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581 results on '"Vaidya, D"'

2. Influence of Vermicomposted Coal Fly Ash on Morphological and Cytological Attributes of Ricinus communis L.

Author

R. U. Raval, D. B. Kapdi, N. H. Bhavsar, V. V. Surati, J. D. Solanki, S. R. Panjabi, P. M. Patel, Y. H. Vaidya, D. N. Verma and K. P. Patel

Subjects
fly ash, pressmud, vermicompost, eisenia foetida, ricinus communis l., Environmental effects of industries and plants, TD194-195, Science (General), Q1-390
Abstract

In view of the environmental problems generated by the large-scale production of fly ash, increasing attention is now being paid to the recycling of fly ash as a good source of nutrients. To reduce the cost of fly ash disposal and best utilization, it aimed to convert the fly ash into valuable vermicompost. Stated throughout the experiment, we opted for a soil sample and fly ash and pressed with different concentrations (control, 20%, 50%, 80% and 100%). Subsequently, all the mixtures were vermicomposted for 60 days by adding 100 Earthworms (Eisenia foetida) in each pile. The X-ray fluorescence spectroscopy measured the composition of the metal in fly ash as well as the nutritional content in the soil. This is followed by examining the morphological characteristics and cytogenetic study of Ricinus communis L. The present study indicated that E. foetida mitigates the toxicity of fly ash and is hence used as valuable vermicompost.

Published
2023
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4. The Dust Content and Radiation Fields of Sample of Galaxies in the ELAIS-N1 Field

Author

Shalima, P., Gogoi, Rupjyoti, Pathak, Amit, Misra, Ranjeev, Gupta, Ranjan, and Vaidya, D. B.

Subjects
Astrophysics - Astrophysics of Galaxies
Abstract

The Mid-IR colors ($F_{8}/F_{24}$) of galaxies together with their IR-UV luminosity correlations can be used to get some insight into the relative abundance of the different dust grain populations present in them. The ELAIS-N1 field contains thousands of galaxies which do not have optical spectra but have been observed in the Mid-IR by {\it Spitzer} and UV by {\it GALEX} making it ideal for these studies. As part of this work we have selected a sample of galaxies from the ELAIS-N1 field which have photometric observations in the MIR and UV as well as photometric redshifts from the SDSS database. We put the constraint that the redshifts are $\le$ 0.1, thereby giving us a total of 309 galaxies. We find that the majority of the galaxies in the sample are PAH dominated due to their high MIR flux ratio. We also find a reasonable correlation between the Mid-IR and the UV luminosities out of which the Mid-IR emission from PAHs at 8 $\mu$m is marginally better correlated than the 24 $\mu$m VSG emission with the UV luminosities. However, if we divide the sample based on their $F_{8}/F_{24}$ ratios which is also an indicator of metallicity, the MIR-UV correlation seems to increase with the $F_{8}/F_{24}$ ratio. But the MIR-UV correlations are not very different for the PAHs and the VSG population within the individual metallicity groups., Comment: 12 pages, accepted for publication in PASP

Published
2015
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6. Association Between Endogenous Sex Hormones and Liver Fat in a Multiethnic Study of Atherosclerosis

Author

Lazo, M, Zeb, I, Nasir, K, Tracy, RP, Budoff, MJ, Ouyang, P, and Vaidya, D

Subjects
Gastroenterology & Hepatology, Clinical Sciences
Abstract

Levels of circulating of sex hormones are associated with glucose metabolism and adiposity, but little is known about their association with ectopic fat. We aimed to characterize the association between circulating sex hormones and liver fat. Methods: We conducted a cross-sectional analysis by using data from the Multiethnic Study of Atherosclerosis to assess the association of the circulating levels of bioavailable testosterone, estradiol, dehydroepiandrosterone, and sex hormone binding globulin (SHBG) with fatty liver. Fatty liver was defined as a reduction of ≤40 Hounsfield units, measured by computed tomography, in 2835 postmenopausal women and 2899 men (45-84 years old; white, black, Hispanic, or Chinese) at 6 centers in the United States. Results: Women in the highest tertile of bioavailable testosterone were significantly more likely to have fatty liver than women in the lowest tertile (odds ratio, 1.77; 95% confidence interval, 1.07-2.92). We found an even greater difference for level of estradiol (odds ratio, 2.49; 95% confidence interval, 1.41-4.39) after adjusting for age, race/ethnicity, waist-to-hip ratio, hypertension, total and high-density lipoprotein cholesterol, smoking, insulin sensitivity, and hormone replacement therapy use. Men in the highest tertile of estradiol level were significantly more likely to have fatty liver than men in the lowest tertile (odds ratio, 2.10; 95% confidence level, 1.29-3.40). Men in the highest tertile of SHBG were less likely to have fatty liver than those in the lowest tertile (odds ratio, 0.46; 95% confidence interval, 0.27-0.77). Other associations between hormone levels and fatty liver were not statistically significant. Conclusions: On the basis of a cross-sectional study, postmenopausal women with high levels of bioavailable testosterone are at greater risk for fatty liver. In men, higher levels of SHBG are associated with reduced risk for fatty liver. Higher levels of estradiol are associated with fatty liver in both sexes. This pattern is consistent with the sex-specific associations of sex hormones with other cardiometabolic risk factors.

Published
2015

7. Interstellar Dust models towards some IUE stars

Author

Katyal, Nisha, Gupta, Ranjan, and Vaidya, D B

Subjects
Astrophysics - Solar and Stellar Astrophysics, Astrophysics - Astrophysics of Galaxies
Abstract

We study the extinction properties of the composite dust grains, consisting of host silicate spheroids and graphite as inclusions, using discrete dipole approximation (DDA). We calculate the extinction cross sections of the composite grains in the ultraviolet spectral region, 1200\AA -3200\AA and study the variation in extinction as a function of the volume fraction of the inclusions. We compare the model extinction curves with the observed interstellar extinction curves obtained from the data given by the International Ultraviolet Explorer (IUE) satellite. Our results for the composite grains show a distinct variation in the extinction efficiencies with the variation in the volume fraction of the inclusions. In particular, it is found that the wavelength of peak absorption at `2175\AA' shifts towards the longer wavelength with the variation in the volume fraction of inclusions. We find that the composite grain models with the axial ratios viz. 1.33 and 2.0 fit the observed extinction reasonably well with a grain size distribution, a = 0.005-0.250$\mu m$. Moreover, our results of the composite grains clearly indicate that the inhomogeneity in the grain structure, composition and the surrounding media modifies the extinction properties of the grains., Comment: 11 pages, 8 figures, accepted for publication in PASP

Published
2013
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8. Interstellar Grains: Effect of Inclusions on Extinction

Author

Katyal, Nisha, Gupta, Ranjan, and Vaidya, D. B.

Subjects
Astrophysics - Solar and Stellar Astrophysics
Abstract

A composite dust grain model which simultaneously explains the observed interstellar extinction, polarization, IR emission and the abundance constraints, is required. We present a composite grain model, which is made up of a host silicate oblate spheroid and graphite inclusions. The interstellar extinction curve is evaluated in the spectral region 3.4-0.1$\mu m$ using the extinction efficiencies of the composite spheroidal grains for three axial ratios. Extinction curves are computed using the discrete dipole approximation (DDA). The model curves are subsequently compared with the average observed interstellar extinction curve and with an extinction curve derived from the IUE catalogue data., Comment: 10 pages, 3 figures

Published
2011
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9. Infrared Emission from the Composite Grains: Effects of Inclusions and Porosities on the 10 and 18 $\mu m$ Features

Author

Vaidya, D. B. and Gupta, Ranjan

Subjects
Astrophysics - Solar and Stellar Astrophysics
Abstract

In this paper we study the effects of inclusions and porosities on the emission properties of silicate grains and compare the model curves with the observed infrared emission from circumstellar dust. We calculate the absorption efficiency of the composite grain, made up of a host silicate oblate spheroid and inclusions of ice/graphite/or voids, in the spectral region 5.0-25.0$\mu m$. The absorption efficiencies of the composite spheroidal oblate grains for three axial ratios are computed using the discrete dipole approximation (DDA). We study the absorption as a function of the volume fraction of the inclusions and porosity. In particular, we study the variation in the $10\mu m$ and $18\mu m$ emission features with the volume fraction of the inclusions and porosities. We then calculate the infrared fluxes for these composite grains at several dust temperatures (T=200-350K) and compare the model curves with the average observed IRAS-LRS curve, obtained for circumstellar dust shells around oxygen rich M-type stars. The model curves are also compared with two other individual stars. The results on the composite grains clearly indicate that the silicate feature at 10$\mu m$ shifts with the volume fraction of graphite inclusions. The feature does not shift with the porosity. Both the features do not show any broadening with the inclusions or porosity. The absorption efficiencies of the composite grains calculated using DDA and Effective Medium Approximation (EMA) do not agree. The composite grain models presented in this study need to be compared with the observed IR emission from the circumstellar dust around a few more stars., Comment: 12 pages, 12 figures, 7 tables; To appear in A & A, 2011

Published
2011
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10. Composite Interstellar Grains

Author

Vaidya, D. B., Gupta, Ranjan, and Snow, T. P.

