250 research outputs found
Reversal of Tetracycline Resistance by Cepharanthine, Cinchonidine, Ellagic Acid and Propyl Gallate in a Multi-drug Resistant Escherichia coli
- Author
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 03/11/2020
- Field of study
Bacterial resistance to antibiotics is an increasing threat to global healthcare systems. We therefore sought compounds with potential to reverse antibiotic resistance in a clinically relevant multi-drug resistant isolate of Escherichia coli (NCTC 13400). 200 natural compounds with a history of either safe oral use in man, or as a component of a traditional herb or medicine, were screened. Four compounds; ellagic acid, propyl gallate, cinchonidine and cepharanthine, lowered the minimum inhibitory concentrations (MICs) of tetracycline, chloramphenicol and tobramycin by up to fourfold, and when combined up to eightfold. These compounds had no impact on the MICs of ampicillin, erythromycin or trimethoprim. Mechanistic studies revealed that while cepharanthine potently suppressed efflux of the marker Nile red from bacterial cells, the other hit compounds slowed cellular accumulation of this marker, and/or slowed bacterial growth in the absence of antibiotic. Although cepharanthine showed some toxicity in a cultured HEK-293 mammalian cell-line model, the other hit compounds exhibited no toxicity at concentrations where they are active against E. coli NCTC 13400. The results suggest that phytochemicals with capacity to reverse antibiotic resistance may be more common in traditional medicines than previously appreciated, and may offer useful scaffolds for the development of antibiotic-sensitising drugs
Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV
- Author
- Aad G
- Abbott B
- Abdallah J
- Abdelalim AA
- Abdesselam A
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- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/03/2013
- Field of study
The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration
Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector
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- Zimmermann R
- Zimmermann S
- Zimmermann S
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- Zmouchko VV
- Zobernig G
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- Zsenei A
- zur Nedden M
- Zutshi V
- Zwalinski L
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 31/12/2010
- Field of study
The inclusive and dijet production cross-sections have been measured for jets
containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass
energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The
measurements use data corresponding to an integrated luminosity of 34 pb^-1.
The b-jets are identified using either a lifetime-based method, where secondary
decay vertices of b-hadrons in jets are reconstructed using information from
the tracking detectors, or a muon-based method where the presence of a muon is
used to identify semileptonic decays of b-hadrons inside jets. The inclusive
b-jet cross-section is measured as a function of transverse momentum in the
range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet
cross-section is measured as a function of the dijet invariant mass in the
range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets
and the angular variable chi in two dijet mass regions. The results are
compared with next-to-leading-order QCD predictions. Good agreement is observed
between the measured cross-sections and the predictions obtained using POWHEG +
Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet
cross-section. However, it does not reproduce the measured inclusive
cross-section well, particularly for central b-jets with large transverse
momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final
version published in European Physical Journal
Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations : A transethnic genome-wide meta-analysis
- Author
- Abecasis G
- Afaq S
- Alizadeh BZ
- Aung T
- Barroso I
- Bertoni AG
- Blüher M
- Boehnke M
- Bonnefond A
- Boomsma DI
- Bornstein SR
