Dataset Information

A genome-wide association study of monozygotic twin-pairs suggests a locus related to variability of serum high-density lipoprotein cholesterol.

ABSTRACT: Genome-wide association analysis on monozygotic twin-pairs offers a route to discovery of gene environment interactions through testing for variability loci associated with sensitivity to individual environment/lifestyle. We present a genome-wide scan of loci associated with intra-pair differences in serum lipid and apolipoprotein levels. We report data for 1,720 monozygotic female twin-pairs from GenomEUtwin project with 2.5 million SNPs, imputed or genotyped, and measured serum lipid fractions for both twins. We found one locus associated with intra-pair differences in high-density lipoprotein cholesterol, rs2483058 in an intron of SRGAP2, where twins carrying the C allele are more sensitive to environmental factors(P=3.98 x 10-8). We followed up the association in further genotyped monozygotic twins (N= 1,261),which showed a moderate association for the variant (P= 0.200, same direction of an effect). In addition,we report a new association on the level of apolipoprotein A-ll (P= 4.03 x 1 o-8).

SUBMITTER: Surakka I

PROVIDER: S-EPMC4333218 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A genome-wide association study of monozygotic twin-pairs suggests a locus related to variability of serum high-density lipoprotein cholesterol.

Surakka Ida I Whitfield John B JB Perola Markus M Visscher Peter M PM Montgomery Grant W GW Falchi Mario M Willemsen Gonneke G de Geus Eco J C EJ Magnusson Patrik K E PK Christensen Kaare K Sørensen Thorkild I A TI Pietiläinen Kirsi H KH Rantanen Taina T Silander Kaisa K Widén Elisabeth E Muilu Juha J Rahman Iffat I Liljedahl Ulrika U Syvänen Ann-Christine AC Palotie Aarno A Kaprio Jaakko J Kyvik Kirsten O KO Pedersen Nancy L NL Boomsma Dorret I DI Spector Tim T Martin Nicholas G NG Ripatti Samuli S Peltonen Leena L

Twin research and human genetics : the official journal of the International Society for Twin Studies 20121003 6

Genome-wide association analysis on monozygotic twin-pairs offers a route to discovery of gene environment interactions through testing for variability loci associated with sensitivity to individual environment/lifestyle. We present a genome-wide scan of loci associated with intra-pair differences in serum lipid and apolipoprotein levels. We report data for 1,720 monozygotic female twin-pairs from GenomEUtwin project with 2.5 million SNPs, imputed or genotyped, and measured serum lipid fractions ...[more]

PMID: 23031429

Similar Datasets

Project description:Background and objectiveKlotho is a protein that is closely related to human aging. Soluble Klotho (S-Klotho) is a circulating protein, and its level decreases in response to systemic inflammation. The relationship between the platelet/high-density lipoprotein cholesterol ratio (PHR), an emerging inflammatory index, and S-Klotho concentrations is still unclear. In addition, the mean platelet volume has been confirmed to have a significant negative association with S-Klotho concentrations, but the relationship between the platelet count (PC) and S-Klotho concentrations has not yet been reported.MethodsData from individuals who participated in the National Health and Nutrition Examination Survey (NHANES) during the five cycles from 2007 to 2016 were retrieved for analysis. Linear regression, two-piecewise linear regression, and restricted cubic spline (RCS) methods were used to analyze the associations of the PHR index and its components with S-Klotho concentrations. In addition, subgroup analysis and effect modification tests were conducted.ResultsA total of 11,123 participants (5463 men (48.17%)), with an average age of 56.2 years, were included. After full adjustment, the S-Klotho levels of participants in the highest quartile group of PHR (β: -51.19, 95% CI: -75.41 to -26.97, P < 0.001) and the highest quartile group of PC (β: -72.34, 95% CI: -93.32 to -51.37, P < 0.0001) were significantly lower than those in their respective lowest quartile groups, and a significant downward trend was presented among the four groups (P for trend < 0.05, respectively). However, high-density lipoprotein cholesterol (HDL-C) concentrations were not significantly associated with S-Klotho concentrations. RCS revealed that the PHR and PC were nonlinearly associated with S-Klotho concentrations; two-piecewise linear regression revealed that the inflection points were 175.269 and 152, respectively, and that these associations slightly weakened after the inflection point. According to the subgroup analysis, liver disease status enhanced the association between the PC and S-Klotho concentrations.ConclusionsBoth the PHR and PC were significantly negatively associated with S-Klotho concentrations, and these associations were nonlinear. There was no significant association between HDL-C and S-Klotho concentrations. Liver disease status enhances the negative association between the PC and S-Klotho concentrations, and the specific mechanism deserves further exploration.

Dataset Information

A genome-wide association study of monozygotic twin-pairs suggests a locus related to variability of serum high-density lipoprotein cholesterol.

Publications

A genome-wide association study of monozygotic twin-pairs suggests a locus related to variability of serum high-density lipoprotein cholesterol.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets