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52. Factors Influencing Fellowship Decision Making During Physical Medicine & Rehabilitation Residency.

Author

Yang, Aaron Jay, Haring, R. Sterling, Swenson, Theodora L., and Jain, Nitin B.

Subjects
*PHYSICAL medicine, *SCHOLARSHIPS, *INTERNSHIP programs, *DECISION making, *DESCRIPTIVE statistics, *REHABILITATION
Abstract

Previous surveys have demonstrated an increasing trend among graduating physiatry residents who desired to pursue a subspecialty fellowship. There has been sparse information on whether residents start their training with a subspecialty interest in mind and what factors influenced them to choose a fellowship. This article describes a prospective survey in the 2019–2020 academic year in which 175 responses were collected representing 65 (78.3%) of the 83 physical medicine and rehabilitation programs with graduating residents. Nearly 3 in 4 (73.7%, 129/175) reported matching into a fellowship, and among those, 79.8% (103/129) had matched into a pain, spine, or sports medicine fellowship. At the start of residency, 62.3% (109/175) were planning to pursue a fellowship, with 54.9% (96/175) planning to focus on either pain, sports, or spine medicine. Most respondents (72.2%) did not change their initial subspecialty focus during their residency training. Forty-six percent agreed that their anticipated subspecialty influenced their choice of residency program. The results of this survey demonstrate that most graduating residents are matriculating into fellowship training with pain, spine, and/or sports medicine being among the top choices. These results underscore the importance of subspecialty interests of trainees at the start of their residency and how training may influence their subspecialty interest. [ABSTRACT FROM AUTHOR]

Published
2021
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53. Calibration and postlaunch performance of the Meteor 3/TOMS instrument

Author

Jaross, G, Krueger, A, Cebula, R. P, Seftor, C, Hartmann, U, Haring, R, and Burchfield, D

Subjects
Instrumentation And Photography
Abstract

Prelaunch and postlaunch calibration results for the Meteor 3/total ozone mapping spectrometer (TOMS) instrument are presented here. Ozone amounts are retrieved from measurements of Earth albedo in the 312- to 380-nm range. The accuracy of albedo measurements is primarily tied to knowledge of the reflective properties of diffusers used in the calibrations and to the instrument's wavelength selection. These and other important prelaunch calibrations are presented. Their estimated accuracies are within the bounds necessary to determine column ozone to better than 1%. However, postlaunch validation results indicate some prelaunch calibration uncertainties may be larger than originally estimated. Instrument calibrations have been maintained postlaunch to within a corresponding 1% error in retrieved ozone. Onboard calibrations, including wavelength monitoring and a three-diffuser solar measurement system, are described and specific results are presented. Other issues, such as the effects of orbital precession on calibration and recent chopper wheel malfunctions, are also discussed.

Published
1995
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56. Conscious status is associated with the likelihood of trauma centre care and mortality in patients with moderate-to-severe traumatic brain injury

Author

AlSulaim, Hatim A., primary, Haring, R. Sterling, additional, Asemota, Anthony O., additional, Smart, Blair J., additional, Canner, Joseph K., additional, Ejaz, Aslam, additional, Efron, David T., additional, Velopulos, Catherine G., additional, Haut, Elliott R., additional, and Schneider, Eric B., additional

Published
2018
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60. In Reply

Author

Gupta, Avni, primary, Haring, R. Sterling, additional, and Schneider, Eric B., additional

Published
2017
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62. Occupational Variation in End-of-Life Care Intensity

Author

Hyder, Joseph A., primary, Haring, R. Sterling, additional, Sturgeon, Daniel, additional, Gazarian, Priscilla K., additional, Jiang, Wei, additional, Cooper, Zara, additional, Lipsitz, Stuart R., additional, Prigerson, Holly G., additional, and Weissman, Joel S., additional

Published
2017
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64. y New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

Author

Lu, YC, Day, FR, Gustafsson, S, Buchkovich, ML, Na, JB, Bataille, V, Cousminer, DL, Dastani, Z, Drong, AW, Esko, T, Evans, DM, Falchi, M, Feitosa, MF, Ferreira, T, Hedman, AK, Haring, R, Hysi, PG, Iles, MM, Justice, AE, Kanoni, S, Lagou, V, Li, R, Li, X, Locke, A, Lu, C, Magi, R, Perry, JRB, Pers, TH, Qi, QB, Sanna, M, Schmidt, EM, Scott, WR, Shungin, D, Teumer, A, Vinkhuyzen, AAE, Walker, RW, Westra, HJ, Zhang, MF, Zhang, WH, Zhao, JH, Zhu, ZH, Afzal, U, Ahluwalia, TS, Bakker, SJL, Bellis, C, Bonnefond, A, Borodulin, K, Buchman, AS, Cederholm, T, Choh, AC, Choi, HJ, Curran, JE, de Groot, LCPGM (Lisette), De Jager, PL, Dhonukshe-Rutten, RAM, Enneman, Anke, Eury, E, Evans, DS, Forsen, T, Friedrich, N, Fumeron, F, Garcia, ME, Gartner, S, Han, BG, Havulinna, AS, Hayward, C, Hernandez, D, Hillege, H, Ittermann, T, Kent, JW, Kolcic, I, Laatikainen, T, Lahti, J, Leach, IM, Lee, CG, Lee, JY, Liu, T, Liu, YF, Lobbens, S, Loh, M, Lyytikainen, LP, Medina-Gomez, C, Michaelsson, K, Nalls, MA, Nielson, CM, Oozageer, L, Pascoe, L, Paternoster, L, Polasek, O, Ripatti, S, Sarzynski, MA, Shin, CS, Narancic, NS, Spira, D, Srikanth, P, Steinhagen-Thiessen, E, Sung, YJ, Swart, KMA, Taittonen, L, Tanaka, T, Tikkanen, E, van der Velde, Nathalie, Schoor, NM, Verweij, N (Niek), Wright, AF, Yu, L, Zmuda, JM, Eklund, N, Forrester, T, Grarup, N, Jackson, AU, Kristiansson, K, Kuulasmaa, T, Kuusisto, J, Lichtner, P, Luan, JA, Mahajan, A, Mannisto, S, Palmer, CD, Ried, JS, Scott, RA, Stancakova, A, Wagner, PJ, Demirkan, Ayse, Doring, A, Gudnason, V, Kiel, DP, Kuhnel, B, Mangino, M, McKnight, B, Menni, C, O'Connell, JR, Oostra, Ben, Shuldiner, AR, Song, KJ, Vandenput, L, Duijn, Cornelia, Vollenweider, P, White, CC, Boehnke, M, Boettcher, Y, Cooper, RS, Forouhi, NG, Gieger, C, Grallert, H, Hingorani, A, Jorgensen, T, Jousilahti, P, Kivimaki, M, Kumari, M, Laakso, M, Langenberg, C, Linneberg, A, Luke, A, McKenzie, CA, Palotie, A, Pedersen, O, Peters, A, Strauch, K, Tayo, BO, Wareham, NJ, Bennett, DA, Bertram, L, Blangero, J, Bluher, M, Bouchard, C, Campbell, H, Cho, NH, Cummings, SR, Czerwinski, SA, Demuth, I, Eckardt, R, Eriksson, JG, Ferrucci, L, Franco Duran, OH, Froguel, P, Gansevoort, RT, Hansen, T, Harris, TB, Hastie, N, Heliovaara, M, Hofman, Bert, Jordan, JM, Jula, A, Kahonen, M, Kajantie, E, Knekt, PB, Koskinen, S, Kovacs, P, Lehtimaki, T, Lind, L, Liu, YM, Orwoll, ES, Osmond, C, Perola, M, Perusse, L, Raitakari, OT, Rankinen, T, Rao, DC, Rice, TK, Rivadeneira, Fernando, Rudan, I, Salomaa, V, Sorensen, TIA, Stumvoll, M, Tonjes, A, Towne, B, Tranah, GJ, Tremblay, A, Uitterlinden, André, van der Harst, P, Vartiainen, E, Viikari, JS, Vitart, V, Vohl, MC, Volzke, H, Walker, M, Wallaschofski, H, Wild, S, Wilson, JF, Yengo, L, Bishop, DT, Borecki, IB, Chambers, JC, Cupples, LA, Dehghan, Abbas, Deloukas, P, Fatemifar, G, Fox, C, Furey, TS, Franke, L, Han, JL, Hunter, DJ, Karjalainen, J, Karpe, F, Kaplan, RC, Kooner, JS, McCarthy, MI, Murabito, JM, Morris, AP, Bishop, JAN, North, KE, Ohlsson, C, Ong, KK, Prokopenko, I, Richards, JB, Schadt, EE, Spector, TD, Widen, E, Willer, CJ, Yang, Jiaqi, Ingelsson, E, Mohlke, KL, Hirschhorn, JN, Pospisilik, JA, Zillikens, M.C., Lindgren, C, Kilpelainen, TO, Loos, RJF, Lu, YC, Day, FR, Gustafsson, S, Buchkovich, ML, Na, JB, Bataille, V, Cousminer, DL, Dastani, Z, Drong, AW, Esko, T, Evans, DM, Falchi, M, Feitosa, MF, Ferreira, T, Hedman, AK, Haring, R, Hysi, PG, Iles, MM, Justice, AE, Kanoni, S, Lagou, V, Li, R, Li, X, Locke, A, Lu, C, Magi, R, Perry, JRB, Pers, TH, Qi, QB, Sanna, M, Schmidt, EM, Scott, WR, Shungin, D, Teumer, A, Vinkhuyzen, AAE, Walker, RW, Westra, HJ, Zhang, MF, Zhang, WH, Zhao, JH, Zhu, ZH, Afzal, U, Ahluwalia, TS, Bakker, SJL, Bellis, C, Bonnefond, A, Borodulin, K, Buchman, AS, Cederholm, T, Choh, AC, Choi, HJ, Curran, JE, de Groot, LCPGM (Lisette), De Jager, PL, Dhonukshe-Rutten, RAM, Enneman, Anke, Eury, E, Evans, DS, Forsen, T, Friedrich, N, Fumeron, F, Garcia, ME, Gartner, S, Han, BG, Havulinna, AS, Hayward, C, Hernandez, D, Hillege, H, Ittermann, T, Kent, JW, Kolcic, I, Laatikainen, T, Lahti, J, Leach, IM, Lee, CG, Lee, JY, Liu, T, Liu, YF, Lobbens, S, Loh, M, Lyytikainen, LP, Medina-Gomez, C, Michaelsson, K, Nalls, MA, Nielson, CM, Oozageer, L, Pascoe, L, Paternoster, L, Polasek, O, Ripatti, S, Sarzynski, MA, Shin, CS, Narancic, NS, Spira, D, Srikanth, P, Steinhagen-Thiessen, E, Sung, YJ, Swart, KMA, Taittonen, L, Tanaka, T, Tikkanen, E, van der Velde, Nathalie, Schoor, NM, Verweij, N (Niek), Wright, AF, Yu, L, Zmuda, JM, Eklund, N, Forrester, T, Grarup, N, Jackson, AU, Kristiansson, K, Kuulasmaa, T, Kuusisto, J, Lichtner, P, Luan, JA, Mahajan, A, Mannisto, S, Palmer, CD, Ried, JS, Scott, RA, Stancakova, A, Wagner, PJ, Demirkan, Ayse, Doring, A, Gudnason, V, Kiel, DP, Kuhnel, B, Mangino, M, McKnight, B, Menni, C, O'Connell, JR, Oostra, Ben, Shuldiner, AR, Song, KJ, Vandenput, L, Duijn, Cornelia, Vollenweider, P, White, CC, Boehnke, M, Boettcher, Y, Cooper, RS, Forouhi, NG, Gieger, C, Grallert, H, Hingorani, A, Jorgensen, T, Jousilahti, P, Kivimaki, M, Kumari, M, Laakso, M, Langenberg, C, Linneberg, A, Luke, A, McKenzie, CA, Palotie, A, Pedersen, O, Peters, A, Strauch, K, Tayo, BO, Wareham, NJ, Bennett, DA, Bertram, L, Blangero, J, Bluher, M, Bouchard, C, Campbell, H, Cho, NH, Cummings, SR, Czerwinski, SA, Demuth, I, Eckardt, R, Eriksson, JG, Ferrucci, L, Franco Duran, OH, Froguel, P, Gansevoort, RT, Hansen, T, Harris, TB, Hastie, N, Heliovaara, M, Hofman, Bert, Jordan, JM, Jula, A, Kahonen, M, Kajantie, E, Knekt, PB, Koskinen, S, Kovacs, P, Lehtimaki, T, Lind, L, Liu, YM, Orwoll, ES, Osmond, C, Perola, M, Perusse, L, Raitakari, OT, Rankinen, T, Rao, DC, Rice, TK, Rivadeneira, Fernando, Rudan, I, Salomaa, V, Sorensen, TIA, Stumvoll, M, Tonjes, A, Towne, B, Tranah, GJ, Tremblay, A, Uitterlinden, André, van der Harst, P, Vartiainen, E, Viikari, JS, Vitart, V, Vohl, MC, Volzke, H, Walker, M, Wallaschofski, H, Wild, S, Wilson, JF, Yengo, L, Bishop, DT, Borecki, IB, Chambers, JC, Cupples, LA, Dehghan, Abbas, Deloukas, P, Fatemifar, G, Fox, C, Furey, TS, Franke, L, Han, JL, Hunter, DJ, Karjalainen, J, Karpe, F, Kaplan, RC, Kooner, JS, McCarthy, MI, Murabito, JM, Morris, AP, Bishop, JAN, North, KE, Ohlsson, C, Ong, KK, Prokopenko, I, Richards, JB, Schadt, EE, Spector, TD, Widen, E, Willer, CJ, Yang, Jiaqi, Ingelsson, E, Mohlke, KL, Hirschhorn, JN, Pospisilik, JA, Zillikens, M.C., Lindgren, C, Kilpelainen, TO, and Loos, RJF

Abstract

To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P < 5 x 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.

Published
2016

68. EIGHT COMMON GENETIC VARIANTS ASSOCIATED WITH SERUM DHEAS LEVELS SUGGESTS A KEY ROLE IN AGEING MECHANISMS

Author

Zhai, G, Teumer, A, Stolk, L, Perry, JRB, Vandenput, L, Coviello, AD, Koster, A, Bandinelli, S, Bell, JT, Bhasin, S, Eriksson, J, Eriksson, A, Ernst, F, Ferrucci, L, Frayling, TM, Glass, D, Grundberg, E, Haring, R, Hedman, AK, Hofman, A, Kiel, DP, Kroemer, HK, Liu, Y, Lunetta, L, Lorentzon, M, Mangino, M, Melzer, D, Miljkovic, I, Nica, A, Vasan, RS, Small, KS, Soranzo, N, Uitterlinden, AG, Voelzke, H, Wilson, S, Zhuang, WV, Harris, T, Murabito, JM, Ohlsson, C, Murray, A, Jong, F, Spector, TD, and Wallaschofski, H

Published
2011

70. Prävalenz des Metabolischen Syndroms in Deutschland: Ergebnisse der Study of Health in Pomerania (SHIP)

Author

Schipf, S, Alte, D, Völzke, H, Friedrich, N, Haring, R, Lohmann, T, Rathmann, W, Nauck, M, Felix S, B, John, U, and Wallaschofski, H

Subjects
ddc: 610, Prävention, 610 Medical sciences, Medicine, SHIP, Metabolisches Syndrom
Abstract

Hintergrund: Internationale Studien zeigen eine Zunahme der Prävalenz des Metabolischen Syndroms (MetSyn) und eine Verschiebung zu einem jüngeren Manifestationsalter. Bevölkerungsbezogene Prävalenzschätzungen für Deutschland liegen aus dem Bundes-Gesundheitssurvey 1998 [for full text, please go to the a.m. URL], 54. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie (gmds)

Published
2009
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71. Association of non-alcoholic fatty liver disease with chronic kidney disease : a systematic review and meta-analysis

Author

Musso, G., Gambino, R., Tabibian, J.H., Ekstedt, Mattias, Kechagias, Stergios, Hamaguchi, M., Hultcrantz, R., Hagstrom, H., Yoon, S.K., Charatcharoenwitthaya, P., George, J., Barrera, F., Haflidadottir, S., Bjornsson, E.S., Armstrong, M.J., Hopkins, L.J., Gao, X., Francque, S., Verrijken, A., Yilmaz, Y., Lindor, K.D., Charlton, M., Haring, R., Lerch, M.M., Rettig, R., Volzke, H., Ryu, S., Li, G., Wong, L.L., Machado, M., Cortez-Pinto, H., Yasui, K., Cassader, M., Musso, G., Gambino, R., Tabibian, J.H., Ekstedt, Mattias, Kechagias, Stergios, Hamaguchi, M., Hultcrantz, R., Hagstrom, H., Yoon, S.K., Charatcharoenwitthaya, P., George, J., Barrera, F., Haflidadottir, S., Bjornsson, E.S., Armstrong, M.J., Hopkins, L.J., Gao, X., Francque, S., Verrijken, A., Yilmaz, Y., Lindor, K.D., Charlton, M., Haring, R., Lerch, M.M., Rettig, R., Volzke, H., Ryu, S., Li, G., Wong, L.L., Machado, M., Cortez-Pinto, H., Yasui, K., and Cassader, M.

Abstract

Background:Chronic kidney disease (CKD) is a frequent, under-recognized condition and a risk factor for renal failure and cardiovascular disease. Increasing evidence connects non-alcoholic fatty liver disease (NAFLD) to CKD. We conducted a meta-analysis to determine whether the presence and severity of NAFLD are associated with the presence and severity of CKD.Methods and Findings:English and non-English articles from international online databases from 1980 through January 31, 2014 were searched. Observational studies assessing NAFLD by histology, imaging, or biochemistry and defining CKD as either estimated glomerular filtration rate (eGFR) andlt;60 ml/min/1.73 m2 or proteinuria were included. Two reviewers extracted studies independently and in duplicate. Individual participant data (IPD) were solicited from all selected studies. Studies providing IPD were combined with studies providing only aggregate data with the two-stage method. Main outcomes were pooled using random-effects models. Sensitivity and subgroup analyses were used to explore sources of heterogeneity and the effect of potential confounders. The influences of age, whole-body/abdominal obesity, homeostasis model of insulin resistance (HOMA-IR), and duration of follow-up on effect estimates were assessed by meta-regression. Thirty-three studies (63,902 participants, 16 population-based and 17 hospital-based, 20 cross-sectional, and 13 longitudinal) were included. For 20 studies (61% of included studies, 11 cross-sectional and nine longitudinal, 29,282 participants), we obtained IPD. NAFLD was associated with an increased risk of prevalent (odds ratio [OR] 2.12, 95% CI 1.69-2.66) and incident (hazard ratio [HR] 1.79, 95% CI 1.65-1.95) CKD. Non-alcoholic steatohepatitis (NASH) was associated with a higher prevalence (OR 2.53, 95% CI 1.58-4.05) and incidence (HR 2.12, 95% CI 1.42-3.17) of CKD than simple steatosis. Advanced fibrosis was associated with a higher prevalence (OR 5.20, 95% CI 3.14-8.61) and

Published
2014
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72. Testosterone, sex hormone-binding globulin and the metabolic syndrome in men: an individual participant data meta-analysis of observational studies

Author

Brand, J.S., Rovers, M.M., Yeap, B.B., Schneider, H.J., Tuomainen, T.P., Haring, R., Corona, G., Onat, A., Maggio, M., Bouchard, C., Tong, P.C., Chen, R.Y., Akishita, M., Gietema, J.A., Gannage-Yared, M.H., Unden, A.L., Hautanen, A., Goncharov, N.P., Kumanov, P., Chubb, S.A., Almeida, O.P., Wittchen, H.U., Klotsche, J., Wallaschofski, H., Volzke, H., Kauhanen, J., Salonen, J.T., Ferrucci, L., Schouw, Y.T. van der, Brand, J.S., Rovers, M.M., Yeap, B.B., Schneider, H.J., Tuomainen, T.P., Haring, R., Corona, G., Onat, A., Maggio, M., Bouchard, C., Tong, P.C., Chen, R.Y., Akishita, M., Gietema, J.A., Gannage-Yared, M.H., Unden, A.L., Hautanen, A., Goncharov, N.P., Kumanov, P., Chubb, S.A., Almeida, O.P., Wittchen, H.U., Klotsche, J., Wallaschofski, H., Volzke, H., Kauhanen, J., Salonen, J.T., Ferrucci, L., and Schouw, Y.T. van der

Abstract

Contains fulltext : 136938.pdf (publisher's version ) (Open Access), BACKGROUND: Low total testosterone (TT) and sex hormone-binding globulin (SHBG) concentrations have been associated with the metabolic syndrome (MetS) in men, but the reported strength of association varies considerably. OBJECTIVES: We aimed to investigate whether associations differ across specific subgroups (according to age and body mass index (BMI)) and individual MetS components. DATA SOURCES: Two previously published meta-analyses including an updated systematic search in PubMed and EMBASE. STUDY ELIGIBILITY CRITERIA: Cross-sectional or prospective observational studies with data on TT and/or SHBG concentrations in combination with MetS in men. METHODS: We conducted an individual participant data meta-analysis of 20 observational studies. Mixed effects models were used to assess cross-sectional and prospective associations of TT, SHBG and free testosterone (FT) with MetS and its individual components. Multivariable adjusted odds ratios (ORs) and hazard ratios (HRs) were calculated and effect modification by age and BMI was studied. RESULTS: Men with low concentrations of TT, SHBG or FT were more likely to have prevalent MetS (ORs per quartile decrease were 1.69 (95% CI 1.60-1.77), 1.73 (95% CI 1.62-1.85) and 1.46 (95% CI 1.36-1.57) for TT, SHBG and FT, respectively) and incident MetS (HRs per quartile decrease were 1.25 (95% CI 1.16-1.36), 1.44 (95% 1.30-1.60) and 1.14 (95% 1.01-1.28) for TT, SHBG and FT, respectively). Overall, the magnitude of associations was largest in non-overweight men and varied across individual components: stronger associations were observed with hypertriglyceridemia, abdominal obesity and hyperglycaemia and associations were weakest for hypertension. CONCLUSIONS: Associations of testosterone and SHBG with MetS vary according to BMI and individual MetS components. These findings provide further insights into the pathophysiological mechanisms linking low testosterone and SHBG concentrations to cardiometabolic risk.

Published
2014

73. Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche

Author

Perry, J.R., Day, F., Elks, C.E., Sulem, P., Thompson, D.J., Ferreira, T., He, C., Chasman, D.I., Esko, T., Thorleifsson, G., Albrecht, E., Ang, W.Q., Corre, T., Cousminer, D.L., Feenstra, B., Franceschini, N., Ganna, A., Johnson, A.D., Kjellqvist, S., Lunetta, K.L., McMahon, G., Nolte, I.M., Paternoster, L., Porcu, E., Smith, A.V., Stolk, L., Teumer, A., Tsernikova, N., Tikkanen, E., Ulivi, S., Wagner, E.K., Amin, N., Bierut, L.J., Byrne, E.M., Hottenga, J.J., Koller, D.L., Mangino, M., Pers, T.H., Yerges-Armstrong, L.M., Zhao, J., Andrulis, I.L., Anton-Culver, H., Atsma, F., Bandinelli, S., Beckmann, M.W., Benitez, J., Blomqvist, C., Bojesen, S.E., Bolla, M.K., Bonanni, B., Brauch, H., Brenner, H., Buring, J.E., Chang-Claude, J., Chanock, S., Chen, J., Chenevix-Trench, G., Collee, J.M., Couch, F.J., Couper, D., Coviello, A.D., Cox, A, Czene, K., D'Adamo, P., Smith, G., Vivo, I. De, Demerath, E.W., Dennis, J., Devilee, P., Dieffenbach, A.K., Dunning, A.M., Eiriksdottir, G., Eriksson, J.G., Fasching, P.A., Ferrucci, L., Flesch-Janys, D., Flyger, H., Foroud, T., Franke, L., Garcia, M.E., Garcia-Closas, M., Geller, F., Geus, E.E. de, Giles, G.G., Gudbjartsson, D.F., Gudnason, V., Guenel, P., Guo, S., Hall, P., Hamann, U., Haring, R., Hartman, C.A., Heath, A.C., Hofman, A., Hooning, M.J., Hopper, J.L., Hu, F.B., Hunter, D.J., Karasik, D., Kiel, D.P., et al., Perry, J.R., Day, F., Elks, C.E., Sulem, P., Thompson, D.J., Ferreira, T., He, C., Chasman, D.I., Esko, T., Thorleifsson, G., Albrecht, E., Ang, W.Q., Corre, T., Cousminer, D.L., Feenstra, B., Franceschini, N., Ganna, A., Johnson, A.D., Kjellqvist, S., Lunetta, K.L., McMahon, G., Nolte, I.M., Paternoster, L., Porcu, E., Smith, A.V., Stolk, L., Teumer, A., Tsernikova, N., Tikkanen, E., Ulivi, S., Wagner, E.K., Amin, N., Bierut, L.J., Byrne, E.M., Hottenga, J.J., Koller, D.L., Mangino, M., Pers, T.H., Yerges-Armstrong, L.M., Zhao, J., Andrulis, I.L., Anton-Culver, H., Atsma, F., Bandinelli, S., Beckmann, M.W., Benitez, J., Blomqvist, C., Bojesen, S.E., Bolla, M.K., Bonanni, B., Brauch, H., Brenner, H., Buring, J.E., Chang-Claude, J., Chanock, S., Chen, J., Chenevix-Trench, G., Collee, J.M., Couch, F.J., Couper, D., Coviello, A.D., Cox, A, Czene, K., D'Adamo, P., Smith, G., Vivo, I. De, Demerath, E.W., Dennis, J., Devilee, P., Dieffenbach, A.K., Dunning, A.M., Eiriksdottir, G., Eriksson, J.G., Fasching, P.A., Ferrucci, L., Flesch-Janys, D., Flyger, H., Foroud, T., Franke, L., Garcia, M.E., Garcia-Closas, M., Geller, F., Geus, E.E. de, Giles, G.G., Gudbjartsson, D.F., Gudnason, V., Guenel, P., Guo, S., Hall, P., Hamann, U., Haring, R., Hartman, C.A., Heath, A.C., Hofman, A., Hooning, M.J., Hopper, J.L., Hu, F.B., Hunter, D.J., Karasik, D., Kiel, D.P., and et al.

Abstract

Contains fulltext : 136472.pdf (publisher's version ) (Closed access), Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 x 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and gamma-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.

Published
2014

74. Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche

Author

Perry, J.R.B. (John), Day, F.R. (Felix), Elks, C.E. (Cathy), Sulem, P. (Patrick), Thompson, D. (Deborah), Ferreira, T. (Teresa), He, C. (Chunyan), Chasman, D.I. (Daniel), Esko, T. (Tõnu), Thorleifsson, G. (Gudmar), Albrecht, E. (Eva), Ang, W.Q. (Wei), Corre, T. (Tanguy), Cousminer, D.L. (Diana), Feenstra, B. (Bjarke), Franceschini, N. (Nora), Ganna, A. (Andrea), Johnson, A.D. (Andrew), Kjellqvist, S. (Sanela), Lunetta, K.L. (Kathryn), Mcmahon, G. (George), Nolte, I.M. (Ilja), Paternoster, L. (Lavinia), Porcu, E. (Eleonora), Smith, A.V. (Davey), Stolk, L. (Lisette), Teumer, A. (Alexander), Tsernikova, N. (Natalia), Tikkanen, E. (Emmi), Ulivi, S. (Shelia), Wagner, E.K. (Erin K.), Amin, N. (Najaf), Bierut, L.J. (Laura), Byrne, E.M. (Enda), Hottenga, J.J. (Jouke Jan), Koller, D.L. (Daniel), Mangino, M. (Massimo), Pers, T.H. (Tune), Yerges-Armstrong, L.M. (Laura), Zhao, J.H. (Jing Hua), Andrulis, I.L. (Irene), Anton-Culver, H. (Hoda), Atsma, F. (Femke), Bandinelli, S. (Stefania), Beckmann, M.W. (Matthias), Benítez, J. (Javier), Blomqvist, C. (Carl), Bojesen, S.E. (Stig), Bolla, M.K. (Manjeet), Bonnani, B. (Bernardo), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Buring, J.E. (Julie), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen), Chen, J. (Jinhui), Chenevix-Trench, G. (Georgia), Collée, J.M. (Margriet), Couch, F.J. (Fergus), Couper, D.J. (David), Coviello, A.D. (Andrea), Cox, A. (Angela), Czene, K. (Kamila), Adamo, P. (Pio) d', Vivo, I. (Immaculata) de, Demerath, E.W. (Ellen), Dennis, J. (Joe), Devilee, P. (Peter), Dieffenbach, A.K. (Aida Karina), Dunning, A.M. (Alison), Eiriksdottir, G. (Gudny), Hagen, K. (Knut), Fasching, P.A. (Peter), Ferrucci, L. (Luigi), Flesch-Janys, D. (Dieter), Flyger, H. (Henrik), Foroud, T. (Tatiana), Franke, L. (Lude), Garcia, M. (Melissa), García-Closas, M. (Montserrat), Geller, F. (Frank), Geus, E.J.C. (Eco) de, Giles, G.G. (Graham), Gudbjartsson, D.F. (Daniel), Gudnason, V. (Vilmundur), Guénel, P. (Pascal), Guo, S. (Suiqun), Hall, P. (Per), Hamann, U. (Ute), Haring, R. (Robin), Hartman, C.A. (Catharina), Heath, A.C. (Andrew), Hofman, A. (Albert), Hooning, M.J. (Maartje), Hopper, J.L. (John), Hu, F.B. (Frank), Hunter, D. (David), Karasik, D. (David), Kiel, D.P. (Douglas P.), Knight, J.A. (Julia), Kosma, V-M. (Veli-Matti), Kutalik, Z. (Zoltán), Lai, S. (Sandra), Lambrechts, D. (Diether), Lindblom, A. (Annika), Mägi, R. (Reedik), Magnusson, P.K. (Patrik), Mannermaa, A. (Arto), Martin, N.G. (Nicholas), Masson, G. (Gisli), McArdle, P.F. (Patrick), McArdle, W.L. (Wendy), Melbye, M. (Mads), Michailidou, K. (Kyriaki), Mihailov, E. (Evelin), Milani, L. (Lili), Milne, R.L. (Roger L), Nevanlinna, H. (Heli), Neven, P. (Patrick), Nohr, C. (Christian), Oldehinkel, A.J. (Albertine), Oostra, B.A. (Ben), Palotie, A. (Aarno), Peacock, M. (Munro), Pedersen, N.L. (Nancy L.), Peterlongo, P. (Paolo), Peto, J. (Julian), Pharoah, P.D.P. (Paul), Postma, D.S. (Dirkje), Pouta, A. (Anneli), Pykäs, K. (Katri), Radice, P. (Paolo), Ring, S.M. (Susan), Rivadeneira Ramirez, F. (Fernando), Robino, A. (Antonietta), Rose, L.M. (Lynda), Rudolph, A. (Anja), Salomaa, V. (Veikko), Sanna, S. (Serena), Schlessinger, D. (David), Schmidt, M.K. (Marjanka), Southey, M.C. (Mellissa C.), Sovio, U. (Ulla), Stampfer, M.J. (Meir J.), Stöckl, D. (Doris), Storniolo, A.M. (Anna M.), Timpson, N.J. (Nicholas), Tyrer, J.P. (Jonathan), Visser, J.A. (Jenny), Vollenweider, P. (Peter), Völzke, H. (Henry), Waeber, G. (Gérard), Waldenberger, M. (Melanie), Wallaschofski, H. (Henri), Wang, Q. (Qing), Willemsen, G.A.H.M. (Gonneke), Winqvist, R. (Robert), Wolffenbuttel, B.H.R. (Bruce H. R.), Wright, M.J. (Margaret), Boomsma, D.I. (Dorret), Econs, M.J. (Michael), Khaw, K.T., Loos, R.J.F. (Ruth), McCarthy, M.I. (Mark), Montgomery, G.W. (Grant), Rice, J.P. (John), Streeten, E.A. (Elizabeth), Thorsteinsdottir, U. (Unnur), Duijn, C.M. (Cornelia) van, Alizadeh, B.Z. (Behrooz), Bergmann, S.M. (Sven), Boerwinkle, E.A. (Eric), Boyd, H.A. (Heather), Crisponi, L. (Laura), Gasparini, P. (Paolo), Gieger, C. (Christian), Harris, T.B. (Tamara), Ingelsson, E. (Erik), Jarvelin, M.-R. (Marjo-Riitta), Kraft, P. (Peter), Lawlor, D.A. (Debbie), Metspalu, A. (Andres), Pennell, C.E. (Craig), Ridker, P.M. (Paul), Snieder, H. (Harold), Sørensen, T.I.A., Spector, T.D. (Timothy), Strachan, D.P. (David P.), Uitterlinden, A.G. (André), Wareham, N.J. (Nick), Widen, E. (Elisabeth), Zygmunt, M. (Marek), Murray, A. (Anna), Easton, D.F. (Douglas), Zwart, J-A. (John-Anker), Murabito, J. (Joanne), Ong, K.K. (Ken K.), Perry, J.R.B. (John), Day, F.R. (Felix), Elks, C.E. (Cathy), Sulem, P. (Patrick), Thompson, D. (Deborah), Ferreira, T. (Teresa), He, C. (Chunyan), Chasman, D.I. (Daniel), Esko, T. (Tõnu), Thorleifsson, G. (Gudmar), Albrecht, E. (Eva), Ang, W.Q. (Wei), Corre, T. (Tanguy), Cousminer, D.L. (Diana), Feenstra, B. (Bjarke), Franceschini, N. (Nora), Ganna, A. (Andrea), Johnson, A.D. (Andrew), Kjellqvist, S. (Sanela), Lunetta, K.L. (Kathryn), Mcmahon, G. (George), Nolte, I.M. (Ilja), Paternoster, L. (Lavinia), Porcu, E. (Eleonora), Smith, A.V. (Davey), Stolk, L. (Lisette), Teumer, A. (Alexander), Tsernikova, N. (Natalia), Tikkanen, E. (Emmi), Ulivi, S. (Shelia), Wagner, E.K. (Erin K.), Amin, N. (Najaf), Bierut, L.J. (Laura), Byrne, E.M. (Enda), Hottenga, J.J. (Jouke Jan), Koller, D.L. (Daniel), Mangino, M. (Massimo), Pers, T.H. (Tune), Yerges-Armstrong, L.M. (Laura), Zhao, J.H. (Jing Hua), Andrulis, I.L. (Irene), Anton-Culver, H. (Hoda), Atsma, F. (Femke), Bandinelli, S. (Stefania), Beckmann, M.W. (Matthias), Benítez, J. (Javier), Blomqvist, C. (Carl), Bojesen, S.E. (Stig), Bolla, M.K. (Manjeet), Bonnani, B. (Bernardo), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Buring, J.E. (Julie), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen), Chen, J. (Jinhui), Chenevix-Trench, G. (Georgia), Collée, J.M. (Margriet), Couch, F.J. (Fergus), Couper, D.J. (David), Coviello, A.D. (Andrea), Cox, A. (Angela), Czene, K. (Kamila), Adamo, P. (Pio) d', Vivo, I. (Immaculata) de, Demerath, E.W. (Ellen), Dennis, J. (Joe), Devilee, P. (Peter), Dieffenbach, A.K. (Aida Karina), Dunning, A.M. (Alison), Eiriksdottir, G. (Gudny), Hagen, K. (Knut), Fasching, P.A. (Peter), Ferrucci, L. (Luigi), Flesch-Janys, D. (Dieter), Flyger, H. (Henrik), Foroud, T. (Tatiana), Franke, L. (Lude), Garcia, M. (Melissa), García-Closas, M. (Montserrat), Geller, F. (Frank), Geus, E.J.C. (Eco) de, Giles, G.G. (Graham), Gudbjartsson, D.F. (Daniel), Gudnason, V. (Vilmundur), Guénel, P. (Pascal), Guo, S. (Suiqun), Hall, P. (Per), Hamann, U. (Ute), Haring, R. (Robin), Hartman, C.A. (Catharina), Heath, A.C. (Andrew), Hofman, A. (Albert), Hooning, M.J. (Maartje), Hopper, J.L. (John), Hu, F.B. (Frank), Hunter, D. (David), Karasik, D. (David), Kiel, D.P. (Douglas P.), Knight, J.A. (Julia), Kosma, V-M. (Veli-Matti), Kutalik, Z. (Zoltán), Lai, S. (Sandra), Lambrechts, D. (Diether), Lindblom, A. (Annika), Mägi, R. (Reedik), Magnusson, P.K. (Patrik), Mannermaa, A. (Arto), Martin, N.G. (Nicholas), Masson, G. (Gisli), McArdle, P.F. (Patrick), McArdle, W.L. (Wendy), Melbye, M. (Mads), Michailidou, K. (Kyriaki), Mihailov, E. (Evelin), Milani, L. (Lili), Milne, R.L. (Roger L), Nevanlinna, H. (Heli), Neven, P. (Patrick), Nohr, C. (Christian), Oldehinkel, A.J. (Albertine), Oostra, B.A. (Ben), Palotie, A. (Aarno), Peacock, M. (Munro), Pedersen, N.L. (Nancy L.), Peterlongo, P. (Paolo), Peto, J. (Julian), Pharoah, P.D.P. (Paul), Postma, D.S. (Dirkje), Pouta, A. (Anneli), Pykäs, K. (Katri), Radice, P. (Paolo), Ring, S.M. (Susan), Rivadeneira Ramirez, F. (Fernando), Robino, A. (Antonietta), Rose, L.M. (Lynda), Rudolph, A. (Anja), Salomaa, V. (Veikko), Sanna, S. (Serena), Schlessinger, D. (David), Schmidt, M.K. (Marjanka), Southey, M.C. (Mellissa C.), Sovio, U. (Ulla), Stampfer, M.J. (Meir J.), Stöckl, D. (Doris), Storniolo, A.M. (Anna M.), Timpson, N.J. (Nicholas), Tyrer, J.P. (Jonathan), Visser, J.A. (Jenny), Vollenweider, P. (Peter), Völzke, H. (Henry), Waeber, G. (Gérard), Waldenberger, M. (Melanie), Wallaschofski, H. (Henri), Wang, Q. (Qing), Willemsen, G.A.H.M. (Gonneke), Winqvist, R. (Robert), Wolffenbuttel, B.H.R. (Bruce H. R.), Wright, M.J. (Margaret), Boomsma, D.I. (Dorret), Econs, M.J. (Michael), Khaw, K.T., Loos, R.J.F. (Ruth), McCarthy, M.I. (Mark), Montgomery, G.W. (Grant), Rice, J.P. (John), Streeten, E.A. (Elizabeth), Thorsteinsdottir, U. (Unnur), Duijn, C.M. (Cornelia) van, Alizadeh, B.Z. (Behrooz), Bergmann, S.M. (Sven), Boerwinkle, E.A. (Eric), Boyd, H.A. (Heather), Crisponi, L. (Laura), Gasparini, P. (Paolo), Gieger, C. (Christian), Harris, T.B. (Tamara), Ingelsson, E. (Erik), Jarvelin, M.-R. (Marjo-Riitta), Kraft, P. (Peter), Lawlor, D.A. (Debbie), Metspalu, A. (Andres), Pennell, C.E. (Craig), Ridker, P.M. (Paul), Snieder, H. (Harold), Sørensen, T.I.A., Spector, T.D. (Timothy), Strachan, D.P. (David P.), Uitterlinden, A.G. (André), Wareham, N.J. (Nick), Widen, E. (Elisabeth), Zygmunt, M. (Marek), Murray, A. (Anna), Easton, D.F. (Douglas), Zwart, J-A. (John-Anker), Murabito, J. (Joanne), and Ong, K.K. (Ken K.)

Abstract

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10-8) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarc

Published
2014
Full Text
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78. Verdronken dekzandlandschap in Flevoland

Author

Makaske, B., Kooistra, M.J., Haring, R., and van Smeerdijk, D.G.

Subjects
geology, bodemtypen, geologie, geomorfologie, bodemvorming, holocene, netherlands, soil types, geomorphology, holoceen, flevoland, soil formation, nederland
Abstract

Dit artikel gaat over landschappelijke veranderingen in Zuidelijk Flevoland in het midden Holoceen

Published
2001

79. p-i-n junction quantum dot saturable absorber mirror: electrical control of ultrafast dynamics

Author

Zolotovskaya, Svetlana, Butkus, M., Haring, R., Able, A., Kaenders, W., Krestnikov, I. L., Livshits, D. A., Rafailov, E. U., Zolotovskaya, Svetlana, Butkus, M., Haring, R., Able, A., Kaenders, W., Krestnikov, I. L., Livshits, D. A., and Rafailov, E. U.

Abstract

We report on nonlinear optical properties of a p-i-n junction quantum dot saturable absorber based on InGaAs/GaAs. Absorption recovery dynamics and nonlinear reflectivity are investigated for different reverse bias and pump power conditions. A decrease in absorption recovery time of nearly two orders of magnitude is demonstrated by applying a voltage between 0 and −20 V. The saturable absorber modulation depth and saturation fluence are found to be independent from the applied reverse bias.

Published
2012

80. A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple loci implicated in s

Author

Coviello, A.D. (Andrea), Haring, R. (Robin), Wellons, M. (Melissa), Vaidya, D. (Dhananjay), Lehtimäki, T. (Terho), Keildson, S. (Sarah), Lunetta, K.L. (Kathryn), He, C. (Chunyan), Fornage, M. (Myriam), Lagou, V. (Vasiliki), Mangino, M. (Massimo), Onland-Moret, N.C. (Charlotte), Chen, B.H. (Brian), Eriksson, J. (Joel), Garcia, M. (Melissa), Liu, Y. (YongMei), Koster, A. (Annemarie), Lohman, K. (Kurt), Lyytikäinen, L.-P. (Leo-Pekka), Petersen, A.K., Prescott, C.A.J., Stolk, L. (Lisette), Vandenput, L. (Liesbeth), Wood, A.R. (Andrew), Zhuang, W.V., Ruokonen, A. (Aimo), Hartikainen, A.L., Pouta, A. (Anneli), Bandinelli, S. (Stefania), Biffar, R. (Reiner), Brabant, G. (Georg), Cox, D.G. (David), Cummings, S., Ferrucci, L. (Luigi), Gunter, M.J. (Marc J.), Hankinson, S.E. (Susan), Martikainen, H. (Hannu), Hofman, A. (Albert), Homuth, G. (Georg), Illig, T. (Thomas), Jansson, J.O., Johnson, A.D. (Andrew), Karasik, D. (David), Karlsson, M. (Magnus), Kettunen, J. (Johannes), Kiel, D.P. (Douglas), Kraft, P. (Peter), Ljunggren, O. (Östen), Lorentzon, M. (Mattias), Maggio, M. (Marcello), Markus, M.R.P. (Marcello R. P.), Mellström, D. (Dan), Miljkovic, I. (Iva), Mirel, D. (Daniel), Nelson, S. (Sarah), Morin Papunen, L. (Laure), Peeters, P.H.M., Prokopenko, I. (Inga), Raffel, L.J. (Leslie), Reincke, M. (Martin), Reiner, A.P. (Alex), Rexrode, K. (Kathryn), Rivadeneira Ramirez, F. (Fernando), Schwartz, S.M. (Stephen), Siscovick, D.S. (David), Soranzo, N. (Nicole), Stöckl, D. (Doris), Tworoger, S. (Shelley), Uitterlinden, A.G. (André), Gils, C.H. (Carla) van, Vasan, R.S. (Ramachandran Srini), Wichmann, H.E. (Erich), Zhai, G. (Guangju), Bhasin, S. (Shalender), Bidlingmaier, M. (Martin), Chanock, S.J. (Stephen), Vivo, I. (Immaculata) de, Harris, T.B. (Tamara), Hunter, D. (David), Kähönen, M. (Mika), Ouyang, P. (Pamela), Spector, T.D. (Timothy), Schouw, Y.T. (Yvonne) van der, Viikari, J. (Jorma), Wallaschofski, H. (Henri), McCarthy, M.I. (Mark), Frayling, T.M. (Timothy), Murray, J.C. (Jeffrey), Franks, S. (Steve), Jarvelin, M.-R. (Marjo-Riitta), Jong, F.A. (Floris) de, Raitakari, O. (Olli), Teumer, A. (Alexander), Ohlsson, C. (Claes), Murabito, J. (Joanne), Perry, J.R.B. (John), Coviello, A.D. (Andrea), Haring, R. (Robin), Wellons, M. (Melissa), Vaidya, D. (Dhananjay), Lehtimäki, T. (Terho), Keildson, S. (Sarah), Lunetta, K.L. (Kathryn), He, C. (Chunyan), Fornage, M. (Myriam), Lagou, V. (Vasiliki), Mangino, M. (Massimo), Onland-Moret, N.C. (Charlotte), Chen, B.H. (Brian), Eriksson, J. (Joel), Garcia, M. (Melissa), Liu, Y. (YongMei), Koster, A. (Annemarie), Lohman, K. (Kurt), Lyytikäinen, L.-P. (Leo-Pekka), Petersen, A.K., Prescott, C.A.J., Stolk, L. (Lisette), Vandenput, L. (Liesbeth), Wood, A.R. (Andrew), Zhuang, W.V., Ruokonen, A. (Aimo), Hartikainen, A.L., Pouta, A. (Anneli), Bandinelli, S. (Stefania), Biffar, R. (Reiner), Brabant, G. (Georg), Cox, D.G. (David), Cummings, S., Ferrucci, L. (Luigi), Gunter, M.J. (Marc J.), Hankinson, S.E. (Susan), Martikainen, H. (Hannu), Hofman, A. (Albert), Homuth, G. (Georg), Illig, T. (Thomas), Jansson, J.O., Johnson, A.D. (Andrew), Karasik, D. (David), Karlsson, M. (Magnus), Kettunen, J. (Johannes), Kiel, D.P. (Douglas), Kraft, P. (Peter), Ljunggren, O. (Östen), Lorentzon, M. (Mattias), Maggio, M. (Marcello), Markus, M.R.P. (Marcello R. P.), Mellström, D. (Dan), Miljkovic, I. (Iva), Mirel, D. (Daniel), Nelson, S. (Sarah), Morin Papunen, L. (Laure), Peeters, P.H.M., Prokopenko, I. (Inga), Raffel, L.J. (Leslie), Reincke, M. (Martin), Reiner, A.P. (Alex), Rexrode, K. (Kathryn), Rivadeneira Ramirez, F. (Fernando), Schwartz, S.M. (Stephen), Siscovick, D.S. (David), Soranzo, N. (Nicole), Stöckl, D. (Doris), Tworoger, S. (Shelley), Uitterlinden, A.G. (André), Gils, C.H. (Carla) van, Vasan, R.S. (Ramachandran Srini), Wichmann, H.E. (Erich), Zhai, G. (Guangju), Bhasin, S. (Shalender), Bidlingmaier, M. (Martin), Chanock, S.J. (Stephen), Vivo, I. (Immaculata) de, Harris, T.B. (Tamara), Hunter, D. (David), Kähönen, M. (Mika), Ouyang, P. (Pamela), Spector, T.D. (Timothy), Schouw, Y.T. (Yvonne) van der, Viikari, J. (Jorma), Wallaschofski, H. (Henri), McCarthy, M.I. (Mark), Frayling, T.M. (Timothy), Murray, J.C. (Jeffrey), Franks, S. (Steve), Jarvelin, M.-R. (Marjo-Riitta), Jong, F.A. (Floris) de, Raitakari, O. (Olli), Teumer, A. (Alexander), Ohlsson, C. (Claes), Murabito, J. (Joanne), and Perry, J.R.B. (John)