- Bottinger EP
- Böttcher Y
- Campbell H
- Carlson OD
- Chambers JC
- Chang L-C
- Chasman DI
- Chen C-H
- Chen P
- Chen W-M
- Chen Y-DI
- Chen Y-T
- Cheng C-Y
- Cho YS
- Chu AY
- Cucca F
- de Geus EJC
- Deloukas P
- Dupuis J
- Egan J
- Elks CE
- EPIC-CVD Consortium
- EPIC-InterAct Consortium
- Evans DS
- Evans MK
- Fan Q
- Ferrucci L
- Florez JC
- Fornage M
- Friedlander Y
- Froguel P
- Garvey WT
- Gieger C
- Giulianini F
- Go MJ
- Goel A
- Goodarzi MO
- Grallert H
- Groop L
- Gross MD
- Guo X
- Hamsten A
- Harris TB
- Hartman CA
- Hayward C
- Heng C-K
- Herder C
- Hingorani AD
- Hivert M-F
- Hong J
- Hottenga J-J
- Hovingh GK
- Hsiung CA
- Hu Y
- Huang J
- Igase M
- Ingelsson E
- Isono M
- Jackson AU
- Jia Y
- Jula A
- Kabagambe EK
- Kanoni S
- Kato N
- Katsuya T
- Khor C-C
- Kiess W
- Kim B-J
- Kim YJ
- Kivimaki M
- Kleber ME
- Koh W-P
- Kohara K
- Kooner JS
- Kovacs P
- Kuh D
- Kumari M
- Kuusisto J
- Körner A
- Laakso M
- Ladenvall C
- Langenberg C
- Lecoeur C
- Lee J
- Lee W-J
- Lehne B
- Leong A
- Li H
- Li M
- Lifelines Cohort Study
- Lim S-H
- Lin X
- Liu C-T
- Liu J
- Liu Y
- Lobbens S
- Loos RJF
- Lu Y
- Luan J
- Lyssenko V
- Magnusson PKE
- Mahajan A
- Martinez Larrad MT
- Maruthur NM
- Marzi C
- McCarthy MI
- Meigs JB
- Meitinger T
- Miki T
- Miljkovic I
- Moon S
- Morris AP
- Mulas A
- März W
- Müller G
- Müller-Nurasyid M
- Nagaraja R
- Nalls MA
- Nauck M
- Navarro P
- Njølstad I
- Nolte IM
- Oldehinkel AJ
- Ong KK
- Palmer CNA
- Pankow JS
- Pedersen NL
- Pereira MA
- Peters A
- Podmore C
- Polasek O
- Porneala BC
- Prokopenko I
- Radke D
- Ramos PS
- Rasmussen-Torvik L
- Rathmann W
- Rich SS
- Ridker PM
- Roberts DJ
- Robertson NR
- Roden M
- Rose LM
- Rotter JI
- Roussel R
- Rudan I
- Rybin DV
- Sabanayagam C
- Sale M
- Saleheen D
- Salo P
- Saltevo J
- Sanna S
- Schwarz PE
- Scott RA
- Scott WR
- Selvin E
- Sennblad B
- Serrano Ríos M
- Sharp SJ
- Sheu WHH
- Shi Y
- Sim X
- Siscovick DS
- Sladek R
- Snieder H
- Soranzo N
- Spector TD
- Stram DO
- Strauch K
- Strawbridge RJ
- Stumvoll M
- Sun L
- Swertz M
- Tabara Y
- Tai E-S
- Tajuddin SM
- Takeuchi F
- Tan SP
- Tanaka T
- Taylor KD
- Teo Y-Y
- Tham YC
- Tuomilehto J
- Tönjes A
- van Dam RM
- van der Most PJ
- van Iperen EPA
- Van Vliet-Ostaptchouk JV
- Wang X
- Wareham NJ
- Watkins H
- Wheeler E
- Willemsen G
- Wilsgaard T
- Wilson JF
- Wilson JG
- Wolffenbuttel BHR
- Wong A
- Wong TY
- Wu J-Y
- Yao J
- Yengo L
- Yuan J-M
- Zhang W
- Zhao W
- Zonderman AB
- Publication venue
- Publication date
- 01/01/2017
- Field of study
Background Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes. Methods & findings Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04-1.06, per HbA1c-raising allele, p = 3 x 10-29); whereas GS-E was not (OR = 1.00, 95% CI 0.99-1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66-0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38-0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI0.55-0.74) of African American adults with T2Dto remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants. Conclusions As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses.Peer reviewe
Measurement of the cross-section for b-jets produced in association with a Z boson at root s=7 TeV with the ATLAS detector ATLAS Collaboration
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- Ammosov VV
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- Yilmaz M
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- Zaidan R
- Zaitsev AM
- Zajacova Z
- Zalite YK
- Zanello L
- Zarzhitsky P
- Zaytsev A
- Zeitnitz C
- Zeller M
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- Zemla A
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- Zenin O
- Zenis T
- Zenonos Z
- Zenz S
- Zerwas D
- Zhan Z
- Zhang D
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- Zhang Z
- Zhao L
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- Zhao Z
- Zhemchugov A
- Zheng S
- Zhong J
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- Zhu CG
- Zhu H
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- Zhu Y
- Zhuang X
