New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475,000 Individuals

Background - Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association. Methods and Results - Here, we augment the sample with 140 886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, ≈475 000), and the other in the subset of individuals of European descent (≈423 000). Twenty-one SNVs were genome-wide significant (P<5×10-8) for BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP), rs7437940 (AFAP1), rs13303 (missense, STAB1), and rs1055144 (7p15.2). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, SYNPO2L) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at DBH) was genome-wide significant. Conclusions - We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol- increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels

Contribution of common non-synonymous variants in <em>PCSK1</em> to body mass index variation and risk of obesity: A systematic review and meta-analysis with evidence from up to 331 175 individuals.

Polymorphisms rs6232 and rs6234/rs6235 in PCSK1 have been associated with extreme obesity [e.g. body mass index (BMI) ≥ 40 kg/m(2)], but their contribution to common obesity (BMI ≥ 30 kg/m(2)) and BMI variation in a multi-ethnic context is unclear. To fill this gap, we collected phenotypic and genetic data in up to 331 175 individuals from diverse ethnic groups. This process involved a systematic review of the literature in PubMed, Web of Science, Embase and the NIH GWAS catalog complemented by data extraction from pre-existing GWAS or custom-arrays in consortia and single studies. We employed recently developed global meta-analytic random-effects methods to calculate summary odds ratios (OR) and 95% confidence intervals (CIs) or beta estimates and standard errors (SE) for the obesity status and BMI analyses, respectively. Significant associations were found with binary obesity status for rs6232 (OR = 1.15, 95% CI 1.06-1.24, P = 6.08 × 10(-6)) and rs6234/rs6235 (OR = 1.07, 95% CI 1.04-1.10, P = 3.00 × 10(-7)). Similarly, significant associations were found with continuous BMI for rs6232 (β = 0.03, 95% CI 0.00-0.07; P = 0.047) and rs6234/rs6235 (β = 0.02, 95% CI 0.00-0.03; P = 5.57 × 10(-4)). Ethnicity, age and study ascertainment significantly modulated the association of PCSK1 polymorphisms with obesity. In summary, we demonstrate evidence that common gene variation in PCSK1 contributes to BMI variation and susceptibility to common obesity in the largest known meta-analysis published to date in genetic epidemiology

