Search results for "Mendelian"

Genetic basis of trichome production in Arabidopsis lyrata.

2002

Leaf trichomes may protect plants against herbivorous insects, and may increase tolerance to drought and UV-radiation. The perennial herb Arabidopsis lyrata (Brassicaceae) is polymorphic for trichome production and occurs in a glabrous and trichome-producing form. In addition, there is quantitative variation in trichome density among trichome-producing plants. To examine the genetic basis of glabrousness, we conducted controlled crosses with plants originating from two natural populations in Sweden (one polymorphic for trichome-production, and one consisting of glabrous plants only). In addition, we estimated the heritability of trichome number from parent-offspring regressions for plants o…

2022

This study quantifies the causal effect of birth weight on cardiovascular biomarkers in adulthood using the Cardiovascular Risk in Young Finns Study (YFS). We apply a multivariable Mendelian randomization (MVMR) method that provides a novel approach to improve inference in causal analysis based on a mediation framework. The results show that birth weight is linked to triglyceride levels (β = -0.294; 95% CI [-0.591, 0.003]) but not to low-density lipoprotein (LDL) cholesterol levels (β = 0.007; 95% CI [-0.168, 0.183]). The total effect of birth weight on triglyceride levels is partly offset by a mediation pathway linking birth weight to adult BMI (β = 0.111; 95% CI [-0.013, 0.234]). The nega…

Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

2021

Abstract Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci ass…

Does higher education protect against obesity? Evidence using Mendelian randomization

2017

Objectives. The aim of this explorative study was to examine the effect of education on obesity using Mendelian randomization. Methods. Participants (N = 2011) were from the on- going nationally representative Young Finns Study (YFS) that began in 1980 when six cohorts (aged 30, 33, 36, 39, 42 and 45 in 2007) were recruited. The average value of BMI (kg/m(2)) measurements in 2007 and 2011 and genetic information were linked to comprehensive register based information on the years of education in 2007. We first used a linear regression (Ordinary Least Squares, OLS) to estimate the relationship between education and BMI. To identify a causal relationship, we exploited Mendelian randomization …

P5313The association between coffee and caffeine consumption and renal function: insight from individual-level data, Mendelian randomization, and met…

2019

Abstract Background The reported relationship between coffee intake and renal function is poorly understood. Purpose By applying on two-sample Mendelian randomization (MR) and systematic review and meta-analysis we investigated the association between caffeine and coffee intake with prevalent CKD and markers of renal function. Methods For the individual data analysis we analysed the NHANES data on renal function markers and caffeine intake. MR was implemented by using summary-level data from genome-wide association studies conducted on coffee intake (N=91,462) and kidney function (N=133,413). Inverse variance weighted method (IVW), weighted median-based method, MR-Egger, MR-RAPS, MR-PRESSO …

Stature and long-term labor market outcomes: Evidence using Mendelian randomization.

2017

We use the Young Finns Study (N = ∼2000) on the measured height linked to register-based long-term labor market outcomes. The data contain six age cohorts (ages 3, 6, 9, 12, 15 and 18, in 1980) with the average age of 31.7, in 2001, and with the female share of 54.7. We find that taller people earn higher earnings according to the ordinary least squares (OLS) estimation. The OLS models show that 10 cm of extra height is associated with 13% higher earnings. We use Mendelian randomization, with the genetic score as an instrumental variable (IV) for height to account for potential confounders that are related to socioeconomic background, early life conditions and parental investments, which ar…

Identification and prevention of genotyping errors caused by G-quadruplex- and i-motif-like sequences.

2009

Abstract Background: Reliable PCR amplification of DNA fragments is the prerequisite for most genetic assays. We investigated the impact of G-quadruplex– or i-motif–like sequences on the reliability of PCR-based genetic analyses. Methods: We found the sequence context of a common intronic polymorphism in the MEN1 gene (multiple endocrine neoplasia I) to be the cause of systematic genotyping errors by inducing preferential amplification of one allelic variant [allele dropout (ADO)]. Bioinformatic analyses and pyrosequencing-based allele quantification enabled the identification of the underlying DNA structures. Results: We showed that G-quadruplex– or i-motif–like sequences can reproducibly …

Genetically elevated gamma-glutamyltransferase and Alzheimer's disease

2018

Observational epidemiological evidence supports a linear and independent association between serum gamma-glutamyltransferase (GGT) concentrations and the risk of Alzheimer's disease (AD). However, the causality of this association has not been previously investigated. We sought to assess the causal nature of this association using a Mendelian randomization (MR) approach. Using inverse-variance weighted MR analysis, we assessed the association between GGT and AD using summary statistics for single nucleotide polymorphism (SNP)-AD associations obtained from the International Genomics of Alzheimer's Project of 17,008 individuals with AD and 37,154 controls. We used 26 SNPs significantly associ…

Sex-Specific Differences in the Control of Serum Concentrations of Glycine in Subjects with Metabolic Syndrome and Mendelian Randomization Analysis f…

2020

OBJECTIVES: Glycine is a novel circulating marker for metabolic diseases associated with lower type-2 diabetes and protection against obesity in some studies. Circulating glycine levels are genetically determined under the control of several loci. The locus most strongly associated is the carbamoyl-phosphate synthase I (CPS1). Interestingly, some sex-specific genome-wide association studies (GWAS) showed differences in the effect of the main single nucleotide polymorphisms (SNPs) in this locus on glycine levels (significant sex * CPS1 interactions). However, the potential mechanisms explaining this sex-heterogeneity are unknown. Therefore, our aims were: 1) to analyze whether the sex * CPS1…

The association between coffee and caffeine consumption and renal function: insight from individual-level data, Mendelian randomization, and meta-ana…

2022

IntroductionBy applying on two-sample Mendelian randomization and systematic review and meta-analysis we investigated the association between caffeine and coffee intake with prevalent CKD and markers of renal function.Material and methodsFor the individual data analysis we analysed the NHANES data on renal function markers and caffeine intake. MR was implemented by using summary-level data from the largest ever GWAS conducted on coffee intake (N=91,462) and kidney function.ResultsFinally, we included the data of 18,436 participants, 6.9% had prevalent CKD (based on eGFR). Caffeine intake for general population was 131.1±1.1 mg. The percentage of participants with CKD, by caffeine quartile w…