- Zhuravlov V
- Zieminska D
- Zimmermann R
- Zimmermann S
- Zimmermann S
- Ziolkowski M
- Zitoun R
- Zivkovic L
- Zmouchko VV
- Zobernig G
- Zoccoli A
- Zolnierowski Y
- Zsenei A
- zur Nedden M
- Zutshi V
- Zwalinski L
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2011
- Field of study
A measurement is presented of the inclusive cross-section for b-jet production in association with a Z boson in pp collisions at a centre-of-mass energy of root s = 7 TeV. The analysis uses the data sample collected by the ATLAS experiment in 2010, corresponding to an integrated luminosity of approximately 36 pb(-1). The event selection requires a Z boson decaying into high P-T electrons or muons, and at least one b-jet, identified by its displaced vertex, with transverse momentum p(T) > 25 GeV and rapidity vertical bar y vertical bar < 2.1. After subtraction of background processes, the yield is extracted from the vertex mass distribution of the candidate b-jets. The ratio of this cross-section to the inclusive Z cross-section (the average number of b-jets per Z event) is also measured. Both results are found to be in good agreement with perturbative QCD predictions at next-to-leading order
Measurement of charged-particle event shape variables in inclusive root(s)=7 TeV proton-proton interactions with the ATLAS detector
- Author
- Aad G
- Abbott B
- Abdallah J
- Abdelalim AA
- Abdesselam A
- Abdinov O
- Abi B
- Abolins M
- Abramowicz H
- Abreu H
- Acerbi E
- Acharya BS
- Ackers M
- Adams DL
- Addy TN
- Adelman J
- Aderholz M
- Adomeit S
- Adragna P
- Adye T
- Aefsky S
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- Publication venue
- Publication date
- 01/12/2010
- Field of study
The measurement of charged-particle event shape variables is presented in inclusive inelastic pp collisions at a center-of-mass energy of 7 TeV using the ATLAS detector at the LHC. The observables studied are the transverse thrust, thrust minor, and transverse sphericity, each defined using the final-state charged particles' momentum components perpendicular to the beam direction. Events with at least six charged particles are selected by a minimum-bias trigger. In addition to the differential distributions, the evolution of each event shape variable as a function of the leading charged-particle transverse momentum, charged-particle multiplicity, and summed transverse momentum is presented. Predictions from several Monte Carlo models show significant deviations from data
Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes
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- Zimanova J
- Zimmerman R
- Zinman B
- Śmiałowski A
- Publication venue
- 'Massachusetts Medical Society'
- Publication date
- 01/01/2015
- Field of study
BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events
Combination of searches for heavy spin-1 resonances using 139 fb−1 of proton-proton collision data at s = 13 TeV with the ATLAS detector
- Author
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- Zhao T
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- Zhao Z
- Zhemchugov A
- Zheng J
- Zheng K
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- Zimine NI
- Zinsser J
- Ziolkowski M
- Zoccoli A
- Zoch K
- Zorbas TG
- Zormpa O
- Zou W
- Zwalinski L
- Åkesson TPA
- Öncel ÖO
- Ženiš T
- Živković L
- Publication venue
- Springer Nature
- Publication date
- 19/04/2024
- Field of study
A combination of searches for new heavy spin-1 resonances decaying into different pairings of W, Z, or Higgs bosons, as well as directly into leptons or quarks, is presented. The data sample used corresponds to 139 fb−1 of proton-proton collisions at
= 13 TeV collected during 2015–2018 with the ATLAS detector at the CERN Large Hadron Collider. Analyses selecting quark pairs (qq, bb,