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 with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs) associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG, PRMT6, GCKR, ZBTB10, JMJD1C, SLCO1B1, NR2F2, ZNF652, TDGF3, LHCGR, BAIAP2L1, and UGT2B15. These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only. Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion of variance explained at the locus. Using an independent study of 1,129 individuals, all SNPs identified in the overall or sex-differentiated or conditional analyses explained ~15.6% and ~8.4% of the genetic variation of SHBG concentrations in men and women, respectively. The evidence for sex-differentiated effects and allelic heterogeneity highlight the importance of considering these features when estimating complex trait variance.

Published
2012
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81. A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple loci implicated in sex steroid hormone regulation

Author

Coviello, AD, Haring, R, Wellons, M, Vaidya, D, Lehtimäki, T, Keildson, S, Lunetta, KL, He, C, Fornage, M, Lagou, V, Mangino, M, Onland-Moret, NC, Chen, B, Eriksson, J, Garcia, M, Liu, YM, Koster, A, Lohman, K, Lyytikäinen, LP, Petersen, AK, Prescott, J, Stolk, L, Vandenput, L, Wood, AR, Zhuang, WV, Ruokonen, A, Hartikainen, AL, Pouta, A, Bandinelli, S, Biffar, R, Brabant, G, Cox, DG, Chen, Y, Cummings, S, Ferrucci, L, Gunter, MJ, Hankinson, SE, Martikainen, H, Hofman, A, Homuth, G, Illig, T, Jansson, JO, Johnson, AD, Karasik, D, Karlsson, M, Kettunen, J, Kiel, DP, Kraft, P, Liu, J, Ljunggren, O, Lorentzon, M, Maggio, M, Markus, MRP, Mellström, D, Miljkovic, I, Mirel, D, Nelson, S, Morin Papunen, L, Peeters, PHM, Prokopenko, I, Raffel, L, Reincke, M, Reiner, AP, Rexrode, K, Rivadeneira, F, Schwartz, SM, Siscovick, D, Soranzo, N, Stöckl, D, Tworoger, S, Uitterlinden, AG, van Gils, CH, Vasan, RS, Wichmann, HE, Zhai, G, Bhasin, S, Bidlingmaier, M, Chanock, SJ, de Vivo, I, Harris, TB, Hunter, DJ, Kähönen, M, Liu, S, Ouyang, P, Spector, TD, van der Schouw, YT, Viikari, J, Wallaschofski, H, McCarthy, MI, Frayling, TM, Murray, A, Franks, S, Järvelin, MR, de Jong, FH, Raitakari, O, Teumer, A, Ohlsson, C, Murabito, JM, Perry, JRB, Coviello, AD, Haring, R, Wellons, M, Vaidya, D, Lehtimäki, T, Keildson, S, Lunetta, KL, He, C, Fornage, M, Lagou, V, Mangino, M, Onland-Moret, NC, Chen, B, Eriksson, J, Garcia, M, Liu, YM, Koster, A, Lohman, K, Lyytikäinen, LP, Petersen, AK, Prescott, J, Stolk, L, Vandenput, L, Wood, AR, Zhuang, WV, Ruokonen, A, Hartikainen, AL, Pouta, A, Bandinelli, S, Biffar, R, Brabant, G, Cox, DG, Chen, Y, Cummings, S, Ferrucci, L, Gunter, MJ, Hankinson, SE, Martikainen, H, Hofman, A, Homuth, G, Illig, T, Jansson, JO, Johnson, AD, Karasik, D, Karlsson, M, Kettunen, J, Kiel, DP, Kraft, P, Liu, J, Ljunggren, O, Lorentzon, M, Maggio, M, Markus, MRP, Mellström, D, Miljkovic, I, Mirel, D, Nelson, S, Morin Papunen, L, Peeters, PHM, Prokopenko, I, Raffel, L, Reincke, M, Reiner, AP, Rexrode, K, Rivadeneira, F, Schwartz, SM, Siscovick, D, Soranzo, N, Stöckl, D, Tworoger, S, Uitterlinden, AG, van Gils, CH, Vasan, RS, Wichmann, HE, Zhai, G, Bhasin, S, Bidlingmaier, M, Chanock, SJ, de Vivo, I, Harris, TB, Hunter, DJ, Kähönen, M, Liu, S, Ouyang, P, Spector, TD, van der Schouw, YT, Viikari, J, Wallaschofski, H, McCarthy, MI, Frayling, TM, Murray, A, Franks, S, Järvelin, MR, de Jong, FH, Raitakari, O, Teumer, A, Ohlsson, C, Murabito, JM, and Perry, JRB

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 with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs) associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, 17p13.1, p = 1.8×10-106), PRMT6 (rs17496332, 1p13.3, p = 1.4×10-11), GCKR (rs780093, 2p23.3, p = 2.2×10-16), ZBTB10 (rs440837, 8q21.13, p = 3.4×10-09), JMJD1C (rs7910927, 10q21.3, p = 6.1×10-35), SLCO1B1 (rs4149056, 12p12.1, p = 1.9×10-08), NR2F2 (rs8023580, 15q26.2, p = 8.3×10-12), ZNF652 (rs2411984, 17q21.32, p = 3.5×10-14), TDGF3 (rs1573036, Xq22.3, p = 4.1×10-14), LHCGR (rs10454142, 2p16.3, p = 1.3×10-07), BAIAP2L1 (rs3779195, 7q21.3, p = 2.7×10-08), and UGT2B15 (rs293428, 4q13.2, p = 5.5×10-06). These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only (men p = 2.5×10-08, women p = 0.66, heterogeneity p = 0.003). Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion of variance explained at the locus. Using an independen