Subjects
Astrophysics
Abstract

The composite grain is made up of a host silicate spheroid and graphite inclusions. The extinction efficiencies of the composite spheroidal grains for three axial ratios are computed using the discrete dipole approximation (DDA). The interstellar extinction curve is evaluated in the spectral region 3.40--0.10$\mu m$ using the extinction efficiencies of the composite spheroidal grains. The model extinction curves are then compared with the average observed interstellar extinction curve. We also calculate the linear polarization for the spheroidal composite grains at three orientation angles and find the wavelength of maximum polarization. Further, we estimate the volume extinction factor, an important parameter from the point of view of cosmic abundance, for the composite grain models that reproduce the average observed interstellar extinction. The estimated abundances derived from the composite grain models for both carbon and silicon are found to be lower than that are predicted by the bare silicate/graphite grain models but these values are still higher than that are implied from the recent ISM values., Comment: 11 pages, 12 figures, 5 tables To appear in 2007 MNRAS

Published
2007
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11. Interstellar Extinction by Spheroidal Dust Grains

Author

Gupta, Ranjan, Mukai, Tadashi, Vaidya, D. B., Sen, Asoke K., and Okada, Yasuhiko

Subjects
Astrophysics
Abstract

Observations of interstellar extinction and polarization indicate that the interstellar medium consists of aligned non-spherical dust grains which show variation in the interstellar extinction curve for wavelengths ranging from NIR to UV. To model the extinction and polarization, one cannot use the Mie theory which assumes the grains as solid spheres. We have used a T-matrix based method for computing the extinction efficiencies of spheroidal silicate and graphite grains of different shapes (axial ratios) and sizes and used these efficiencies to evaluate the interstellar extinction curve in the wavelength range 3.4--1.0 microns. A best fit linear combination of silicate and graphite grains of not very large axial ratio, fits the observed extinction curve reasonably well. We calculate the volume extinction factor Vc, which is an important parameter from the point of view of the cosmic abundance, for the spheroidal grain models that reproduce the interstellar extinction curve. We find that the shape of the grains do not affect the volume extinction factor. Finally we have also studied the extinction and linear polarization efficiencies for aligned spheroids. The results show that the shape of grains affects the linear polarization efficiencies considerably for various orientation angles of the spheroids., Comment: 10 pages, 6 figure To appear in A & A, 2005

Published
2005
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12. Scattering properties and composition of cometary dust

Author

Gupta, Ranjan, Vaidya, D. B., Dobbie, J. S., and Chylek, P.

Subjects
Astrophysics
Abstract

Composition of Comet dust obtained by the dust impact analyser on the Halley probes indicated that the comet dust is a mixure of silicate and carbonaceous material. The collected interplanetary dust particles (IDP's) are fluffy and composite having grains of several different types stuck together. Using Discrete Dipole Approximation (DDA) we study the scattering properties of composite grains. In particular, we study the angular distribution of the scattered intensity and linear polarization of composite grains. We assume that the composite grains are made up of host silicate sphere/spheroid with the inclusions of graphite. Results of our calculations on the composite grains show that the angle of maximum polarization shifts, and the degree of polarizaion varies with the volume fraction of inclusions. We use these results on the composite grains to interpret the observed scattering in the cometary dust., Comment: 22 pages, 11 figures. To appear in Astrophysics & Space Science, 2005

Published
2005
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13. A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple loci implicated in sex steroid hormone regulation

Author

Cummings, Steven, Coviello, AD, Haring, R, Wellons, M, Vaidya, D, Lehtimäki, T, Keildson, S, Lunetta, KL, He, C, Fornage, M, and Lagou, V

Abstract

Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and

Published
2012

15. Prognostic value of a left atrioventricular coupling index (LACI) in pre- and post-menopausal women. from the multi-ethnic study of atherosclerosis (MESA)

Author

Pezel, T, primary, Michos, E D, additional, Varadarajan, V, additional, Shabani, M, additional, Ambale Venkatesh, B, additional, Vaidya, D, additional, Kato, Y, additional, De Vasconcellos, H, additional, Heckbert, S, additional, Wu, C, additional, Post, W, additional, Bluemke, D, additional, Allison, M A, additional, and Lima, J, additional

Published
2022
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16. AS3MT, Locus 10q24 and arsenic metabolism biomarkers in American Indians: The Strong Heart Family Study

Author

Balakrishnan, P, primary, Vaidya, D, additional, Franceschini, N, additional, Voruganti, V, additional, Gribble, M, additional, Haack, K, additional, Laston, S, additional, Umans, J, additional, Francesconi, K, additional, Goessler, W, additional, North, K, additional, Lee, E, additional, Yracheta, J, additional, Best, L, additional, MacCluer, J, additional, Kent, J, additional, Cole, S, additional, and Navas-Acien, A, additional

Published
2016
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17. Obesity Partially Mediates the Diabetogenic Effect of Lowering LDL Cholesterol

Author

Universitat Rovira i Virgili, Wu P; Moon JY; Daghlas I; Franco G; Porneala BC; Ahmadizar F; Richardson TG; Isaksen JL; Hindy G; Yao J; Sitlani CM; Raffield LM; Yanek LR; Feitosa MF; Cuadrat RRC; Qi Q; Ikram MA; Ellervik C; Ericson U; Goodarzi MO; Brody JA; Lange L; Mercader JM; Vaidya D; An P; Schulze MB; Masana L; Ghanbari M; Olesen MS; Cai J; Guo X; Floyd JS; Jager S; Province MA; Kalyani RR; Psaty BM; Orho-Melander M; Ridker PM; Kanters JK; Uitterlinden A; Smith GD; Gill D; Kaplan RC; Kavousi M; Raghavan S; Chasman DI; Rotter JI; Meigs JB; Florez JC; Dupuis J; Liu CT; Merino J, Universitat Rovira i Virgili, and Wu P; Moon JY; Daghlas I; Franco G; Porneala BC; Ahmadizar F; Richardson TG; Isaksen JL; Hindy G; Yao J; Sitlani CM; Raffield LM; Yanek LR; Feitosa MF; Cuadrat RRC; Qi Q; Ikram MA; Ellervik C; Ericson U; Goodarzi MO; Brody JA; Lange L; Mercader JM; Vaidya D; An P; Schulze MB; Masana L; Ghanbari M; Olesen MS; Cai J; Guo X; Floyd JS; Jager S; Province MA; Kalyani RR; Psaty BM; Orho-Melander M; Ridker PM; Kanters JK; Uitterlinden A; Smith GD; Gill D; Kaplan RC; Kavousi M; Raghavan S; Chasman DI; Rotter JI; Meigs JB; Florez JC; Dupuis J; Liu CT; Merino J

Abstract

OBJECTIVE LDL cholesterol (LDLc)-lowering drugs modestly increase body weight and type 2 diabetes risk, but the extent to which the diabetogenic effect of lowering LDLc is mediated through increased BMI is unknown. RESEARCH DESIGN AND METHODS We conducted summary-level univariable and multivariable Mendelian randomization (MR) analyses in 921,908 participants to investigate the effect of lowering LDLc on type 2 diabetes risk and the proportion of this effect mediated through BMI. We used data from 92,532 participants from 14 observational studies to replicate findings in individual-level MR analyses. RESULTS A 1-SD decrease in genetically predicted LDLc was associated with increased type 2 diabetes odds (odds ratio [OR] 1.12 [95% CI 1.01, 1.24]) and BMI (b 5 0.07 SD units [95% CI 0.02, 0.12]) in univariable MR analyses. The multivariable MR analysis showed evidence of an indirect effect of lowering LDLc on type 2 diabetes through BMI (OR 1.04 [95% CI 1.01, 1.08]) with a proportion mediated of 38% of the total effect (P 5 0.03). Total and indirect effect estimates were similar across a number of sensitivity analyses. Individual-level MR analyses confirmed the indirect effect of lowering LDLc on type 2 diabetes through BMI with an estimated proportion mediated of 8% (P 5 0.04). CONCLUSIONS These findings suggest that the diabetogenic effect attributed to lowering LDLc is partially mediated through increased BMI. Our results could help advance understanding of adipose tissue and lipids in type 2 diabetes pathophysiology and inform strategies to reduce diabetes risk among individuals taking LDLc-lowering medications.

Published
2022

18. Prognostic value of left atrioventricular coupling index (LACI) in pre- and post-menopausal women : from the multi-ethnic study of atherosclerosis (MESA)

Author

Pezel, T, primary, Michos, E, additional, Varadarajan, V, additional, Shabani, M, additional, Ambale Venkatesh, B, additional, Vaidya, D, additional, Kato, Y, additional, De Vasconcellos, H, additional, Heckbert, S, additional, Wu, C, additional, Post, WENDY, additional, Bluemke, D, additional, Allison, M, additional, and Lima, J, additional

Published
2022
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21. Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices

Author

Natarajan, P. (Pradeep), Pampana, A. (Akhil), Graham, S. E. (Sarah E.), Ruotsalainen, S. E. (Sanni E.), Perry, J. A. (James A.), de Vries, P. S. (Paul S.), Broome, J. G. (Jai G.), Pirruccello, J. P. (James P.), Honigbere, M. C. (Michael C.), Aragam, K. (Krishna), Wolford, B. (Brooke), Brody, J. A. (Jennifer A.), Antonacci-Fulton, L. (Lucinda), Arden, M. (Moscati), Aslibekyan, S. (Stella), Assimes, T. L. (Themistocles L.), Ballantyne, C. M. (Christie M.), Bielak, L. F. (Lawrence F.), Bisl, J. C. (Joshua C.), Cade, B. E. (Brian E.), Do, R. (Ron), Doddapaneni, H. (Harsha), Emery, L. S. (Leslie S.), Hung, Y.-J. (Yi-Jen), Irvin, M. R. (Marguerite R.), Khan, A. T. (Alyna T.), Lange, L. (Leslie), Lee, J. (Jiwon), Lemaitre, R. N. (Rozenn N.), Martin, L. W. (Lisa W.), Metcalf, G. (Ginger), Montasser, M. E. (May E.), Moon, J.-Y. (Jee-Young), Muzny, D. (Donna), Connell, J. R. (Jeffrey R. O.), Palmer, N. D. (Nicholette D.), Peralta, J. M. (Juan M.), Peyser, P. A. (Patricia A.), Stilp, A. M. (Adrienne M.), Tsai, M. (Michael), Wang, F. F. (Fei Fei), Weeks, D. E. (Daniel E.), Yanek, L. R. (Lisa R.), Wilson, J. G. (James G.), Abecasis, G. (Goncalo), Arnett, D. K. (Donna K.), Becker, L. C. (Lewis C.), Blangercy, J. (John), Boerwinkle, E. (Eric), Bowden, D. W. (Donald W.), Chang, Y.-C. (Yi-Cheng), Chen, Y. I. (Yii-Der, I), Choi, W. J. (Won Jung), Correa, A. (Adolfo), Curran, J. E. (Joanne E.), Daly, M. J. (Mark J.), DutcherE, S. K. (Susan K.), Ellinor, P. T. (Patrick T.), Fornage, M. (Myriam), Freedman, B. I. (Barry, I), Gabriel, S. (Stacey), Germer, S. (Soren), Gibbs, R. A. (Richard A.), He, J. (Jiang), Hveem, K. (Kristian), Jarvik, G. P. (Gail P.), Kaplan, R. C. (Robert C.), Kardia, S. L. (Sharon L. R.), Kennyn, E. (Eimear), Kim, R. W. (Ryan W.), Kooperberg, C. (Charles), Laurie, C. C. (Cathy C.), Lee, S. (Seonwook), Lloyd-Jones, D. M. (Don M.), Loos, R. J. (Ruth J. F.), Lubitz, S. A. (Steven A.), Mathias, R. A. (Rasika A.), Martinez, K. A. (Karine A. Viaud), McGarvey, S. T. (Stephen T.), Mitche, B. D. (Braxton D.), Nickerson, D. A. (Deborah A.), North, K. E. (Kari E.), Palotie, A. (Aarno), Park, C. J. (Cheol Joo), Psat, B. M. (Bruce M. Y.), Rao, D. C. (D. C.), Redline, S. (Susan), Reiner, A. P. (Alexander P.), Seo, D. (Daekwan), Seo, J.-S. (Jeong-Sun), Smith, A. V. (Albert, V), Tracy, R. P. (Russell P.), Kathiresan, S. (Sekar), Cupples, L. A. (L. Adrienne), Rotten, J. I. (Jerome, I), Morrison, A. C. (Alanna C.), Rich, S. S. (Stephen S.), Ripatti, S. (Samuli), Wilier, C. (Cristen), Peloso, G. M. (Gina M.), Vasan, R. S. (Ramachandran S.), Abe, N. (Namiko), Albert, C. (Christine), Almasy, L. (Laura), Alonso, A. (Alvaro), Ament, S. (Seth), Anderson, P. (Peter), Applebaum-Bowden, D. (Deborah), Arking, D. (Dan), Ashley-Koch, A. (Allison), Auer, P. (Paul), Avramopoulos, D. (Dimitrios), Barnard, J. (John), Barnes, K. (Kathleen), Barr, R. G. (R. Graham), Barron-Casella, E. (Emily), Beaty, T. (Terri), Becker, D. (Diane), Beer, R. (Rebecca), Begum, F. (Ferdouse), Beitelshees, A. (Amber), Benjamin, E. (Emelia), Bezerra, M. (Marcos), Bielak, L. (Larry), Blackwel, T. (Thomas), Bowler, R. (Russell), Broecke, U. (Ulrich), Bunting, K. (Karen), Burchard, E. (Esteban), Buth, E. (Erin), Cardwel, J. (Jonathan), Carty, C. (Cara), Casaburi, R. (Richard), Casella, J. (James), Chaffin, M. (Mark), Chang, C. (Christy), Chasman, D. (Daniel), Chavan, S. (Sameer), Chen, B.-J. (Bo-Juen), Chen, W.-M. (Wei-Min), Chol, M. (Michael), Choi, S. H. (Seung Hoan), Chuang, L.-M. (Lee-Ming), Chung, M. (Mina), Conomos, M. P. (Matthew P.), Cornell, E. (Elaine), Crapo, J. (James), Curtis, J. (Jeffrey), Custer, B. (Brian), Damcott, C. (Coleen), Darbar, D. (Dawood), Das, S. (Sayantan), David, S. (Sean), Davis, C. (Colleen), Daya, M. (Michelle), de Andrade, M. (Mariza), DeBaunuo, M. (Michael), Duan, Q. (Qing), Devine, R. D. (Ranjan Deka Dawn DeMeo Scott), Duggirala, Q. R. (Qing Ravi), Durda, J. P. (Jon Peter), Dutcher, S. (Susan), Eaton, C. (Charles), Ekunwe, L. (Lynette), Farber, C. (Charles), Farnaml, L. (Leanna), Fingerlin, T. (Tasha), Flickinger, M. (Matthew), Franceschini, N. (Nora), Fu, M. (Mao), Fullerton, S. M. (Stephanie M.), Fulton, L. (Lucinda), Gan, W. (Weiniu), Gao, Y. (Yan), Gass, M. (Margery), Ge, B. (Bruce), Geng, X. P. (Xiaoqi Priscilla), Gignoux, C. (Chris), Gladwin, M. (Mark), Glahn, D. (David), Gogarten, S. (Stephanie), Gong, D.-W. (Da-Wei), Goring, H. (Harald), Gu, C. C. (C. Charles), Guan, Y. (Yue), Guo, X. (Xiuqing), Haessler, J. (Jeff), Hall, M. (Michael), Harris, D. (Daniel), Hawle, N. Y. (Nicola Y.), Heavner, B. (Ben), Heckbert, S. (Susan), Hernandez, R. (Ryan), Herrington, D. (David), Hersh, C. (Craig), Hidalgo, B. (Bertha), Hixson, J. (James), Hokanson, J. (John), Hong, E. (Elliott), Hoth, K. (Karin), Hsiung, C. A. (Chao Agnes), Huston, H. (Haley), Hwu, C. M. (Chii Min), Jackson, R. (Rebecca), Jain, D. (Deepti), Jaquish, C. (Cashell), Jhun, M. A. (Min A.), Johnsen, J. (Jill), Johnson, A. (Andrew), Johnson, C. (Craig), Johnston, R. (Rich), Jones, K. (Kimberly), Kang, H. M. (Hyun Min), Kaufman, L. (Laura), Kell, S. Y. (Shannon Y.), Kessler, M. (Michael), Kinney, G. (Greg), Konkle, B. (Barbara), Kramer, H. (Holly), Krauter, S. (Stephanie), Lange, C. (Christoph), Lange, E. (Ethan), Laurie, C. (Cecelia), LeBoff, M. (Meryl), Lee, S. S. (Seunggeun Shawn), Lee, W.-J. (Wen-Jane), LeFaive, J. (Jonathon), Levine, D. (David), Levy, D. (Dan), Lewis, J. (Joshua), Li, Y. (Yun), Lin, H. (Honghuang), Lin, K. H. (Keng Han), Lin, X. (Xihong), Liu, S. (Simin), Liu, Y. (Yongmei), Lunetta, K. (Kathryn), Luo, J. (James), Mahaney, M. (Michael), Make, B. (Barry), Manichaikul, A. (Ani), Mansonl, J. (JoAnn), Margolin, L. (Lauren), Mathai, S. (Susan), McArdle, P. (Patrick), Mcdonald, M.-L. (Merry-Lynn), McFarland, S. (Sean), McHugh, C. (Caitlin), Mei, H. (Hao), Meyers, D. A. (Deborah A.), Mikulla, J. (Julie), Min, N. (Nancy), Minear, M. (Mollie), Minster, R. L. (Ryan L.), Musani, S. (Solomon), Mwasongwe, S. (Stanford), Mychaleckyj, J. C. (Josyf C.), Nadkarni, G. (Girish), Naik, R. (Rakhi), Naseri, T. (Take), Nekhai, S. (Sergei), Nelson, S. C. (Sarah C.), Nickerson, D. (Deborah), Connell, J. O. (Jeff O.), Connor, T. O. (Tim O.), Ochs-Balcom, H. (Heather), Pankow, J. (James), Papanicolaou, G. (George), Parkerl, M. (Margaret), Parsa, A. (Afshin), Penchey, S. (Sara), Perez, M. (Marco), Peters, U. (Ulrike), Phillips, L. S. (Lawrence S.), Phillips, S. (Sam), Pollin, T. (Toni), Post, W. (Wendy), Becker, J. P. (Julia Powers), Boorgula, M. P. (Meher Preethi), Preuss, M. (Michael), Prokopenko, D. (Dmitry), Qasba, P. (Pankaj), Qiao, D. (Dandi), Rafaels, N. (Nicholas), Raffield, L. (Laura), Rasmussen-Torvik, L. (Laura), Ratan, A. (Aakrosh), Reed, R. (Robert), Reganl, E. (Elizabeth), Reupena, M. S. (Muagututi