80 research outputs found
Genetic Differences between the Determinants of Lipid Profile Phenotypes in African and European Americans: The Jackson Heart Study
Genome-wide association analysis in populations of European descent has recently found more than a hundred genetic variants affecting risk for common disease. An open question, however, is how relevant the variants discovered in Europeans are to other populations. To address this problem for cardiovascular phenotypes, we studied a cohort of 4,464 African Americans from the Jackson Heart Study (JHS), in whom we genotyped both a panel of 12 recently discovered genetic variants known to predict lipid profile levels in Europeans and a panel of up to 1,447 ancestry informative markers allowing us to determine the African ancestry proportion of each individual at each position in the genome. Focusing on lipid profilesâHDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), and triglycerides (TG)âwe identified the lipoprotein lipase (LPL) locus as harboring variants that account for interethnic variation in HDL-C and TG. In particular, we identified a novel common variant within LPL that is strongly associated with TG (pâ=â2.7Ă10â6) and explains nearly 1% of the variability in this phenotype, the most of any variant in African Americans to date. Strikingly, the extensively studied âgain-of-functionâ S447X mutation at LPL, which has been hypothesized to be the major determinant of the LPL-TG genetic association and is in trials for human gene therapy, has a significantly diminished strength of biological effect when it is found on a background of African rather than European ancestry. These results suggest that there are other, yet undiscovered variants at the locus that are truly causal (and are in linkage disequilibrium with S447X) or that work synergistically with S447X to modulate TG levels. Finally, we find systematically lower effect sizes for the 12 risk variants discovered in European populations on the African local ancestry background in JHS, highlighting the need for caution in the use of genetic variants for risk assessment across different populations
Determinants of selenium status in healthy adults
<p>Abstract</p> <p>Background</p> <p>Selenium (Se) status in non-deficient subjects is typically assessed by the Se contents of plasma/serum. That pool comprises two functional, specific selenoprotein components and at least one non-functional, non-specific components which respond differently to changes in Se intake. A more informative means of characterizing Se status in non-deficient individuals is needed.</p> <p>Methods</p> <p>Multiple biomarkers of Se status (plasma Se, serum selenoprotein P [SEPP1], plasma glutathione peroxidase activity [GPX3], buccal cell Se, urinary Se) were evaluated in relation to selenoprotein genotypes (GPX1, GPX3, SEPP1, SEP15), dietary Se intake, and parameters of single-carbon metabolism in a cohort of healthy, non-Se-deficient men (n = 106) and women (n = 155).</p> <p>Conclusions</p> <p>Plasma Se concentration was 142.0 ± 23.5 ng/ml, with GPX3 and serum-derived SEPP1 calculated to comprise 20% and 34%, respectively, of that total. The balance, comprised of non-specific components, accounted for virtually all of the interindividual variation in total plasma Se. Buccal cell Se was associated with age and plasma homocysteine (hCys), but not plasma Se. SEPP1 showed a quadratic relationship with body mass index, peaking at BMI 25-30. Urinary Se was greater in women than men, and was associated with metabolic body weight (kg<sup>0.75</sup>), plasma folate, vitamin B<sub>12 </sub>and hCys (negatively). One <it>GPX1 </it>genotype (679T/T) was associated with significantly lower plasma Se levels than other allelic variants. Selenium intake, estimated from food frequency questionnaires, did not predict Se status as indicated by any biomarker. These results show that genotype, methyl-group status and BMI contribute to variation in Se biomarkers in Se-adequate individuals.</p
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Association of apolipoprotein E gene polymorphisms with blood lipids and their interaction with dietary factors
Several candidate genes have been identified in relation to lipid metabolism, and among these, lipoprotein lipase (LPL) and apolipoprotein E (APOE) gene polymorphisms are major sources of genetically determined variation in lipid concentrations. This study investigated the association of two single nucleotide polymorphisms (SNPs) at LPL, seven tagging SNPs at the APOE gene, and a common APOE haplotype (two SNPs) with blood lipids, and examined the interaction of these SNPs with dietary factors.
METHODS:
The population studied for this investigation included 660 individuals from the Prevention of Cancer by Intervention with Selenium (PRECISE) study who supplied baseline data. The findings of the PRECISE study were further replicated using 1238 individuals from the Caerphilly Prospective cohort (CaPS). Dietary intake was assessed using a validated food-frequency questionnaire (FFQ) in PRECISE and a validated semi-quantitative FFQ in the CaPS. Interaction analyses were performed by including the interaction term in the linear regression model adjusted for age, body mass index, sex and country.
