scholarly journals A novel Mendelian randomization method identifies causal relationships between gene expression and low-density lipoprotein cholesterol levels

2019 ◽  
Author(s):  
Adriaan van der Graaf ◽  
Annique Claringbould ◽  
Antoine Rimbert ◽  
Harm-Jan Westra ◽  
Yang Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Complex Traits ◽  
Mendelian Randomization ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Causal Relationships ◽  
Low Density Lipoprotein Cholesterol ◽  
Individual Level

AbstractRobust inference of causal relationships between gene expression and complex traits using Mendelian Randomization (MR) approaches is confounded by pleiotropy and linkage disequilibrium (LD) between gene expression quantitative loci (eQTLs). Here we propose a new MR method, MR-link, that accounts for unobserved pleiotropy and LD by leveraging information from individual-level data. In simulations, MR-link shows false positive rates close to expectation (median 0.05) and high power (up to 0.89), outperforming all other MR methods we tested, even when only one eQTL variant is present. Application of MR-link to low-density lipoprotein cholesterol (LDL-C) measurements in 12,449 individuals and eQTLs summary statistics from whole blood and liver identified 19 genes causally linked to LDL-C. These include the previously functionally validatedSORT1gene, and thePVRL2gene, located in theAPOElocus, for which a causal role in liver was yet unknown. Our results showcase the strength of MR-link for transcriptome-wide causal inferences.

scholarly journals Mendelian randomization while jointly modeling cis genetics identifies causal relationships between gene expression and lipids

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Adriaan van der Graaf ◽  
◽  
Annique Claringbould ◽  
Antoine Rimbert ◽  
Harm-Jan Westra ◽  
...  
Keyword(s):  
Gene Expression ◽  
Complex Traits ◽  
Mendelian Randomization ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Summary Statistics ◽  
Low Density Lipoprotein Cholesterol ◽  
Causal Inferences ◽  
Individual Level ◽  
Level Data

Abstract Inference of causality between gene expression and complex traits using Mendelian randomization (MR) is confounded by pleiotropy and linkage disequilibrium (LD) of gene-expression quantitative trait loci (eQTL). Here, we propose an MR method, MR-link, that accounts for unobserved pleiotropy and LD by leveraging information from individual-level data, even when only one eQTL variant is present. In simulations, MR-link shows false-positive rates close to expectation (median 0.05) and high power (up to 0.89), outperforming all other tested MR methods and coloc. Application of MR-link to low-density lipoprotein cholesterol (LDL-C) measurements in 12,449 individuals with expression and protein QTL summary statistics from blood and liver identifies 25 genes causally linked to LDL-C. These include the known SORT1 and ApoE genes as well as PVRL2, located in the APOE locus, for which a causal role in liver was not known. Our results showcase the strength of MR-link for transcriptome-wide causal inferences.

scholarly journals Comparative Effects of Flaxseed Sources on the Egg ALA Deposition and Hepatic Gene Expression in Hy-Line Brown Hens

Foods ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1663
Author(s):  
Muhammad Suhaib Shahid ◽  
Tausif Raza ◽  
Yuqin Wu ◽  
Mazhar Hussain Mangi ◽  
Wei Nie ◽  
...  
Keyword(s):  
Gene Expression ◽  
Egg Production ◽  
Laying Hens ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Egg Yolk ◽  
Lipoprotein Cholesterol ◽  
Egg Mass ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol

Healthy diets are necessary for both humans and animals, including poultry. These diets contain various nutrients for maintenance and production in laying hens. Therefore, research was undertaken to explore the efficiency of various dietary flaxseed sources on the n-3 deposition in the egg yolk and gene expression in laying hens. Five dietary groups were analyzed, i.e., (i) a corn-based diet with no flaxseed (FS) as a negative control (NC), (ii) a wheat-based diet supplemented with 10% whole FS without multi-carbohydrase enzymes (MCE) as a positive control (PC), (iii) ground FS supplemented with MCE (FS), (iv) extruded flaxseed meal was supplemented with MCE (EFM), (v) flaxseed oil supplemented with MCE (FSO). Results indicated that egg weight was highest in the NC, FS, EFM, and FSO groups as compared to PC in the 12th week. Egg mass was higher in enzyme supplemented groups as compared to the PC group, but lower than NC. In the 12th week, the HDEP (hen day egg production) was highest in the FS and EFM groups as compared to FSO, PC, and NC. The FCR (feed conversion ratio) was better in enzyme supplemented groups as compared to the PC group. Enzyme addition enhanced the egg quality as compared to PC in the 12th week. The HDL-C (high-density lipoprotein cholesterol) was increased, while LDL-C (low-density lipoprotein cholesterol), VLDL-C (very-low-density lipoprotein cholesterol), TC (total cholesterol), and TG (total triglycerides) were reduced in the enzyme supplemented groups as compared to PC and NC. The FSO deposit more n-3 PUFA and docosahexaenoic acid (DHA) in the egg yolk as compared to FS and EFM groups. The expression of ACOX1, LCPT1, FADS1, FADS2, and ELOV2 genes were upregulated, while PPAR-α was downregulated in the FSO group. The LPL mRNA expression was upregulated in the FS, EFM, and FSO groups as compared to the PC and NC groups. It was inferred that FSO with enzymes at 2.5% is cost-effective, improves the hen performances, upregulated the fatty acid metabolism and β-oxidation genes expression, and efficiently deposits optimal n-3 PUFA in the egg as per consumer’s demand.

Low-density lipoprotein cholesterol and risk of gallstone disease: A Mendelian randomization study and meta-analyses

2013 ◽  
Vol 58 (1) ◽  
pp. 126-133 ◽  
Author(s):  
Stefan Stender ◽  
Ruth Frikke-Schmidt ◽  
Marianne Benn ◽  
Børge G. Nordestgaard ◽  
Anne Tybjærg-Hansen
Keyword(s):  
Mendelian Randomization ◽  
Low Density Lipoprotein ◽  
Gallstone Disease ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Meta Analyses

scholarly journals Low-Density Lipoprotein Cholesterol and the Risk of Cancer: A Mendelian Randomization Study

2011 ◽  
Vol 103 (6) ◽  
pp. 508-519 ◽  
Author(s):  
Marianne Benn ◽  
Anne Tybjærg-Hansen ◽  
Stefan Stender ◽  
Ruth Frikke-Schmidt ◽  
Børge G. Nordestgaard
Keyword(s):  
Mendelian Randomization ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Risk Of Cancer
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