Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies : The CHARGE Consortium
Dehghan, A., Bis, J. C., White, C. C., Smith, A. V., Morrison, A. C., Cupples, L. A., Trompet, S., Chasman, D. I., Lumley, T., Völker, U., Buckley, B. M., Ding, J., Jensen, M. K., Folsom, A. R., Kritchevsky, S. B., Girman, C. J., Ford, I., Dörr, M., Salomaa, V., . . . O'Donnell, C. J. (2016). Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies : The CHARGE Consortium. PLoS ONE, 11(3), Article e0144997. https://doi.org/10.1371/journal.pone.0144997
Published inPLoS ONE
Background Data are limited on genome-wide association studies (GWAS) for incident coronary heart disease (CHD). Moreover, it is not known whether genetic variants identified to date also associate with risk of CHD in a prospective setting. Methods We performed a two-stage GWAS analysis of incident myocardial infarction (MI) and CHD in a total of 64,297 individuals (including 3898 MI cases, 5465 CHD cases). SNPs that passed an arbitrary threshold of 5×10−6 in Stage I were taken to Stage II for further discovery. Furthermore, in an analysis of prognosis, we studied whether known SNPs from former GWAS were associated with total mortality in individuals who experienced MI during follow-up. Results In Stage I 15 loci passed the threshold of 5×10−6; 8 loci for MI and 8 loci for CHD, for which one locus overlapped and none were reported in previous GWAS meta-analyses. We took 60 SNPs representing these 15 loci to Stage II of discovery. Four SNPs near QKI showed nominally significant association with MI (p-value<8.8×10−3) and three exceeded the genome-wide significance threshold when Stage I and Stage II results were combined (top SNP rs6941513: p = 6.2×10−9). Despite excellent power, the 9p21 locus SNP (rs1333049) was only modestly associated with MI (HR = 1.09, p-value = 0.02) and marginally with CHD (HR = 1.06, p-value = 0.08). Among an inception cohort of those who experienced MI during follow-up, the risk allele of rs1333049 was associated with a decreased risk of subsequent mortality (HR = 0.90, p-value = 3.2×10−3). Conclusions QKI represents a novel locus that may serve as a predictor of incident CHD in prospective studies. The association of the 9p21 locus both with increased risk of first myocardial infarction and longer survival after MI highlights the importance of study design in investigating genetic determinants of complex disorders. ...
PublisherPublic Library of Science
Publication in research information system
MetadataShow full item record
Except where otherwise noted, this item's license is described as This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Showing items with similar title or keywords.
Sauna bathing is associated with reduced cardiovascular mortality and improves risk prediction in men and women: a prospective cohort study Laukkanen, Tanjaniina; Kunutsor, Setor K.; Khan, Hassan; Willeit, Peter; Zaccardi, Francesco; Laukkanen, Jari (BioMed Central, 2018)Background: Previous evidence indicates that sauna bathing is related to a reduced risk of fatal cardiovascular disease (CVD) events in men. The aim of this study was to investigate the relationship between sauna habits ...
Machine learning models in predicting health care costs in patients with a recent acute coronary syndrome : A prospective pilot study Hautala, Arto J.; Shavazipour, Babooshka; Afsar, Bekir; Tulppo, Mikko P.; Miettinen, Kaisa (Elsevier, 2023)Background Health care budgets are limited requiring the optimal use of resources. Machine learning (ML) methods may have an enormous potential for effective use of health care resources. Objective We assessed the ...
Body size at birth and coronary heart disease-related hospital care in adult men : Findings from the Helsinki Birth Cohort Study von Bonsdorff, Monika; von Bonsdorff, Mikaela; Martikainen, Janne; Salonen, Minna; Kajantie, Eero; Kautiainen, Hannu; Eriksson, Johan G. (Informa Healthcare ; Taylor & Francis Group; Finnish Medical Society Duodecim, 2017)Aim: We investigated, among those who had been hospitalized at least once due to coronary heart disease (CHD), the relationship between ponderal index (PI, birthweight/length3) at birth, a measure of thinness, and the age ...
Kunutsor, Setor K.; Khan, Hassan; Zaccardi, Francesco; Laukkanen, Tanjaniina; Willeit, Peter; Laukkanen, Jari (American Academy of Neurology, 2018)Objective To assess the association between frequency of sauna bathing and risk of future stroke. Methods Baseline habits of sauna bathing were assessed in 1,628 adult men and women aged 53–74 years (mean age, 62.7 ...
Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium CREAM consortium (Springer, 2015)To identify genetic variants associated with refractive astigmatism in the general population, metaanalyses of genome-wide association studies were performed for: White Europeans aged at least 25 years (20 cohorts, N ...