RESULTS:
There was no association between dietary factors and blood lipids after Bonferroni correction and adjustment for confounding factors in either cohort. In the PRECISE study, after correction for multiple testing, there was a statistically significant association of the APOE haplotype (rs7412 and rs429358; E2, E3, and E4) and APOE tagSNP rs445925 with total cholesterol (Pâ=â4âĂâ10-â4 and Pâ=â0.003, respectively). Carriers of the E2 allele had lower total cholesterol concentration (5.54â±â0.97 mmol/L) than those with the E3 (5.98â±â1.05 mmol/L) (Pâ=â0.001) and E4 (6.09â±â1.06 mmol/L) (Pâ=â2âĂâ10-â4) alleles. The association of APOE haplotype (E2, E3, and E4) and APOE SNP rs445925 with total cholesterol (Pâ=â2âĂâ10-â6 and Pâ=â3âĂâ10-â4, respectively) was further replicated in the CaPS. Additionally, significant association was found between APOE haplotype and APOE SNP rs445925 with low density lipoprotein cholesterol in CaPS (Pâ=â4âĂâ10-â4 and Pâ=â0.001, respectively). After Bonferroni correction, none of the cohorts showed a statistically significant SNP-diet interaction on lipid outcomes.
CONCLUSION:
In summary, our findings from the two cohorts confirm that genetic variations at the APOE locus influence plasma total cholesterol concentrations, however, the gene-diet interactions on lipids require further investigation in larger cohorts
Measurement of the electron reconstruction efficiency at LHCb
The single electron track-reconstruction efficiency is calibrated using a sample corresponding to 1.3 fbâ1 of pp collision data recorded with the LHCb detector in 2017. This measurement exploits B+â J/Ï(e+eâ)K+ decays, where one of the electrons is fully reconstructed and paired with the kaon, while the other electron is reconstructed using only the information of the vertex detector. Despite this partial reconstruction, kinematic and geometric constraints allow the B meson mass to be reconstructed and the signal to be well separated from backgrounds. This in turn allows the electron reconstruction efficiency to be measured by matching the partial track segment found in the vertex detector to tracks found by LHCb's regular reconstruction algorithms. The agreement between data and simulation is evaluated, and corrections are derived for simulated electrons in bins of kinematics. These correction factors allow LHCb to measure branching fractions involving single electrons with a systematic uncertainty below 1%
Angular Analysis of the B+ -> K*(+)mu(+) mu(-) Decay
We present an angular analysis of the
B
+
â
K
*
+
(
â
K
0
S
Ï
+
)
Ό
+
Ό
â
decay using
9
â
â
fb
â
1
of
p
p
collision data collected with the LHCb experiment. For the first time, the full set of
C
P
-averaged angular observables is measured in intervals of the dimuon invariant mass squared. Local deviations from standard model predictions are observed, similar to those in previous LHCb analyses of the isospin-partner
B
0
â
K
*
0
Ό
+
Ό
â
decay. The global tension is dependent on which effective couplings are considered and on the choice of theory nuisance parameters
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Study of the and states in decays
The decays are studied using a data
set corresponding to an integrated luminosity of 9fb collected with the
LHCb detector in proton-proton collisions between 2011 and 2018. Precise
measurements of the ratios of branching fractions with the intermediate
, and states are reported. The decay
of with is observed for the first time with a significance of 5.1
standard deviations. The mass differences between the ,
and states are measured to be resulting in the
most precise determination of the mass. The width of the
state is found to be below 5.2MeV at 90\% confidence level. The
Breit-Wigner width of the state is measured to be which is inconsistent with zero by 5.5 standard deviations
Search for time-dependent violation in and decays
A search for time-dependent violation of the charge-parity symmetry in and decays is performed at the LHCb experiment using proton-proton collision data recorded from 2015 to 2018 at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 6 fb. The meson is required to originate from a decay, such that its flavour at production is identified by the charge of the accompanying pion. The slope of the time-dependent asymmetry of the decay rates of and mesons into the final states under consideration is measured to be , , where the first uncertainties are statistical and the second are systematic. These results are compatible with the conservation of the charge-parity symmetry at the level of 2 standard deviations and improve the precision by nearly a factor of two
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