FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4210743633> ?p ?o ?g. }

• W4210743633 endingPage "252" @default.
• W4210743633 startingPage "240" @default.
• W4210743633 abstract "Body mass index (BMI) is a complex disease risk factor known to be influenced by genes acting via both metabolic pathways and appetite regulation. In this study, we aimed to gain insight into the phenotypic consequences of BMI-associated genetic variants, which may be mediated by their expression in different tissues. First, we harnessed meta-analyzed gene expression datasets derived from subcutaneous adipose (n = 1257) and brain (n = 1194) tissue to identify 86 and 140 loci, respectively, which provided evidence of genetic colocalization with BMI. These two sets of tissue-partitioned loci had differential effects with respect to waist-to-hip ratio, suggesting that the way they influence fat distribution might vary despite their having very similar average magnitudes of effect on BMI itself (adipose = 0.0148 and brain = 0.0149 standard deviation change in BMI per effect allele). For instance, BMI-associated variants colocalized with TBX15 expression in adipose tissue (posterior probability [PPA] = 0.97), but not when we used TBX15 expression data derived from brain tissue (PPA = 0.04) This gene putatively influences BMI via its role in skeletal development. Conversely, there were loci where BMI-associated variants provided evidence of colocalization with gene expression in brain tissue (e.g., NEGR1, PPA = 0.93), but not when we used data derived from adipose tissue, suggesting that these genes might be more likely to influence BMI via energy balance. Leveraging these tissue-partitioned variant sets through a multivariable Mendelian randomization framework provided strong evidence that the brain-tissue-derived variants are predominantly responsible for driving the genetically predicted effects of BMI on cardiovascular-disease endpoints (e.g., coronary artery disease: odds ratio = 1.05, 95% confidence interval = 1.04–1.07, p = 4.67 × 10−14). In contrast, our analyses suggested that the adipose tissue variants might predominantly be responsible for the underlying relationship between BMI and measures of cardiac function, such as left ventricular stroke volume (beta = 0.21, 95% confidence interval = 0.09–0.32, p = 6.43 × 10−4)." @default.
• W4210743633 created "2022-02-08" @default.
• W4210743633 creator A5006613674 @default.
• W4210743633 creator A5015814169 @default.
• W4210743633 creator A5023002920 @default.
• W4210743633 creator A5024485850 @default.
• W4210743633 creator A5043633854 @default.
• W4210743633 creator A5076124471 @default.
• W4210743633 creator A5086818852 @default.
• W4210743633 date "2022-02-01" @default.
• W4210743633 modified "2023-10-16" @default.
• W4210743633 title "Harnessing tissue-specific genetic variation to dissect putative causal pathways between body mass index and cardiometabolic phenotypes" @default.
• W4210743633 cites W1503357410 @default.
• W4210743633 cites W1512875938 @default.
• W4210743633 cites W1905058580 @default.
• W4210743633 cites W1962159122 @default.
• W4210743633 cites W1970972077 @default.
• W4210743633 cites W1974256272 @default.
• W4210743633 cites W1976844911 @default.
• W4210743633 cites W1976938970 @default.
• W4210743633 cites W1981770302 @default.
• W4210743633 cites W1982804770 @default.
• W4210743633 cites W1986147207 @default.
• W4210743633 cites W1999911866 @default.
• W4210743633 cites W2002153387 @default.
• W4210743633 cites W2005648153 @default.
• W4210743633 cites W2017138237 @default.
• W4210743633 cites W2019232525 @default.
• W4210743633 cites W2039153962 @default.
• W4210743633 cites W2042082983 @default.
• W4210743633 cites W2042459714 @default.
• W4210743633 cites W2044660398 @default.
• W4210743633 cites W2045017910 @default.
• W4210743633 cites W2047783882 @default.
• W4210743633 cites W2050259739 @default.
• W4210743633 cites W2051539480 @default.
• W4210743633 cites W2060319981 @default.
• W4210743633 cites W2064481541 @default.
• W4210743633 cites W2069022895 @default.
• W4210743633 cites W2073836327 @default.
• W4210743633 cites W2094173172 @default.
• W4210743633 cites W2098560069 @default.
• W4210743633 cites W2102311237 @default.
• W4210743633 cites W2103783427 @default.
• W4210743633 cites W2106036991 @default.
• W4210743633 cites W2116908385 @default.
• W4210743633 cites W2118227252 @default.
• W4210743633 cites W2127768736 @default.
• W4210743633 cites W2129006713 @default.
• W4210743633 cites W2129150286 @default.
• W4210743633 cites W2132596222 @default.
• W4210743633 cites W2134113528 @default.
• W4210743633 cites W2140886368 @default.
• W4210743633 cites W2147311167 @default.
• W4210743633 cites W2147774366 @default.
• W4210743633 cites W2147945544 @default.
• W4210743633 cites W2150806217 @default.
• W4210743633 cites W2156271459 @default.
• W4210743633 cites W2161633633 @default.
• W4210743633 cites W2161649767 @default.
• W4210743633 cites W2163144326 @default.
• W4210743633 cites W2238851414 @default.
• W4210743633 cites W2328393125 @default.
• W4210743633 cites W2345313795 @default.
• W4210743633 cites W2520048741 @default.
• W4210743633 cites W2523961905 @default.
• W4210743633 cites W2526546796 @default.
• W4210743633 cites W2729336372 @default.
• W4210743633 cites W2735339162 @default.
• W4210743633 cites W2750529576 @default.
• W4210743633 cites W2761275051 @default.
• W4210743633 cites W2762869502 @default.
• W4210743633 cites W2770092353 @default.
• W4210743633 cites W2770598799 @default.
• W4210743633 cites W2789305195 @default.
• W4210743633 cites W2804452225 @default.
• W4210743633 cites W2805909874 @default.
• W4210743633 cites W2807298064 @default.
• W4210743633 cites W2884743521 @default.
• W4210743633 cites W2888019335 @default.
• W4210743633 cites W2891812515 @default.
• W4210743633 cites W2899836172 @default.
• W4210743633 cites W2908739400 @default.
• W4210743633 cites W2945149264 @default.
• W4210743633 cites W2945528435 @default.
• W4210743633 cites W2949275660 @default.
• W4210743633 cites W2949785910 @default.
• W4210743633 cites W2950769483 @default.
• W4210743633 cites W2951804967 @default.
• W4210743633 cites W2952883732 @default.
• W4210743633 cites W2953318457 @default.
• W4210743633 cites W2954236080 @default.
• W4210743633 cites W2975505463 @default.
• W4210743633 cites W2977182596 @default.
• W4210743633 cites W2999230481 @default.
• W4210743633 cites W3001525769 @default.
• W4210743633 cites W3008983522 @default.
• W4210743633 cites W3011942165 @default.

• next