate effects.  
  Address HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, 7600 Levanger, Norway  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0964-6906 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:24728188 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1626  
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