A Very High Momentum Particle Identification Detector

A new detector concept has been investigated to extend the capabilities of heavy-ion collider experiments, represented here through the ALICE detector, in the high transverse momentum (pT region. The resulting Very High Momentum Particle Identification Detector (VHMPID) performs charged hadron identification on a track-by-track basis in the 5 GeV/c &lt; p &lt; 25 GeV/c momentum range and provides heavy-ion experiments with new opportunities to study parton-medium interactions at RHIC and LHC energies, where the creation of deconfined quark-gluon matter has been established. The detector is based on novel advances to the pressurized gaseous ring imaging Cherenkov (RICH) concept, which yield a very compact, high resolution addition to existing heavy-ion experiments. We conclude that in order for the device to yield statistically significant results not only for single particle measurements, but also for di-hadron and jet-tagged correlation studies, it has to cover contiguously up to 30% of a central barrel detector in radial direction. This will allow, for the first time, identified charged hadron measurements in jets. In this paper we summarize the physics motivations for such a device, as well as its conceptual design, layout, and integration into ALICE.1295DE-FG02-07ER41521; DOE; National Research Foundation of Korea; NRF; National Research Foundation of Korea; NSF-PHY-0968903; NSF; National Research Foundation of Korea; NSF-PHY-1305280; NSF; National Research Foundation of Korea(2006) J. Phys. G, 32, p. 1295Sapeta, S., Wiedemann, U.A., (2008) Eur. Phys. J. C, 55, p. 293Liu, W., Fries, R., (2008) Phys. Rev. C, 77, p. 054902Hwa, R.C., Yang, C.B., (2006) Phys. Rev. Lett., 97, p. 042301Lévai, P., Berényi, D., Pásztor, A., Skokov, V.V., (2011) J. Phys. G, 38, p. 124155Aurenche, P., Zakharov, B.G., (2011) Eur. Phys. J. C, 71, p. 1829Bellwied, R., Markert, C., (2010) Phys. Lett. B, 691, p. 208Xu, Y., (2010) J. Phys. G, 37, p. 094059for the STAR Collaboration (L. Ruan), (2010) J. Phys. G, 37, p. 094013(2011) Phys. Rev. C, 83, p. 024909(2013) Phys. Lett. B, 719, p. 18Barile, F., (2011) AIP Conf. Proc., 1317, p. 71HMPID Technical Design Report CERN/LHCC 98-19 ALICE TDR 1DiMauro, A., (2010) Nucl. Instrum Methods A, 617, p. 424Albrecht, E., (2003) Nucl. Instrum Methods A, 510, p. 262Ando, S., (2006) J. Photopolym. Sci. Technol., 19, p. 351Artuso, M., (2006) Nucl. Instrum Methods A, 558, p. 373Barber, G.J., (2008) Nucl. Instrum Methods A, 593, p. 624Baillon, P., (1989) Nucl. Instrum Methods A, 277, p. 338G. Volpe, Proceedings of the RICH2010 Conference, to be published in Nucl. Instrum Methods ACozza, D., (2003) Nucl. Instrum Methods A, 502, p. 101Santiard, J.-C., (2004) Nucl. Instrum Methods A, 518, p. 498Abbon, P., (2007) Nucl. Instrum Methods A, 577, p. 455Abbon, P., (2008) Nucl. Instrum Methods A, 589, p. 362Hamar, G., Kiss, G., Varga, D., (2011) Nucl. Instrum Methods A, 648, p. 163Varga, D., Kiss, G., Hamar, G., Bencédi, G., (2013) Nucl. Instrum Methods A, 698, p. 11G. Volpe, PhD thesis, Study of Cherenkov detectors for high momentum charged particles identification in the ALICE experiment at LHC, Università degli Studi di Bari, Facolta di Scienze Matematiche, Fisiche e Naturali, Dottorato di ricerca in Fisica XIX ciclo, Anno accademico 2005-2006G. Volpe, PoS HIGH-pTLHC, 022 (2008) The VHMPID detector in the ALICE experiment at LHCD. Cozza, Internal Note RICH-ALICE/98-39(2003) Nucl. Instrum Methods A, 502, p. 300Di Mauro, A., (1999) Nucl. Instrum Methods A, 433, p. 190Hirai, M., Kumano, S., (2010) Prog. Theor. Phys. Suppl., 186, p. 252Albino, S., (2010) Rev. Mod. Phys., 82, p. 2489(2009) Phys. Rev. D, 79, p. 112005Albino B.A. Kniehl, S., Kramer, G., (2010) Phys. Rev. Lett., 104, p. 242001Albino, S., Kniehl, B.A., Kramer, G., (2008) Nucl. Phys. B, 803, p. 42De Florian, D., Sassot, R., Stratman, M., (2007) Phys. Rev. D, 76, p. 074033Albino, S., Kniehl, B.A., Kramer, G., (2008) Nucl. Phys. B, 803, p. 42Hirai, M., Kumano, S., Nagai, T.H., Sudoh, K., (2007) Phys. Rev. D, 75, p. 094009(2009) Eur. Phys. J. C, 62, p. 187Grigoryan, L., (2011) Phys. Rev. C, 83, p. 014904Nagy, Z., Soper, D.E., (2012) JHEP, 6, p. 044Gang, C., Hui-Ling, W., (2011) Int. J. Mod. Phys. E, 20, p. 667Pronko, A., (2005) Int. J. Mod. Phys. A, 20, p. 3723Kaidalov, A.B., (1987) Sov. J. Nucl. Phys., 45, p. 902Kraan, A.C., (2008) AIP Conf. Proc., 1038, p. 45(2007) PoS C, POD07, p. 027(2008) J. Phys. G, 35, p. 104096M. Purschke (for the PHENIX Collaboration), QM 2011 proceedingsH. Appelshaeuser (for the ALICE Collaboration), QM 2011 proceedingsY.J. Lie (for the CMS Collaboration), QM 2011 proceedings(2008) J. Phys. G, 35, p. 044027Wang, X.N., Gyulassy, M., (1991) Phys. Rev. D, 44, p. 3501Gyulassy, M., Lévai, P., Vitev, I., (2000) Phys. Rev. Lett., 85, p. 5535Gyulassy, M., Lévai, P., Vitev, I., (2000) Nucl. Phys. B, 571, p. 197Gyulassy, M., Lévai, P., Vitev, I., (2001) Nucl. Phys. B, 594, p. 371Barnafoldi, G., (2004) Prog. Part. Nucl. Phys., 53, p. 257Jia, J., Lacey, R., (2009) Phys. Rev. C, 79, p. 011901Markert, C., Bellwied, R., Vitev, I., (2008) Phys. Lett. B, 669, p. 92Alver, B., Roland, G., (2010) Phys. Rev. C, 81, p. 054905Gavin, S., McLerran, L., Moschelli, G., (2009) Phys. Rev. C, 79, p. 051902Nagle, J., McCumber, M., (2011) Phys. Rev. C, 83, p. 044908(2004) Eur. Phys. J. C, 33, p. S425G. Paić, A. Ortiz (for the ALICE Collaboration), ALICE-INT-2009-015, PoS(High-pT physics09)007(2011) EPJ Web of Conferences, 13, p. 03004for the ALICE Collaboration (S. Pochybova), (2009) PoS High-pT, physics09, p. 045Ellis, J.R., Geiger, K., Kowalski, H., (1996) Phys. Rev. D, 54, p. 5443(2007) J. Phys. G, 34, p. S685(2000) Eur. Phys. J. C, 17, p. 207(2009) Molnár (for the ALICE Collaboration), Proceedings of the High-$p_T$ Physics for the LHC Workshop, 4-7. , February, PraguearXiv:1008.0413, ALICE-EMCal Physics Performance Report, R. Bellwied(2013) Phys. Lett. B, 718, p. 795(2013) Phys. Lett. B, 719, p. 29for the ALICE Collaboration (Y. Belikov), (2011) J. Phys. G, 38, p. 124078Lin, Z.-W., Ko, C.M., Li, B.-A., Zhang, B., Pal, S., (2005) Phys. Rev. C, 72, p. 064901Pierog, T., Werner, K., (2009) Nucl. Phys. Proc. Suppl., 196, p. 102Mikhailov, K., Werner, K., Karpenko, I., Pierog, T., (2011) Phys. Part. Nucl. Lett., 8, p. 989Appelshauser, H., (2011) J. Phys. G, 38, p. 124014Kraan, A.C., (2008) AIP Conf. Proc., 1038, p. 45Grigoryan, L., (2011) Phys. Rev. C, 83, p. 014904Aurenche, P., Zhakarov, B., (2011) Eur. Phys. J. C, 71, p. 1829arXiv:1208.0448, D. BerenyiKaidalov, A.B., (1987) Yad. Fiz., 45, p. 1452Kaidalov, A.B., (1987) Sov. J. Nucl. Phys., 45, p. 1452Tsallis, C., (2009) Eur. Phys. J. A, 40, p. 257Biro, T.S., (2008) EPL, 84, p. 56003Biro, T.S., Urmossy, K., Schram, Z., (2010) J. Phys. G, 37, p. 094027Biro, T.S., (2013) Physica A, 392, p. 3132Biro, T.S., Barnafoldi, G.G., Van, P., (2013) Eur. Phys. J. A, 49, p. 110(2012) Eur. Phys. J. C, 72, p. 2164(2010) Eur. Phys. J. C, 68, p. 345(2010) Eur. Phys. J. C, 68, p. 89Cleymans, J., Worku, D., (2012) J. Phys. G, 39, p. 025006Cleymans, J., Worku, D., (2012) Eur. Phys. J. A, 48, p. 160Becattini, F., Ferroni, L., (2004) Eur. Phys. J. C, 35, p. 243Becattini, F., Ferroni, L., (2004) Eur. Phys. J. C, 38, p. 225Wilk, G., Wlodarczyk, Z., (2009) Eur. Phys. J. A, 40, p. 299Begun, V.V., Gazdzicki, M., Gorenstein, M.I., (2008) Phys. Rev. C, 78, p. 024904Urmossy, K., Barnaföldi, G.G., Biró, T.S., (2012) Phys. Lett. B, 718, p. 12