Sefuiva), Rice, K. (Ken), Roden, D. (Dan), Roselli, C. (Carolina), Ruczinski, I. (Ingo), Russel, P. (Pamela), Ruuska, S. (Sarah), Ryan, K. (Kathleen), Sabino, E. C. (Ester Cerdeira), Sakornsakolpatl, P. (Phuwanat), Salzberg, S. (Steven), Sandow, K. (Kevin), Sankaran, V. G. (Vijay G.), Scheller, C. (Christopher), Schmidt, E. (Ellen), Schwander, K. (Karen), Schwartz, D. (David), Sciurba, F. (Frank), Seidman, C. (Christine), Seidman, J. (Jonathan), Sheehan, V. (Vivien), Shetty, A. (Amol), Shetty, A. (Aniket), Sheu, W. H. (Wayne Hui-Heng), Shoemaker, M. B. (M. Benjamin), Silver, B. (Brian), Silvermanl, E. (Edwin), Smith, J. (Jennifer), Smith, J. (Josh), Smith, N. (Nicholas), Smith, T. (Tanja), Smoller, S. (Sylvia), Snively, B. (Beverly), Soferlm, T. (Tamar), Streeten, E. (Elizabeth), Su, J. L. (Jessica Lasky), Sung, Y. J. (Yun Ju), Sylvia, J. (Jody), Sztalryd, C. (Carole), Taliun, D. (Daniel), Tang, H. (Hua), Taub, M. (Margaret), Taylor, K. D. (Kent D.), Taylor, S. (Simeon), Telen, M. (Marilyn), Thornton, T. A. (Timothy A.), Tinker, L. (Lesley), Tirschwel, D. (David), Tiwari, H. (Hemant), Vaidya, D. (Dhananjay), VandeHaar, P. (Peter), Vrieze, S. (Scott), Walker, T. (Tarik), Wallace, R. (Robert), Waits, A. (Avram), Wan, E. (Emily), Wang, H. (Heming), Watson, K. (Karol), Weir, B. (Bruce), Weiss, S. (Scott), Weng, L.-C. (Lu-Chen), Williams, K. (Kayleen), Williams, L. K. (L. Keoki), Wilson, C. (Carla), Wong, Q. (Quenna), Xu, H. (Huichun), Yang, I. (Ivana), Yang, R. (Rongze), Zaghlou, N. (Norann), Zekavat, M. (Maryam), Zhang, Y. (Yingze), Zhao, S. X. (Snow Xueyan), Zhao, W. (Wei), Zni, D. (Degui), Zhou, X. (Xiang), Zhu, X. (Xiaofeng), Zody, M. (Michael), Zoellner, S. (Sebastian), Daly, M. (Mark), Jacob, H. (Howard), Matakidou, A. (Athena), Runz, H. (Heiko), John, S. (Sally), Plenge, R. (Robert), McCarthy, M. (Mark), Hunkapiller, J. (Julie), Ehm, M. (Meg), Waterworth, D. (Dawn), Fox, C. (Caroline), Malarstig, A. (Anders), Klinger, K. (Kathy), Call, K. (Kathy), Mkel, T. (Tomi), Kaprio, J. (Jaakko), Virolainen, P. (Petri), Pulkki, K. (Kari), Kilpi, T. (Terhi), Perola, M. (Markus), Partanen, J. (Jukka), Pitkranta, A. (Anne), Kaarteenaho, R. (Riitta), Vainio, S. (Seppo), Savinainen, K. (Kimmo), Kosma, V.-M. (Veli-Matti), Kujala, U. (Urho), Tuovila, O. (Outi), Hendolin, M. (Minna), Pakkanen, R. (Raimo), Waring, J. (Jeff), Riley-Gillis, B. (Bridget), Liu, J. (Jimmy), Biswas, S. (Shameek), Diogo, D. (Dorothee), Marshall, C. (Catherine), Hu, X. (Xinli), Gossel, M. (Matthias), Schleutker, J. (Johanna), Arvas, M. (Mikko), Hinttala, R. (Reetta), Kettunen, J. (Johannes), Laaksonen, R. (Reijo), Mannermaa, A. (Arto), Paloneva, J. (Juha), Soininen, H. (Hilkka), Julkunen, V. (Valtteri), Remes, A. (Anne), Klviinen, R. (Reetta), Hiltunen, M. (Mikko), Peltola, J. (Jukka), Tienari, P. (Pentti), Rinne, J. (Juha), Ziemann, A. (Adam), Waring, J. (Jeffrey), Esmaeeli, S. (Sahar), Smaoui, N. (Nizar), Lehtonen, A. (Anne), Eaton, S. (Susan), Landenper, S. (Sanni), Michon, J. (John), Kerchner, G. (Geoff), Bowers, N. (Natalie), Teng, E. (Edmond), Eicher, J. (John), Mehta, V. (Vinay), Gormle, P. Y. (Padhraig Y.), Linden, K. (Kari), Whelan, C. (Christopher), Xu, F. (Fanli), Pulford, D. (David), Frkkil, M. (Martti), Pikkarainen, S. (Sampsa), Jussila, A. (Airi), Blomster, T. (Timo), Kiviniemi, M. (Mikko), Voutilainen, M. (Markku), Georgantas, B. (Bob), Heap, G. (Graham), Rahimov, F. (Fedik), Usiskin, K. (Keith), Maranville, J. (Joseph), Lu, T. (Tim), Oh, D. (Danny), Kalpala, K. (Kirsi), Miller, M. (Melissa), McCarthy, L. (Linda), Eklund, K. (Kari), Palomki, A. (Antti), Isomki, P. (Pia), Piri, L. (Laura), Kaipiainen-Seppnen, O. (Oili), Lertratanaku, A. (Apinya), Bing, D. C. (David Close Marla Hochfeld Nan), Gordillo, J. E. (Jorge Esparza), Mars, N. (Nina), Laitinen, T. (Tarja), Pelkonen, M. (Margit), Kauppi, P. (Paula), Kankaanranta, H. (Hannu), Harju, T. (Terttu), Greenberg, S. (Steven), Chen, H. (Hubert), Betts, J. (Jo), Ghosh, S. (Soumitra), Salomaa, V. (Veikko), Niiranen, T. (Teemu), Juonala, M. (Markus), Metsrinne, K. (Kaj), Khnen, M. (Mika), Junttila, J. (Juhani), Laakso, M. (Markku), Pihlajamki, J. (Jussi), Sinisalo, J. (Juha), Taskinen, M.-R. (Marja-Riitta), Tuomi, T. (Tiinamaija), Laukkanen, J. (Jari), Challis, B. (Ben), Peterson, A. (Andrew), Chu, A. (Audrey), Parkkinen, J. (Jaakko), Muslin, A. (Anthony), Joensuu, H. (Heikki), Meretoja, T. (Tuomo), Aaltonen, L. (Lauri), Auranen, A. (Annika), Karihtala, P. (Peeter), Kauppila, S. (Saila), Auvinen, P. (Pivi), Elenius, K. (Klaus), Popovic, R. (Relja), Schutzman, J. (Jennifer), Loboda, A. (Andrey), Chhibber, A. (Aparna), Lehtonen, H. (Heli), McDonough, S. (Stefan), Crohns, M. (Marika), Kulkarni, D. (Diptee), Kaarniranta, K. (Kai), Turunen, J. (Joni), Ollila, T. (Terhi), Seitsonen, S. (Sanna), Uusitalo, H. (Hannu), Aaltonen, V. (Vesa), Uusitalo-Jrvinen, H. (Hannele), Luodonp, M. (Marja), Hautala, N. (Nina), Strauss, E. (Erich), Chen, H. (Hao), Podgornaia, A. (Anna), Hoffman, J. (Joshua), Tasanen, K. (Kaisa), Huilaja, L. (Laura), Hannula-Jouppi, K. (Katariina), Salmi, T. (Teea), Peltonen, S. (Sirkku), Koulu, L. (Leena), Harvima, I. (Ilkka), Wu, Y. (Ying), Choy, D. (David), Jalanko, A. (Anu), Kajanne, R. (Risto), Lyhs, U. (Ulrike), Kaunisto, M. (Mari), Davis, J. W. (Justin Wade), Quarless, D. (Danjuma), Petrovski, S. (Slav), Chen, C.-Y. (Chia-Yen), Bronson, P. (Paola), Yang, R. (Robert), Chang, D. (Diana), Bhangale, T. (Tushar), Holzinger, E. (Emily), Wang, X. (Xulong), Chen, X. (Xing), Auro, K. (Kirsi), Wang, C. (Clarence), Xu, E. (Ethan), Auge, F. (Franck), Chatelain, C. (Clement), Kurki, M. (Mitja), Karjalainen, J. (Juha), Havulinna, A. (Aki), Palin, K. (Kimmo), Palta, P. (Priit), Parolo, P. D. (Pietro Della Briotta), Zhou, W. (Wei), Lemmel, S. (Susanna), Rivas, M. (Manuel), Harju, J. (Jarmo), Lehisto, A. (Arto), Ganna, A. (Andrea), Llorens, V. (Vincent), Karlsson, A. (Antti), Kristiansson, K. (Kati), Hyvrinen, K. (Kati), Ritari, J. (Jarmo), Wahlfors, T. (Tiina), Koskinen, M. (Miika), Pylkäs, K. (Katri), Kalaoja, M. (Marita), Karjalainen, M. (Minna), Mantere, T. (Tuomo), Kangasniemi, E. (Eeva), Heikkinen, S. (Sami), Laakkonen, E. (Eija), Kononen, J. (Juha), Loukola, A. (Anu), Laiho, P. (Pivi), Sistonen, T. (Tuuli), Kaiharju, E. (Essi), Laukkanen, M. (Markku), Jrvensivu, E. (Elina), Lhteenmki, S. (Sini), Mnnikk, L. (Lotta), Wong, R. (Regis), Mattsson, H. (Hannele), Hiekkalinna, T. (Tero), Jimnez, M. G. (Manuel Gonzlez), Donner, K. (Kati), Prn, K. (KaIle), Nunez-Fontarnau, J. (Javier), Kilpelinen, E. (Elina), Sipi, T. P. (Timo P.), Brein, G. (Georg), Dada, A. (Alexander), Awaisa, G. (Ghazal), Shcherban, A. (Anastasia), Sipil, T. (Tuomas), Laivuori, H. (Hannele), Kiiskinen, T. (Tuomo), Siirtola, H. (Harri), Tabuenca, J. G. (Javier Gracia), Kallio, L. (Lila), Soini, S. (Sirpa), Pitknen, K. (Kimmo), and Kuopio, T. (Teijo)

Subjects
Cardiovascular genetics, Genome-wide association studies
Abstract

Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10−72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10−4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10−5). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids.

Published
2021

29. Abstracts

Author

Lacombe, P., Blaise, G., Plante, F., Hollmann, C., Penning, D. H., Patrick, J., Brien, J., Orser, B., Bertlik, M., Fedorko, L., O’Brodovich, H., Santos, A. C., Pedersen, H., Morishima, H. O., Finster, M., Arthur, G. R., Covino, B. G., Perreault, C., Albert, J. F., Couture, P., Meloche, R., Elliott, R. D., Stockwell, M., Roy, W. L., Lerman, J., McIntyre, B. G., Yee, D. A., Hunziker, P., Koch, J. P., Devitt, J. H., Daley, M. D., Colmenares, M. E., Norman, P. H., Sandler, A. N., Oyston, J. P., Knill, R. L., Skinner, M. I., Novick, T., Vandenberghe, H. M., Moote, C. A., Donati, François, Meistelman, Claude, Plaud, Benoit, Guay, J., Reinberg, C., Rivard, G. E., Poitras, B., Mathews, S., David, M., Dawe, G., Hall, R. I., Stringer D. G., Sandler A. N., Panos L., Lawson S., Einarson T. R., Badner N., Fiset, P., Balendran, P., Donati, F., Bevan, D. R., Hung, O. R., Varvel, J., Shafer, S., Stanski, D. R., Crawford, M. W., Carmichael, F. J., Orrego, H., Saldivia, V., Lerman, J., Ralley, F. E., Murkin, J. M., Hudson, R. J., Dunn, G., Perreault, L., Hardy, J. F., Donelly, M., Scott, W. A. C., Daly, D. S., McAllister, J. D., Sharpe, M. D., Manninen, P. H., Cuillerier, D. J., Gelb, A. W., Nantau, W. E., Leon, J. E., Bissonnette, B., Davies, K. R., Gelb, A., Boughner, D. R., Bisnaire, D., Shokeir, O., Code, W. E., Hertz, L., White, H. S., Hong, M., Milne, B., Loomis, C., Jhamandas, K., Lam A. M., Slee T., Hirst R., Cooper J. O., Pavlin E. G., Sundling N., Mutch, W. A. C., Ringaert, K., Ewart, F., White, I., Donen, N., Winn H. R., Grady M. S., Murkin, J. M., Farrar, J. K., McNeill, B., Lok, P., Nalder, B., Jivraj, K., Golar, S., Ford, G., Rosenal, T., Puchalski, S. A., Morison, D. H., Collins, R. M., Gascoyne, R. D., Taylor, R. H., Lerman, J., Gauthier R. A., Chung F., Dyck B., Romanelli J. R., Chapman K. R., Lavoie, J., Marcin, R., Tétrault, J. P., Murphy, I. L., Splinter, W. M., Segstro, R., Morley-Forster, P. K., Lu, G., Lessard, M. R., Trépanier, C. A., Brochu, J. G., Coté, J. J., Denault, P. H., Baribault, J. P., Gordon, A. R., O’Connor, J. P., Ramsay, J. G., Malcolm, I., Chang, P. C., Reynolds, F. B., Lang, S. A., Ha, H. C., Grant, R. P., Dolman, J. F., Harper, J. A., White, S. A., Parsons, D. G., Evans, K. G., Merrick, P., Trivedi, Narendra S., Halpern, Meyer, Robalino, Joffre, Shevde, Ketan, Wang, B. C., Hiller, J. M., Simon, E. J., Hillman, D. E., Li, D., Rosenberg, C., Turndorf, H., Penning, J. P., Nagasaka, Hiroshi, Yaksh, T. L., Forrest, J. B., Lam, L., Woo, J., Rifkind, A., Broadman, L., Hannallah, R., DeLeon, E., Reff, R., Tanaka, K., Watanabe, R., Harada, T., Dan, K., Aull, L., Woodward, E. R., Rout, R. W., Paulus, D. A., Reimer, E. J., Badner, N. H., Komar, W. E., Fancourt-Smith, P. F., McEwen, J. A., Warriner, C. B., Moore, R., Rosenblatt, M., Merai, B., Robalino, J., Shevde, K., Bryk, D., McCormack, J. P., Levine, M., Forster-Coull, J., Stasiuk, R. B. P., Jenkins, L. C., Chen, Kunzhou, Pan, Jianhui, Ji, Xuan, Vaidya, D., Tetzlaff, J. E., Baird, B. A., Yoon, H. J., Wood, G., Simpson, T., Pillow, K. J., Lampe, K. M., Hansen, L. M., Foldvari, M., Courtice, I. D., MacLeod, B. A., Panos L., Lawson S., Koren G., Volgyesi, G. A., Kolesar, R., Wolf, G. L., Sidebotham, G. W., Sprung, J., Gamulin, S., Bosnjak, Z. J., Kampine, J. P., Doyle, D. John, Harioka, T., Sone, T., Kakuyama, M., Miyake, C., Toda, H., Sosis, M., Oka, T., Ohwada, T., Kochi, A., Mizuguchi, T., Kay, J. C., Beauchamp, R. J., Mazer, C. D., Inada, E., Iwahashi, K., Aoki, K., Takanashi, S., Kohama, M., Aoki, Y., Poole, L., Murphy, J. T., Moffitt, E. A., Jolly, D., Finegan, B. A., Beach, J., Gulamhusein, S., Vincent, D., Sullivan, P. J., Martineau, R. J., Miller, D. R., Lewis, P., Staniland, J., Cuppage, A., Davies, J. M., Rose, D. K., Cohen, M. M., Rogers, K. H., Gellner, D., Duncan, P. G., Johnson, J. A., Cohen, J. A., Boisvenu, G., Haley, L. D., Parlow, J. L., Cervenko, F. W., Dillon, F., Harwood, T., Kolesar, R., Volgyesi, G., Reid, C. W., Samson, B., Beattie, W. S., Goldsmith, C. H., Sims, C. H., Welborn, L. G., Hannallah, R. S., Higgins, T., Fink, R., Luban, N., Murray, D. J., Forbes, R. B., Mehta, M., Dull, D. L., Horimoto, Y., Naide, M., Schaefer, J. D., Bonn, G. E., Rhine, E. J., MacNeill, H. B., Ménard, E. A., Roberts, D. J., Komocar, L., Kay, J., Chevrier, R., Marsh, B. J., Morton, N. S., White, M., Kenny, G. N. C., Yamashita, M., Tsuji, M., Malviya, S., Swartz, J., Brown, K. A., Holtby, H., Ein, S., Shandling, B., Smith, M. F., Beauprie, I. G., Clark, A. G., Keith, I. C., Spence, D., Ogata, Hiromaru, Midorikawa, Yukio, Doyle, D. John, Teves, Leonides Y., Jhawar, Balraj S., Kawamura, Takae, Wakusawa, Reiji, Hackmann, T., Steward, D. J., Maltby, J. R., Loken, R. G., Watson, N. C., Kubota, Tatsuya, Katano, Toshio, Yoshizawa, Mutsumi, Ohtake, Kazuei, Onodera, Fumio, Yoshitake, S., Matsumoto, S., Miyakawa, H., Takahashi, T., Kitano, T., Iwasaka, H., Hayano, Y., Noguchi, T., Taniguchi, K., Honda, N., Koyama, K., Takahashi, J., Ochiai, R., Takeda, J., Nagano, M., Rolbin, S., Hew, E., Morningstar, B., Mahesh, K., Yukioka, H., Fujimori, M., Siriwardhana, S. A., Kawas, A., Yates, S., Gulden, H., Upton, J. M., Giesecke, A. H., Suzuki, H., Maru, E., Fujita, M., Pagliarello, G., Simons, J., Irita, K., Shafiq, J., Tareen, F. M., Yoshitake, J., Suderman, V. S., Crosby, E. T., Mallon, J. S., Dunn, G. L., Hatano, Y., Nakamura, K., Nishiwada, M., Mori, Kenjiro, Pounder, D. R., Blackstock, D., Steward, D., Kumagai, M., Takinami, M., Tanaka, S., Shudo, Y., Amaki, Y., Kobayashi, K., Jansen, G. F. A., Kedaria, M., Zuurmond, W. W. A., Hartley, E., St. Louis, P., Rybczynski, J., McLeod, M. E., Byrick, R. J., Mullen, J. Brendan, Wong, P. Y., Wigglesworth, D., Kay, J. Colin, Swartz, J. S., Gold, M., Braude, B. M., Dolovich, J., Gilmour, R. F., Sutherland, L. R., O’Connor, G., Riding, K., Laird, B., Riou, S., Gross, Michael, Tang, T., Halpern, S. H., Roy, A. G., Côté, J. J., Lindblad, T., Buckley, D. N., Oxom, D. C., Whatley, G. S., Knox, J. W. D., Hooper, J. G. V., Dolman, J., Faneourt-Smith, P. F., Torsher, L., Gao, Yuhui, Chai, Xiaoqing, O’Leary, G., Qureshi, S. A., Laganiere, S., McGilveray, I., Boylan, J. F., Hassard, P., Teasdale, S. J., Kapnoudhis, P., Vaghadia, H., Turnbull, K. M., Villeneuve, E., Buluran, J., Amyot, Y., Tanguay, M., Pharm, B., Beique, G., Sidi, A., Rush, W., Clanachan, A. S., Duke, P. C., Leroux, M., Corne, R., Patton, N., Greenberg, D., Parrott, J., Desjardins, P., Merchant R. N., Brown W. F., Watson B. V., Burrows, F. A., Tatman, D. J., Starr, J. M., Symreng, T., Kall, R. I., Schweiger, I. M., Finlayson, D. C., Weisel, R. D., Ivanov, J., Mickle, D. A., Fuller, John, Lu, Grant, Dain, Steven, McLean, R. F., Noble, W. H., Kolton, M., Newfield, A. M., Lipton, J. M., Ide, T., Isono, S., Kochi, T., Izumi, Y., Erian, R. F., Stafford-Smith, M., Yamada, M., Johnson, D., Hurst, T., Mayers, I., Tsuda, Takako, Takeuchi, Mikio, Ishikawa, Kiyoshi, Ando, Hiroshi, Hanamura, Yasunori, Takasu, Hiroe, Hiyama, A., and Cardiac Anaesthesia Research Group

Published
1990
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30. Associations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traits

Author

Harris, S.E., Corley, J., Wojczynski, M.K., Nauck, M., Levy, D., Gu, C., Sorensen, T.I.A., Noordam, R., Guo, X., Hill, W.D., Chen, Y.-D.I., Liu, C., Yao, J., Kraja, A.T., Daw, E.W., Irvin, M.R., Christensen, C., Newman, A.B., Hansen, T., Hudson, G., Zeng, D., Wu, H., Uitterlinden, A.G., Wareham, N.J., Perls, T.T., Grarup, N., Broeckel, U., Luan, J., Fu, M., Hemani, G., de Mutsert, R., Lin, S.J., Wilson, J.G., Jorgensen, M.E., Witte, D.R., Have, C.T., Ribel-Madsen, R., Wang, Y., Love-Gregory, L.D., Bowden, D.W., Province, M.A., Rotter, J.I., Taylor, A.M., Hunt, S.C., Thyagarajan, B., Goodarzi, M.O., Ridker, P.M., Torp-Pedersen, C., Ligthart, S., Starr, J.M., Feitosa, M.F., Arnett, D.K., de Haan, H.G., Jorgensen, T., Weeke, P.E., Graff, M., de las Fuentes, L., Justice, A.E., Hayward, C., Kerrison, N.D., Pedersen, O., Bonnelykke, K., Perry, J.A., Fetterman, J.L., Hai, Y., Malik, A.N., Vestergaard, H., Cropp, C.D., Ryan, K.A., Christensen, K., The Population Sciences Branch, NHLBI/NIH, Armasu, S.M., Langenberg, C., Forouhi, N.G., Yang, W., Teumer, A., Rodriguez, S., Kardia, S.L.R., Qi, Q., Becker, D.M., Baranski, T.J., Yanek, L.R., Rao, D.C., Fernandez, E.P., Lin, K.-H., Li-Gao, R., Sofer, T., Nohr, E.A., Larson, N.B., Sheu, W.H.-H., Elliott, P., An, P., Schnurr, T.M., Gu, Z., Taylor, K.D., Davies, G., Kilpelainen, T.O., Lee, W.-J., Patki, A., Barve, R.A., Brandslund, I., Sandow, K., Weiss, S., Wang, L., Stergiakouli, E., Mathias, R.A., Ghanbari, M., Tiwari, H.K., Rivadeneira, F., Davila-Roman, V.G., de Andrade, M., North, K.E., Richardson, T.G., Horta, B.L., Bielinski, S.J., Linneberg, A., Young, K., Argos, M., Dehghan, A., Chasman, D.I., Mook-Kanamori, D.O., Vaidya, D., Petersmann, A., Scott, R.A., Meigs, J.B., Ahluwalia, T.S., Gao, H., Rosendaal, F.R., Chakravarti, A., van Heemst, D., Cox, S.R., Williams, C., Pankow, J., Giulianini, F., Weir, B.S., Jonsson, A.E., Hartwig, F.P., Rohde, R., Ikram, M.A., Homuth, G., Lee, J.H., Deary, I.J., Erzurumluoglu, A.M., Chu, A.Y., Emery, L.S., Franco, O.H., Ong, K.K., Arking, D.E., Loos, R.J.F., Tzoulaki, I., Pattie, A., Timpson, N.J., and Turner, S.T.

Abstract

Mitochondria (MT), the major site of cellular energy production, are under dual genetic control by 37 mitochondrial DNA (mtDNA) genes and numerous nuclear genes (MT-nDNA). In the CHARGEmtDNA+ Consortium, we studied genetic associations of mtDNA and MT-nDNA associations with body mass index (BMI), waist-hip-ratio (WHR), glucose, insulin, HOMA-B, HOMA-IR, and HbA1c. This 45-cohort collaboration comprised 70,775 (insulin) to 170,202 (BMI) pan-ancestry individuals. Validation and imputation of mtDNA variants was followed by single-variant and gene-based association testing. We report two significant common variants, one in MT-ATP6 associated (p ≤ 5E−04) with WHR and one in the D-loop with glucose. Five rare variants in MT-ATP6, MT-ND5, and MT-ND6 associated with BMI, WHR, or insulin. Gene-based meta-analysis identified MT-ND3 associated with BMI (p ≤ 1E−03). We considered 2,282 MT-nDNA candidate gene associations compiled from online summary results for our traits (20 unique studies with 31 dataset consortia's genome-wide associations [GWASs]). Of these, 109 genes associated (p ≤ 1E−06) with at least 1 of our 7 traits. We assessed regulatory features of variants in the 109 genes, cis- and trans-gene expression regulation, and performed enrichment and protein-protein interactions analyses. Of the identified mtDNA and MT-nDNA genes, 79 associated with adipose measures, 49 with glucose/insulin, 13 with risk for type 2 diabetes, and 18 with cardiovascular disease, indicating for pleiotropic effects with health implications. Additionally, 21 genes related to cholesterol, suggesting additional important roles for the genes identified. Our results suggest that mtDNA and MT-nDNA genes and variants reported make important contributions to glucose and insulin metabolism, adipocyte regulation, diabetes, and cardiovascular disease.

Published
2019
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32. Sex Hormones and Change in N-Terminal Pro-B-Type Natriuretic Peptide Levels: The Multi-Ethnic Study of Atherosclerosis

Author

Ying, W, Zhao, D, Ouyang, P, Subramanya, V, Vaidya, D, Ndumele, CE, Sharma, K, Shah, SJ, Heckbert, SR, Lima, JA, deFilippi, CR, Budoff, MJ, Post, WS, and Michos, ED

Subjects
Male, Aging, Clinical Sciences, Brain, Middle Aged, Atherosclerosis, Cardiovascular, Estrogen, Peptide Fragments, Paediatrics and Reproductive Medicine, Endocrinology & Metabolism, Cross-Sectional Studies, Sex Factors, Heart Disease, Good Health and Well Being, Natriuretic Peptide, Clinical Research, Humans, Female, cardiovascular diseases, Longitudinal Studies, Prospective Studies, Gonadal Steroid Hormones, hormones, hormone substitutes, and hormone antagonists, Aged
Abstract

Context:Sex hormones may influence sex differences in cardiovascular disease (CVD). N-terminal pro-B-type natriuretic peptide (NT-proBNP), a predictor of CVD, is higher in women than men, which may relate to sex hormones. Objective:To evaluate whether total testosterone (T), bioavailable T, free T, estradiol, dehydroepiandrosterone (DHEA), and SHBG are associated with NT-proBNP. Design:Cohort study. Participants:Cross-sectional sample included 2371 postmenopausal women and 2688 men free of CVD, of which 2041 women and 2348 men were included longitudinally. Main Outcome Measures:NT-proBNP at baseline (2000 to 2002) and one or more repeat NT-proBNPs (through 2012). Analyses adjusted for CVD risk factors. Results:Women had higher NT-proBNP than men (median 79.9 vs 38.5 pg/mL). Cross-sectionally, higher bioavailable T, free T, DHEA, and lower SHBG levels were independently associated with lower NT-proBNP among both women and men (all P < 0.05). Higher total T in women and estradiol in men were also associated with lower NT-proBNP (both P < 0.05). Longitudinally, in women, higher total T, bioavailable T, free T, DHEA, and lower estradiol and SHBG were associated with greater 10-year increase in NT-proBNP (all P < 0.05). In men, higher free T and estradiol were associated with greater NT-proBNP increase (both P < 0.05). Conclusions:A more androgenic sex hormone pattern was inversely associated with NT-proBNP cross-sectionally and may contribute to sex differences in NT-proBNP. Longitudinally, a more androgenic sex hormone pattern was associated with greater increase in NT-proBNP in women, which may reflect a mechanism for CVD risk after menopause.

Published
2018
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36. Assessment of geothermal water quality for industrial and irrigation purposes in the Unai geothermal field, Gujarat, India

Author

Shah, M., Sircar, A., Varsada, R., Vaishnani, S., Savaliya, U., Faldu, M., Vaidya, D., Bhattacharya, Prosun, Shah, M., Sircar, A., Varsada, R., Vaishnani, S., Savaliya, U., Faldu, M., Vaidya, D., and Bhattacharya, Prosun

Abstract

Nowadays, a spotlight on the direct manipulation of water from the geothermal fields is laid for manifold applications. This manuscript discusses the utilization of water produced from geothermal wells for irrigation and industrial purposes. In order to identify the suitability of the water for the above mentioned uses, various hydrochemical parameters were evaluated. Samples were collected from three geothermal well sites from Unai village, a prominent geothermal field situated in Navsari district, Gujarat, India. The hydrochemistry of the samples collected from hot spring (depth 30–45 m) was studied and samples were examined by calculating different parameters. The complete study was done individually for both industrial and irrigational uses of geothermal water. The mean surface temperature of the water is 55 °C and average pH of the sample studied is 8.12. The key Water Quality Indices (WQI) such as Langelier Saturation Index (LSI), Ryznar Stability Index (RSI), Puckorius Scaling Index (PSI) and Larson-Skold Index (LS) were examined for industrial utilization and the key indices like Sodium Absorption Ratio (SAR), Sodium Percentage (SP), Kelly Ratio (KR) Residual Sodium Carbonate (RSC) and Permeability Index (PI) were examined for irrigational utilization of geothermal water. LSI and RSI values show that carbonate and bicarbonate concentration is in the desirable range, however, LS (15.09, 13.54) is very high which indicates higher Cl- content. High value of indices such as SAR, KR, and SP points out the increased concentration of Na+ in the water sample. The results of this study would help the end users to identify the necessary water-treatments before utilizing the water for industrial and irrigation purposes in the study area., QC 20181116

Published
2019
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39. Plasma-assisted As implants for effective work function modulation of TiN/HfO2 gate stacks on germanium

Author

KOTHARI, S, VAIDYA, D, NEJAD, H, VARIAM, N, GANGULY, S, and LODHA, S

Abstract

The plasma assisted As doping (PLAD) technique is used to demonstrate multiple flatband voltages (multi-V-fb) on TiN/HfO2 Ge gate stacks for n-FinFET applications. Through detailed studies with varying doses, implant energies, and TiN cap thicknesses, we show that the PLAD As technique can be used to obtain effective work function (EWF) modulation from the near midgap to the conduction band edge (up to 280 meV) of Ge, a key technological requirement for multi-threshold voltage (V-T) Ge n-FinFETs. Furthermore, there is no deterioration of key gate stack parameters such as gate leakage, effective oxide thickness, and gate/channel interface trap densities. From secondary ion mass spectroscopy data, we attribute the tuning of EWF to As accumulation and interfacial dipole formation at the TiN/HfO2 interface. The experimental observations are reinforced by ab initio simulations of near-interface As substitutions at the TiN/HfO2 interface. As substitution at N sites near the interface reduces the EWF, making it more suitable for n-MOS applications. Published by AIP Publishing.

