Dataset Information

Blood lipids and colorectal polyps: testing an etiologic hypothesis using phenotypic measurements and Mendelian randomization.

ABSTRACT: Studies linking cholesterol levels to the development of colorectal neoplasia are inconsistent, and Mendelian randomization has been suggested as a way to help avoid problems with confounding and reverse causation.We genotyped individuals who received a colonoscopy at Group Health (1998-2007) for 96 of 102 single-nucleotide polymorphisms identified by the Global Lipids Genetics Consortium. Participants included 139 advanced adenoma cases, 518 non-advanced adenoma cases, 380 non-adenomatous polyp cases, and 754 polyp-free controls. All had at least one available pre-colonoscopy lipid measurement from electronic records maintained by Group Health.Advanced adenoma cases were more likely than controls to have higher pre-colonoscopy zenith low-density lipoprotein (LDL), triglycerides (TG), and total cholesterol (TC) (odds ratio, OR per 20 mg/dL LDL increase: 1.16, 95 % confidence interval, CI 1.03-1.30; per 40 mg/dL TG increase: 1.09, 1.03-1.16; and per 20 mg/dL TC increase: 1.09, 1.02-1.18). For these traits, genotype-polyp ORs using weighted allele scores were not statistically significant (OR per increase in score scaled to a 20 mg/dL LDL increase: 1.17, 0.78-1.75; a 40 mg/dL TG increase: 1.12, 0.91-1.38; a 20 mg/dL TC increase: 0.99, 0.71-1.38).Cholesterol levels may be associated with advanced adenomas, but larger studies are warranted to determine whether this association can be attributed to genetics.

SUBMITTER: Passarelli MN

PROVIDER: S-EPMC4334709 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Blood lipids and colorectal polyps: testing an etiologic hypothesis using phenotypic measurements and Mendelian randomization.

Passarelli Michael N MN Newcomb Polly A PA Makar Karen W KW Burnett-Hartman Andrea N AN Potter John D JD Upton Melissa P MP Zhu Lee-Ching LC Rosenfeld Michael E ME Schwartz Stephen M SM Rutter Carolyn M CM

Cancer causes & control : CCC 20150125 3

<h4>Purpose</h4>Studies linking cholesterol levels to the development of colorectal neoplasia are inconsistent, and Mendelian randomization has been suggested as a way to help avoid problems with confounding and reverse causation.<h4>Methods</h4>We genotyped individuals who received a colonoscopy at Group Health (1998-2007) for 96 of 102 single-nucleotide polymorphisms identified by the Global Lipids Genetics Consortium. Participants included 139 advanced adenoma cases, 518 non-advanced adenoma ...[more]

PMID: 25618792

Similar Datasets

Project description:IntroductionMigraine, a prevalent headache disorder with unclear mechanisms and limited treatments, may be influenced by dyslipidemia and genetic factors. Statins and emerging lipid-modifying agents show potential but lack evidence for migraine management. Mendelian Randomization analysis offers insights into causal relationships and therapeutic targets. This study aims to explore genetically predicted lipid traits, drug targets, and their association with migraine risk.MethodWe conducted Mendelian randomization (MR) analyses utilizing genetic variants associated with lipid traits and variants in genes encoding the protein targets of various classes of lipid-lowering drugs. The specific drug classes investigated included HMGCR, PCSK9, NPC1L1, ABCG5/ABCG8, LDLR, LPL, ANGPTL3, APOB, CETP, and APOC3. To determine the effects on migraine risk, we meta-analyzed MR estimates for regional variants using data from two large sample sets. The genetic variants were weighted based on their associations with specific lipid traits, such as low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), Apolipoprotein A1, and Apolipoprotein B. To obtain association weights, we utilized data from lipid genetics consortia. For lipid-modifying drug targets that exhibited suggestive significance, we further employed expression quantitative trait locus (eQTL) data. Additionally, we performed colocalization analysis to assess genetic confounding.ResultThe use of genetic proxies for HMGCR inhibition demonstrated a significant association with a decreased risk of migraine in the FinnGen dataset (OR = 0.64, 95% CI: 0.46-0.88, p = 0.0006) and a nearly significant association in the Choquet dataset (OR = 0.78, 95% CI: 0.60-1.01, p = 0.06). When pooling the estimates, the overall effect size showed a reduced risk of migraine (OR = 0.73, 95% CI: 0.60-0.89, p = 0.0016). Similarly, genetic mimicry of LPL enhancement was associated with a lower risk of migraine in the FinnGen dataset (OR = 0.82, 95% CI: 0.69-0.96, p = 0.01) and the Choquet dataset (OR = 0.91, 95% CI: 0.83-0.99, p = 0.03). Pooling the estimates showed a consistent effect size (OR = 0.89, 95% CI: 0.83-0.96, p = 0.002). Sensitivity analyses yielded no statistically significant evidence of bias arising from pleiotropy or genetic confounding.ConclusionIn the study, it was observed that among the 10 lipid-lowering drug targets investigated, LPL and HMGCR showed significant associations with migraine risk. These findings indicate that LPL and HMGCR have the potential to serve as candidate drug targets for the treatment or prevention of migraines.

Dataset Information

Blood lipids and colorectal polyps: testing an etiologic hypothesis using phenotypic measurements and Mendelian randomization.

Publications

Blood lipids and colorectal polyps: testing an etiologic hypothesis using phenotypic measurements and Mendelian randomization.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets