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Sökning: WFRF:(McKenzie CA)
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Ridker, PM, et al. (författare)
Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients
Ingår i: The New England journal of medicine. - : Massachusetts Medical Society. - 1533-4406 .- 0028-4793. ; 376:16, s. 1527-1539
Wood, Andrew R, et al. (författare)
Defining the role of common variation in the genomic and biological architecture of adult human height.
Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.
Bentley, Amy R., et al. (författare)
Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:4, s. 636-
The concentrations of high- and low-density-lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene-smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. Combined meta-analyses identified 13 new loci associated with lipids, some of which were detected only because association differed by smoking status. Additionally, we demonstrate the importance of including diverse populations, particularly in studies of interactions with lifestyle factors, where genomic and lifestyle differences by ancestry may contribute to novel findings.
Do, Ron, et al. (författare)
Common variants associated with plasma triglycerides and risk for coronary artery disease
Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
Lu, Yingchang, et al. (författare)
New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk.
Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 7
To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
Stancáková, Alena (18)
McKenzie, Colin A. (18)
Chambers, John C. (18)
Kooner, Jaspal S. (18)
Harris, Tamara B (17)
Tayo, Bamidele O. (17)
Chasman, Daniel I. (16)
Cupples, L. Adrienne (16)
Feitosa, Mary F. (16)
Cooper, Richard S. (16)
Ridker, PM (15)
Stancakova, A (15)
Rauramaa, R (15)
Raitakari, Olli T (14)
Gudnason, Vilmundur (14)
Uitterlinden, AG (14)
Kuusisto, Johanna (14)
Scott, Robert A (14)
Chasman, DI (14)
Munroe, Patricia B. (14)
Hayward, Caroline (14)
Harris, TB (14)
Zhao, JH (14)
Zhao, Jing Hua (14)
Zhang, Weihua (14)
Lakka, Timo A. (14)
Umeå universitet (9)
Uppsala universitet (1)
Naturvetenskap (2)