Published
2018
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40. Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African ancestry anthropometry genetics consortium

Author

Ng, MCY, Graff, M, Lu, Y, Justice, AE, Mudgal, P, Liu, CT, Young, K, Yanek, LR, Feitosa, MF, Wojczynski, MK, Rand, K, Brody, JA, Cade, BE, Dimitrov, L, Duan, Q, Guo, X, Lange, LA, Nalls, MA, Okut, H, Tajuddin, SM, Tayo, BO, Vedantam, S, Bradfield, JP, Chen, G, Chen, WM, Chesi, A, Irvin, MR, Padhukasahasram, B, Smith, JA, Zheng, W, Allison, MA, Ambrosone, CB, Bandera, EV, Bartz, TM, Berndt, SI, Bernstein, L, Blot, WJ, Bottinger, EP, Carpten, J, Chanock, SJ, Chen, YDI, Conti, DV, Cooper, RS, Fornage, M, Freedman, BI, Garcia, M, Goodman, PJ, Hsu, YHH, Hu, J, Huff, CD, Ingles, SA, John, EM, Kittles, R, Klein, E, Li, J, McKnight, B, Nayak, U, Nemesure, B, Ogunniyi, A, Olshan, A, Press, MF, Rohde, R, Rybicki, BA, Salako, B, Sanderson, M, Shao, Y, Siscovick, DS, Stanford, JL, Stevens, VL, Stram, A, Strom, SS, Vaidya, D, Witte, JS, Yao, J, Zhu, X, Ziegler, RG, Zonderman, AB, Adeyemo, A, Ambs, S, Cushman, M, Faul, JD, Hakonarson, H, Levin, AM, Nathanson, KL, and Ware, EB

Abstract

© 2017 Public Library of Science. All rights reserved. Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMIfrom the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus (TCF7L2/HABP2) for WHRadjBMIand eight previously established loci at P < 5×10−8: seven for BMI, and one for WHRadjBMIin African ancestry individuals. An additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMIwhen combined with European GWAS. In the sex-stratified analyses, we identified three novel loci for BMI (INTS10/LPL and MLC1 in men, IRX4/IRX2 in women) and four for WHRadjBMI(SSX2IP, CASC8, PDE3B and ZDHHC1/HSD11B2 in women) in individuals of African ancestry or both African and European ancestry. For four of the novel variants, the minor allele frequency was low (

Published
2017
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45. Metabolically Healthy Obesity, Transition to Metabolic Syndrome, and Cardiovascular Risk

Author

Mongraw-Chaffin, M, Foster, MC, Anderson, CAM, Burke, GL, Haq, N, Kalyani, RR, Ouyang, P, Sibley, CT, Tracy, R, Woodward, M, Vaidya, D, Mongraw-Chaffin, M, Foster, MC, Anderson, CAM, Burke, GL, Haq, N, Kalyani, RR, Ouyang, P, Sibley, CT, Tracy, R, Woodward, M, and Vaidya, D

Abstract

Background: Debate over the cardiometabolic risk associated with metabolically healthy obesity (MHO) continues. Many studies have investigated this relationship by examining MHO at baseline with longitudinal follow-up, with inconsistent results. Objectives: The authors hypothesized that MHO at baseline is transient and that transition to metabolic syndrome (MetS) and duration of MetS explains heterogeneity in incident cardiovascular disease (CVD) and all-cause mortality. Methods: Among 6,809 participants of the MESA (Multi-Ethnic Study of Atherosclerosis) the authors used Cox proportional hazards and logistic regression models to investigate the joint association of obesity (≥30 kg/m 2 ) and MetS (International Diabetes Federation consensus definition) with CVD and mortality across a median of 12.2 years. We tested for interaction and conducted sensitivity analyses for a number of conditions. Results: Compared with metabolically healthy normal weight, baseline MHO was not significantly associated with incident CVD; however, almost one-half of those participants developed MetS during follow-up (unstable MHO). Those who had unstable MHO had increased odds of CVD (odds ratio [OR]: 1.60; 95% confidence interval [CI]: 1.14 to 2.25), compared with those with stable MHO or healthy normal weight. Dose response for duration of MetS was significantly and linearly associated with CVD (1 visit with MetS OR: 1.62; 95% CI: 1.27 to 2.07; 2 visits, OR: 1.92; 95% CI: 1.48 to 2.49; 3+ visits, OR: 2.33; 95% CI: 1.89 to 2.87; p value for trend <0.001) and MetS mediated approximately 62% (44% to 100%) of the relationship between obesity at any point during follow-up and CVD. Conclusions: Metabolically healthy obesity is not a stable or reliable indicator of future risk for CVD. Weight loss and lifestyle management for CVD risk factors should be recommended to all individuals with obesity.

Published
2018

46. Genetic Determinants of Circulating Estrogen Levels and Evidence of a Causal Effect of Estradiol on Bone Density in Men

Author

Eriksson, A.L. (Anna L.), Perry, J.R.B. (John R B), Coviello, A.D. (Andrea), Delgado, G., Ferrucci, L. (Luigi), Hoffman, A.R. (Andrew R.), Huhtaniemi, I.T. (I.), Ikram, M.A. (Arfan), Karlsson, M. (Magnus), Kleber, M.E. (Marcus), Laughlin, G.A. (Gail A.), Liu, Y. (YongMei), Lorentzon, M. (Mattias), Lunetta, K.L. (Kathryn), Mellström, D. (Dan), Murabito, J. (Joanne), Murray, A. (Anna), Nethander, M. (Maria), Nielson, C. (Carrie), Prokopenko, I. (Inga), Pye, S.R. (Stephen), Raffel, L.J. (Leslie J.), Rivadeneira, F. (Fernando), Srikanth, P. (Priya), Stolk, L. (Lisette), Teumer, A. (Alexander), Travison, T.G. (Thomas G.), Uitterlinden, A.G. (André), Vaidya, D. (Dhananjay), Vanderschueren, D. (Dirk), Zmuda, J. (Joseph), März, W. (Winfried), Orwoll, E.S. (Eric), Ouyang, P. (Pamela), Vandenput, L. (Liesbeth), Wu, F.C.W. (Frederick C W), de Jong, F.H. (Frank H.), Bhasin, S. (Shalender), Kiel, D.P. (Douglas P.), Ohlsson, C. (Claes), Eriksson, A.L. (Anna L.), Perry, J.R.B. (John R B), Coviello, A.D. (Andrea), Delgado, G., Ferrucci, L. (Luigi), Hoffman, A.R. (Andrew R.), Huhtaniemi, I.T. (I.), Ikram, M.A. (Arfan), Karlsson, M. (Magnus), Kleber, M.E. (Marcus), Laughlin, G.A. (Gail A.), Liu, Y. (YongMei), Lorentzon, M. (Mattias), Lunetta, K.L. (Kathryn), Mellström, D. (Dan), Murabito, J. (Joanne), Murray, A. (Anna), Nethander, M. (Maria), Nielson, C. (Carrie), Prokopenko, I. (Inga), Pye, S.R. (Stephen), Raffel, L.J. (Leslie J.), Rivadeneira, F. (Fernando), Srikanth, P. (Priya), Stolk, L. (Lisette), Teumer, A. (Alexander), Travison, T.G. (Thomas G.), Uitterlinden, A.G. (André), Vaidya, D. (Dhananjay), Vanderschueren, D. (Dirk), Zmuda, J. (Joseph), März, W. (Winfried), Orwoll, E.S. (Eric), Ouyang, P. (Pamela), Vandenput, L. (Liesbeth), Wu, F.C.W. (Frederick C W), de Jong, F.H. (Frank H.), Bhasin, S. (Shalender), Kiel, D.P. (Douglas P.), and Ohlsson, C. (Claes)

Abstract

Context: Serum estradiol (E2) and estrone (E1) levels exhibit substantial heritability.Objective: To investigate the genetic regulation of serum E2 and E1 in men.Design, Setting, and Participants: Genome-wide association study in 11,097 men of European origin from nine epidemiological cohorts.Main Outcome Measures: Genetic determinants of serum E2 and E1 levels.Results: Variants in/near CYP19A1 demonstrated the strongest evidence for association with E2, resolving to three independent signals. Two additional independent signals were found on the X chromosome; FAMily with sequence similarity 9, member B (FAM9B), rs5934505 (P = 3.4 × 10-8) and Xq27.3, rs5951794 (P = 3.1 × 10-10). E1 signals were found in CYP19A1 (rs2899472, P = 5.5 × 10-23), in Tripartite motif containing 4 (TRIM4; rs17277546, P = 5.8 × 10-14), and CYP11B1/B2 (rs10093796, P = 1.2 × 10-8). E2 signals in CYP19A1 and FAM9B were associated with bone mineral density (BMD). Mendelian randomization analysis suggested a causal effect of serum E2 on BMD in men. A 1 pg/mL genetically increased E2 was associated with a 0.048 standard deviation increase in lumbar spine BMD (P = 2.8 × 10-12). In men and women combined, CYP19A1 alleles associated with higher E2 levels were associated with lower degrees of insulin resistance.Conclusions: Our findings confirm that CYP19A1 is an important genetic regulator of E2 and E1 levels and strengthen the causal importance of E2 for bone health in men. We also report two independent loci on the X-chromosome for E2, and one locus each in TRIM4 and CYP11B1/B2, for E1.

