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- Feitosa, Mary F., et al.
(författare)
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Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
- 2018
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Ingår i: PLOS ONE. - : Public library science. - 1932-6203. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
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| 2. |
- Quintana, Hedley Knewjen, et al.
(författare)
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Comorbidities in relation to fatali of first myocardial infarction
- 2018
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Ingår i: Cardiovascular pathology. - : ELSEVIER SCIENCE INC. - 1054-8807 .- 1879-1336. ; 32, s. 32-37
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Present knowledge concerning potential associations between comorbidities and the fatality of a first myocardial infarction (MI) is limited.Aim: To identify comorbidities in 45-70-year-old individuals who suffered a first MI and died within 7 days in Stockholm County from 1992-1994. In addition, to assess how each of the comorbidities identified, as well as the number of hospitalizations during the 10-year period prior to the MI, was associated with MI fatality.Methods: The data collected on our inception cohort of 1984 first Ml, of which 524 were fatal within 7 days, were primarily self-reported, proxy-reported by questionnaire and/or extracted from comprehensive national registers. Comorbidilies among fatal cases with a prevalence >2% were identified. Risk ratios (with 95% confidence intervals) for the association of Ml fatality with number of prior hospitalizations and specific comorbidities were calculated using binomial regression with log link. A structured review of autopsy reports on fatal cases was performed in order to identify additional indicators of comorbidities.Results: After adjusting for sex, age and disposable income, the number of previous hospitalizations was associated with 7-day Ml fatality. Of the comorbidities identified as prevalent in fatal cases, the following were associated with 7-day fatality in crude analysis: epilepsy, heart failure, stroke, alcoholism, cancer, renal diseases, asthma, psychiatric diseases, diabetes, and rheumatoid arthritis. Indicators of comorbidities identified from autopsy data included a silent MI, severe atherosclerosis of the abdominal aorta, and hepatic steatosis. Adjustments for sex and age (although not possible for epilepsy and alcoholism), did not substantially alter results.Conclusions: Our current findings indicate that in connection with a first MI, particular attention should be paid to those with repeated prior hospitalizations and/or epilepsy, heart failure, stroke, alcoholism, cancer, renal diseases, asthma, psychiatric diseases, diabetes and rheumatoid arthritis.
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