| 1. |
- de Vries, Paul S., et al.
(author)
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Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
- 2019
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In: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
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Journal article (peer-reviewed)abstract
- A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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| 2. |
- Li, Xiaonan, et al.
(author)
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Feeding Infants Formula With Probiotics or Milk Fat Globule Membrane : A Double-Blind, Randomized Controlled Trial
- 2019
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In: Frontiers in Pediatrics. - : Frontiers Media SA. - 2296-2360. ; 7
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Journal article (peer-reviewed)abstract
- Purpose: To evaluate effects on growth and infection rates of supplementing infant formula with the probiotic Lactobacillus paracasei ssp. paracasei strain F19 (F19) or bovine milk fat globule membrane (MFGM).Methods: In a double-blind, randomized controlled trial, 600 infants were randomized to a formula supplemented with F19 or MFGM, or to standard formula (SF). A breastfed group was recruited as reference (n = 200).The intervention lasted from age 21 ± 7 days until 4 months, and infants were followed until age one year.Results: Both experimental formulas were well tolerated and resulted in high compliance. The few reported adverse events were not likely related to formula, with the highest rates in the SF group, significantly higher than for the F19-supplemented infants (p = 0.046). Weight or length gain did not differ during or after the intervention among the formula-fed groups, with satisfactory growth. During the intervention, overall, the experimental formula groups did not have more episodes of diarrhea, fever, or days with fever than the breastfed infants. However, compared to the breastfed infants, the SF group had more fever episodes (p = 0.021) and days with fever (p = 0.036), but not diarrhea. Compared with the breastfed group, the F19-supplemented infants but not the other two formula groups had more visits/unscheduled hospitalizations (p = 0.015) and borderline more episodes of upper respiratory tract infections (p = 0.048).Conclusions: Both the MFGM- and F19-supplemented formulas were safe and well-tolerated, leading to few adverse effects, similar to the breastfed group and unlike the SF group. During the intervention, the MFGM-supplemented infants did not differ from the breastfed infants in any primary outcome.
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| 3. |
- Sung, Yun Ju, et al.
(author)
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A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
- 2019
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In: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 28:15, s. 2615-2633
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Journal article (peer-reviewed)abstract
- Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
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