Published
2018
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47. Genetic Determinants of Circulating Estrogen Levels and Evidence of a Causal Effect of Estradiol on Bone Density in Men

Author

Eriksson, AL, Perry, JRB, Coviello, AD, Delgado, GE, Ferrucci, L, Hoffman, AR, Huhtaniemi, IT, Ikram, Arfan, Karlsson, MK, Kleber, ME, Laughlin, GA, Liu, YM, Lorentzon, M, Lunetta, KL, Mellstrom, D, Murabito, JM, Murray, A, Nethander, M, Nielson, CM, Prokopenko, I, Pye, SR, Raffel, LJ, Rivadeneira, Fernando, Srikanth, P, Stolk, Lisette, Teumer, A, Travison, TG, Uitterlinden, André, Vaidya, D, Vanderschueren, D, Zmuda, JM, Marz, W, Orwoll, ES, Ouyang, P, Vandenput, L, Wu, FCW, Jong, Frank, Bhasin, S, Kiel, DP, Ohlsson, C, Eriksson, AL, Perry, JRB, Coviello, AD, Delgado, GE, Ferrucci, L, Hoffman, AR, Huhtaniemi, IT, Ikram, Arfan, Karlsson, MK, Kleber, ME, Laughlin, GA, Liu, YM, Lorentzon, M, Lunetta, KL, Mellstrom, D, Murabito, JM, Murray, A, Nethander, M, Nielson, CM, Prokopenko, I, Pye, SR, Raffel, LJ, Rivadeneira, Fernando, Srikanth, P, Stolk, Lisette, Teumer, A, Travison, TG, Uitterlinden, André, Vaidya, D, Vanderschueren, D, Zmuda, JM, Marz, W, Orwoll, ES, Ouyang, P, Vandenput, L, Wu, FCW, Jong, Frank, Bhasin, S, Kiel, DP, and Ohlsson, C

Published
2018

48. A bivariate genome-wide approach to metabolic syndrome: STAMPEED consortium

Author

Kraja, A, Vaidya, D, Pankow, J, Goodarzi, M, Assimes, T, Kullo, I, Sovio, U, Mathias, R, Sun, Y, Franceschini, N, Absher, D, Li, G, Zhang, Q, Feitosa, M, Glazer, N, Haritunians, T, Hartikainen, A, Knowles, J, North, K, Iribarren, C, Kral, B, Yanek, L, O'Reilly, P, McCarthy, M, and Jaquish, C

Abstract

OBJECTIVE The metabolic syndrome (MetS) is defined as concomitant disorders of lipid and glucose metabolism, central obesity, and high blood pressure, with an increased risk of type 2 diabetes and cardiovascular disease. This study tests whether common genetic variants with pleiotropic effects account for some of the correlated architecture among five metabolic phenotypes that define MetS. RESEARCH DESIGN AND METHODS Seven studies of the STAMPEED consortium, comprising 22,161 participants of European ancestry, underwent genome-wide association analyses of metabolic traits using a panel of ∼2.5 million imputed single nucleotide polymorphisms (SNPs). Phenotypes were defined by the National Cholesterol Education Program (NCEP) criteria for MetS in pairwise combinations. Individuals exceeding the NCEP thresholds for both traits of a pair were considered affected. RESULTS Twenty-nine common variants were associated with MetS or a pair of traits. Variants in the genes LPL, CETP, APOA5 (and its cluster), GCKR (and its cluster), LIPC, TRIB1, LOC100128354/MTNR1B, ABCB11, and LOC100129150 were further tested for their association with individual qualitative and quantitative traits. None of the 16 top SNPs (one per gene) associated simultaneously with more than two individual traits. Of them 11 variants showed nominal associations with MetS per se. The effects of 16 top SNPs on the quantitative traits were relatively small, together explaining from ∼9% of the variance in triglycerides, 5.8% of high-density lipoprotein cholesterol, 3.6% of fasting glucose, and 1.4% of systolic blood pressure. CONCLUSIONS Qualitative and quantitative pleiotropic tests on pairs of traits indicate that a small portion of the covariation in these traits can be explained by the reported common genetic variants.

Published
2016

49. Real-time transmission of 16 Tb/s over 1020km using 200Gb/s CFP2-DCO

Author

Zhang, H., primary, Zhu, B., additional, Park, S., additional, Doerr, C., additional, Aydinlik, M., additional, Geyer, J., additional, Pfau, T., additional, Pendock, G., additional, Aroca, R., additional, Liu, F., additional, Rasmussen, C., additional, Mikkelsen, B., additional, Borel, P. I., additional, Geisler, T., additional, Jensen, R., additional, Peckham, D. W., additional, Lingle, R., additional, Vaidya, D., additional, Yan, M. F., additional, Wisk, P. W., additional, and DiGiovanni, D. J., additional

Published
2018
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50. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

Author

Ehret, G.B. Ferreira, T. Chasman, D.I. Jackson, A.U. Schmidt, E.M. Johnson, T. Thorleifsson, G. Luan, J. Donnelly, L.A. Kanoni, S. Petersen, A.-K. Pihur, V. Strawbridge, R.J. Shungin, D. Hughes, M.F. Meirelles, O. Kaakinen, M. Bouatia-Naji, N. Kristiansson, K. Shah, S. Kleber, M.E. Guo, X. Lyytikäinen, L.-P. Fava, C. Eriksson, N. Nolte, I.M. Magnusson, P.K. Salfati, E.L. Rallidis, L.S. Theusch, E. Smith, A.J.P. Folkersen, L. Witkowska, K. Pers, T.H. Joehanes, R. Kim, S.K. Lataniotis, L. Jansen, R. Johnson, A.D. Warren, H. Kim, Y.J. Zhao, W. Wu, Y. Tayo, B.O. Bochud, M. Absher, D. Adair, L.S. Amin, N. Arking, D.E. Axelsson, T. Baldassarre, D. Balkau, B. Bandinelli, S. Barnes, M.R. Barroso, I. Bevan, S. Bis, J.C. Bjornsdottir, G. Boehnke, M. Boerwinkle, E. Bonnycastle, L.L. Boomsma, D.I. Bornstein, S.R. Brown, M.J. Burnier, M. Cabrera, C.P. Chambers, J.C. Chang, I.-S. Cheng, C.-Y. Chines, P.S. Chung, R.-H. Collins, F.S. Connell, J.M. Döring, A. Dallongeville, J. Danesh, J. De Faire, U. Delgado, G. Dominiczak, A.F. Doney, A.S.F. Drenos, F. Edkins, S. Eicher, J.D. Elosua, R. Enroth, S. Erdmann, J. Eriksson, P. Esko, T. Evangelou, E. Evans, A. Fall, T. Farrall, M. Felix, J.F. Ferrières, J. Ferrucci, L. Fornage, M. Forrester, T. Franceschini, N. Franco, O.H. Franco-Cereceda, A. Fraser, R.M. Ganesh, S.K. Gao, H. Gertow, K. Gianfagna, F. Gigante, B. Giulianini, F. Goel, A. Goodall, A.H. Goodarzi, M.O. Gorski, M. Gräßler, J. Groves, C.J. Gudnason, V. Gyllensten, U. Hallmans, G. Hartikainen, A.-L. Hassinen, M. Havulinna, A.S. Hayward, C. Hercberg, S. Herzig, K.-H. Hicks, A.A. Hingorani, A.D. Hirschhorn, J.N. Hofman, A. Holmen, J. Holmen, O.L. Hottenga, J.-J. Howard, P. Hsiung, C.A. Hunt, S.C. Ikram, M.A. Illig, T. Iribarren, C. Jensen, R.A. Kähönen, M. Kang, H.M. Kathiresan, S. Keating, B.J. Khaw, K.-T. Kim, Y.K. Kim, E. Kivimaki, M. Klopp, N. Kolovou, G. Komulainen, P. Kooner, J.S. Kosova, G. Krauss, R.M. Kuh, D. Kutalik, Z. Kuusisto, J. Kvaløy, K. Lakka, T.A. Lee, N.R. Lee, I.-T. Lee, W.-J. Levy, D. Li, X. Liang, K.-W. Lin, H. Lin, L. Lindström, J. Lobbens, S. Männistö, S. Müller, G. Müller-Nurasyid, M. Mach, F. Markus, H.S. Marouli, E. McCarthy, M.I. McKenzie, C.A. Meneton, P. Menni, C. Metspalu, A. Mijatovic, V. Moilanen, L. Montasser, M.E. Morris, A.D. Morrison, A.C. Mulas, A. Nagaraja, R. Narisu, N. Nikus, K. O'Donnell, C.J. O'Reilly, P.F. Ong, K.K. Paccaud, F. Palmer, C.D. Parsa, A. Pedersen, N.L. Penninx, B.W. Perola, M. Peters, A. Poulter, N. Pramstaller, P.P. Psaty, B.M. Quertermous, T. Rao, D.C. Rasheed, A. Rayner, N.W. Renström, F. Rettig, R. Rice, K.M. Roberts, R. Rose, L.M. Rossouw, J. Samani, N.J. Sanna, S. Saramies, J. Schunkert, H. Sebert, S. Sheu, W.H.-H. Shin, Y.-A. Sim, X. Smit, J.H. Smith, A.V. Sosa, M.X. Spector, T.D. Stančáková, A. Stanton, A.V. Stirrups, K.E. Stringham, H.M. Sundstrom, J. Swift, A.J. Syvänen, A.-C. Tai, E.-S. Tanaka, T. Tarasov, K.V. Teumer, A. Thorsteinsdottir, U. Tobin, M.D. Tremoli, E. Uitterlinden, A.G. Uusitupa, M. Vaez, A. Vaidya, D. Van Duijn, C.M. Van Iperen, E.P.A. Vasan, R.S. Verwoert, G.C. Virtamo, J. Vitart, V. Voight, B.F. Vollenweider, P. Wagner, A. Wain, L.V. Wareham, N.J. Watkins, H. Weder, A.B. Westra, H.-J. Wilks, R. Wilsgaard, T. Wilson, J.F. Wong, T.Y. Yang, T.-P. Yao, J. Yengo, L. Zhang, W. Zhao, J.H. Zhu, X. Bovet, P. Cooper, R.S. Mohlke, K.L. Saleheen, D. Lee, J.-Y. Elliott, P. Gierman, H.J. Willer, C.J. Franke, L. Hovingh, G.K. Taylor, K.D. Dedoussis, G. Sever, P. Wong, A. Lind, L. Assimes, T.L. Njølstad, I. Schwarz, P.E.H. Langenberg, C. Snieder, H. Caulfield, M.J. Melander, O. Laakso, M. Saltevo, J. Rauramaa, R. Tuomilehto, J. Ingelsson, E. Lehtimäki, T. Hveem, K. Palmas, W. März, W. Kumari, M. Salomaa, V. Chen, Y.-D.I. Rotter, J.I. Froguel, P. Jarvelin, M.-R. Lakatta, E.G. Kuulasmaa, K. Franks, P.W. Hamsten, A. Wichmann, H.-E. Palmer, C.N.A. Stefansson, K. Ridker, P.M. Loos, R.J.F. Chakravarti, A. Deloukas, P. Morris, A.P. Newton-Cheh, C. Munroe, P.B.

Abstract

To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation. © 2016 Nature America, Inc. All rights reserved.

Published
2016

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