, and tb) or third-generation leptons (τν and ττ) are included in this kind of combination for the first time. A simplified model predicting a spin-1 heavy vector-boson triplet is used. Cross-section limits are set at the 95% confidence level and are compared with predictions for the benchmark model. These limits are also expressed in terms of constraints on couplings of the heavy vector-boson triplet to quarks, leptons, and the Higgs boson. The complementarity of the various analyses increases the sensitivity to new physics, and the resulting constraints are stronger than those from any individual analysis considered. The data exclude a heavy vector-boson triplet with mass below 5.8 TeV in a weakly coupled scenario, below 4.4 TeV in a strongly coupled scenario, and up to 1.5 TeV in the case of production via vector-boson fusion
A multifunctional thermophilic glycoside hydrolase from Caldicellulosiruptor owensensis with potential applications in production of biofuels and biochemicals
- Author
- A Bai
- A Bhalla
- AR Joo
- AR Park
- AR Park
- AV Gusakov
- B Lauro Di
- C Divne
- C Kim
- C Uchima
- C-Y Huang
- DL Zechel
- ES Ji
- F Kong
- F Segato
- GL Miller
- H Mallek-Fakhfakh
- Hong Su
- I Roy
- IU Haq
- J Rouvinen
- JD Bok
- KM Lee
- KM Lee
- L Gao
- L Li
- L Li
- M Garvey
- MK Tiwari
- MM Bradford
- MR Green
- MW Bauer
- N Hassan
- N Parry
- O Juajun
- PS Panesar
- R Brunecky
- R Gupta
- S Mi
- SE Blumer-Schuette
- SE Blumer-Schuette
- SE Blumer-Schuette
- SE Blumer-Schuette
- Shuofu Mi
- SL Arreola
- SS Jagtap
- ST Merino
- T Haider
- TT Nguyen
- V Reyes-Ortiz
- W Qiao
- WY Jeng
- X Li
- X Peng
- Xiaowei Peng
- Y Bhatia
- Yejun Han
- YHP Zhang
- ZZ Zou
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Gene-centric meta-analysis of lipid traits in African, East Asian and Hispanic populations.
- Author
- Anand SS
- Asselbergs FW
- Ballantyne CM
- Becker DM
- Borecki IB
- Buxbaum SG
- Castillo BA
- Chen F
- Chen WM
- Chen YD
- Cupples LA
- Cushman M
- Drenos F
- Duan Y
- Duggan D
- Elbers CC
- Evans MK
- Fernandes JK
- Ferwerda B
- Fornage M
- Garcia M
- Garvey WT
- Glazer N
- Gomez F
- Guo Y
- Hakonarson H
- Halder I
- Harris TB
- Hegele RA
- Howard VJ
- Kamboh MI
- Kathiresan S
- Keating BJ
- Keller MF
- Kooperberg C
- Kritchevsky SB
- LaCroix A
- Lanktree MB
- Li YR
- Liu K
- Liu Y
- Musunuru K
- Nalls MA
- Newman AB
- Onland-Moret NC
- Ordovas J
- Peter I
- Post W
- Psaty B
- Rader DJ
- Redline S
- Reiner AP
- Reis SE
- Rich SS
- Rotter JI
- Sale MM
- Saxena R
- Schreiner PJ
- Sivapalaratnam S
- Taylor HA
- Tragante V
- Tsai MY
- van Iperen EP
- Volcik KA
- Wang X
- Wilson JG
- Wojczynski MK
- Yanek LR
- Yusuf S
- Zonderland AB
- Publication venue
- Publication date
- 01/01/2012
- Field of study
Meta-analyses of European populations has successfully identified genetic variants in over 100 loci associated with lipid levels, but our knowledge in other ethnicities remains limited. To address this, we performed dense genotyping of ∼2,000 candidate genes in 7,657 African Americans, 1,315 Hispanics and 841 East Asians, using the IBC array, a custom ∼50,000 SNP genotyping array. Meta-analyses confirmed 16 lipid loci previously established in European populations at genome-wide significance level, and found multiple independent association signals within these lipid loci. Initial discovery and in silico follow-up in 7,000 additional African American samples, confirmed two novel loci: rs5030359 within ICAM1 is associated with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (p = 8.8×10(-7) and p = 1.5×10(-6) respectively) and a nonsense mutation rs3211938 within CD36 is associated with high-density lipoprotein cholesterol (HDL-C) levels (p = 13.5×10(-12)). The rs3211938-G allele, which is nearly absent in European and Asian populations, has been previously found to be associated with CD36 deficiency and shows a signature of selection in Africans and African Americans. Finally, we have evaluated the effect of SNPs established in European populations on lipid levels in multi-ethnic populations and show that most known lipid association signals span across ethnicities. However, differences between populations, especially differences in allele frequency, can be leveraged to identify novel signals, as shown by the discovery of ICAM1 and CD36 in the current report
- …