Published
2012

83. Cohort profile: The study of health in Pomerania

Author

Völzke, H. (Henry), Alte, D. (Dietrich), Schmidt, C.O. (Carsten Oliver), Radke, D. (Dörte), Lorbeer, R. (Roberto), Friedrich, N. (Nele), Aumann, N. (Nicole), Lau, K. (Katharina), Piontek, M. (Michael), Born, G. (Gabriele), Havemann, C. (Christoph), Ittermann, T. (Till), Schipf, S. (Sabine), Haring, R. (Robin), Baumeister, S.E. (Sebastian), Wallaschofski, H. (Henri), Nauck, M. (Matthias), Frick, S. (Stephanie), Arnold, A. (Andreas), Jünger, M. (Michael), Mayerle, J. (Julia), Kraft, M. (Matthias), Lerch, M.M. (Markus), Dörr, M. (Marcus), Reffelmann, T. (Thorsten), Empen, K. (Klaus), Felix, S.B. (Stephan), Obst, A. (Anne), Koch, B. (Beate), Gläser, S. (Sven), Ewert, R. (Ralf), Fietze, I. (Ingo), Penzel, T. (Thomas), Dören, M. (Martina), Rathmann, W. (Wolfgang), Haerting, J. (Johannes), Hannemann, M. (Mario), Röpcke, J. (Jürgen), Schminke, U. (Ulf), Jürgens, C. (Clemens), Tost, F. (Frank), Rettig, R. (Rainer), Kors, J.A. (Jan), Ungerer, S. (Saskia), Hegenscheid, K. (Katrin), Kühn, J.-P., Hosten, N. (Norbert), Puls, R. (Ralf), Henke, J. (Jörg), Gloger, O. (Oliver), Teumer, A. (Alexander), Homuth, G. (Georg), Völker, U. (Uwe), Schwahn, C. (Christian), Holtfreter, B. (Birte), Polzer, I. (Ines), Kohlmann, T. (Thomas), Grabe, H.J. (Hans Jörgen), Rosskopf, D. (Dieter), Kroemer, H.K. (Heyo), Kocher, T. (Thomas), Biffar, R. (Reiner), John, U. (Ulrich), Hoffmann, W. (Wolfgang), Völzke, H. (Henry), Alte, D. (Dietrich), Schmidt, C.O. (Carsten Oliver), Radke, D. (Dörte), Lorbeer, R. (Roberto), Friedrich, N. (Nele), Aumann, N. (Nicole), Lau, K. (Katharina), Piontek, M. (Michael), Born, G. (Gabriele), Havemann, C. (Christoph), Ittermann, T. (Till), Schipf, S. (Sabine), Haring, R. (Robin), Baumeister, S.E. (Sebastian), Wallaschofski, H. (Henri), Nauck, M. (Matthias), Frick, S. (Stephanie), Arnold, A. (Andreas), Jünger, M. (Michael), Mayerle, J. (Julia), Kraft, M. (Matthias), Lerch, M.M. (Markus), Dörr, M. (Marcus), Reffelmann, T. (Thorsten), Empen, K. (Klaus), Felix, S.B. (Stephan), Obst, A. (Anne), Koch, B. (Beate), Gläser, S. (Sven), Ewert, R. (Ralf), Fietze, I. (Ingo), Penzel, T. (Thomas), Dören, M. (Martina), Rathmann, W. (Wolfgang), Haerting, J. (Johannes), Hannemann, M. (Mario), Röpcke, J. (Jürgen), Schminke, U. (Ulf), Jürgens, C. (Clemens), Tost, F. (Frank), Rettig, R. (Rainer), Kors, J.A. (Jan), Ungerer, S. (Saskia), Hegenscheid, K. (Katrin), Kühn, J.-P., Hosten, N. (Norbert), Puls, R. (Ralf), Henke, J. (Jörg), Gloger, O. (Oliver), Teumer, A. (Alexander), Homuth, G. (Georg), Völker, U. (Uwe), Schwahn, C. (Christian), Holtfreter, B. (Birte), Polzer, I. (Ines), Kohlmann, T. (Thomas), Grabe, H.J. (Hans Jörgen), Rosskopf, D. (Dieter), Kroemer, H.K. (Heyo), Kocher, T. (Thomas), Biffar, R. (Reiner), John, U. (Ulrich), and Hoffmann, W. (Wolfgang)

Published
2011
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84. Genetic determinants of serum testosterone concentrations in men

Author

Ohlsson, C. (Claes), Wallaschofski, H. (Henri), Lunetta, K.L. (Kathryn), Stolk, L. (Lisette), Perry, J.R.B. (John), Koster, A. (Annemarie), Petersen, A.K., Eriksson, J. (Joel), Lehtimäki, T. (Terho), Huhtaniemi, I.T. (Ilpo), Hammond, G.L. (Geoffrey), Maggio, M. (Marcello), Coviello, A.D. (Andrea), Ferrucci, L. (Luigi), Heier, M. (Margit), Hofman, A. (Albert), Holliday, K.L. (Kate), Jansson, J.O., Kähönen, M. (Mika), Karasik, D. (David), Karlsson, M.K. (Magnus), Kiel, D.P. (Douglas), Liu, Y. (YongMei), Ljunggren, Ö., Lorentzon, M. (Mattias), Lyytikäinen, L.-P. (Leo-Pekka), Meitinger, T. (Thomas), Mellström, D. (Dan), Melzer, D. (David), Miljkovic, I. (Iva), Nauck, M. (Matthias), Nilsson, M. (Maria), Penninx, B.W.J.H. (Brenda), Pye, S.R. (Stephen), Vasan, R.S. (Ramachandran Srini), Reincke, M. (Martin), Rivadeneira Ramirez, F. (Fernando), Tajar, A. (Abdelouahid), Teumer, A. (Alexander), Uitterlinden, A.G. (André), Ulloor, J. (Jagadish), Viikari, J. (Jorma), Völker, U. (Uwe), Völzke, H. (Henry), Wichmann, H.E. (Heinz Erich), Wu, T.-S., Zhuang, W.V., Ziv, E. (Elad), Raitakari, O. (Olli), Bidlingmaier, M. (Martin), Harris, T.B. (Tamara), Murray, A. (Anna), Jong, F.H. (Frank) de, Murabito, J. (Joanne), Bhasin, S. (Shalender), Vandenput, L. (Liesbeth), Haring, R. (Robin), Ohlsson, C. (Claes), Wallaschofski, H. (Henri), Lunetta, K.L. (Kathryn), Stolk, L. (Lisette), Perry, J.R.B. (John), Koster, A. (Annemarie), Petersen, A.K., Eriksson, J. (Joel), Lehtimäki, T. (Terho), Huhtaniemi, I.T. (Ilpo), Hammond, G.L. (Geoffrey), Maggio, M. (Marcello), Coviello, A.D. (Andrea), Ferrucci, L. (Luigi), Heier, M. (Margit), Hofman, A. (Albert), Holliday, K.L. (Kate), Jansson, J.O., Kähönen, M. (Mika), Karasik, D. (David), Karlsson, M.K. (Magnus), Kiel, D.P. (Douglas), Liu, Y. (YongMei), Ljunggren, Ö., Lorentzon, M. (Mattias), Lyytikäinen, L.-P. (Leo-Pekka), Meitinger, T. (Thomas), Mellström, D. (Dan), Melzer, D. (David), Miljkovic, I. (Iva), Nauck, M. (Matthias), Nilsson, M. (Maria), Penninx, B.W.J.H. (Brenda), Pye, S.R. (Stephen), Vasan, R.S. (Ramachandran Srini), Reincke, M. (Martin), Rivadeneira Ramirez, F. (Fernando), Tajar, A. (Abdelouahid), Teumer, A. (Alexander), Uitterlinden, A.G. (André), Ulloor, J. (Jagadish), Viikari, J. (Jorma), Völker, U. (Uwe), Völzke, H. (Henry), Wichmann, H.E. (Heinz Erich), Wu, T.-S., Zhuang, W.V., Ziv, E. (Elad), Raitakari, O. (Olli), Bidlingmaier, M. (Martin), Harris, T.B. (Tamara), Murray, A. (Anna), Jong, F.H. (Frank) de, Murabito, J. (Joanne), Bhasin, S. (Shalender), Vandenput, L. (Liesbeth), and Haring, R. (Robin)

Abstract

Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone's high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n = 871) and two de novo replication cohorts (n = 4,620) to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as <300 ng/dl. Two single-nucleotide polymorphisms at the sex hormone-binding globulin (SHBG) locus (17p13-p12) were identified as independently associated with serum testosterone concentration (rs12150660, p = 1.2×10-41and rs6258, p = 2.3×10-22). Subjects with ≥3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (p = 5.6×10-16). The rs6258 polymorphism in exon 4 of SHBG affected SHBG's affinity for binding testosterone and the measured free testosterone fraction (p<0.01). Genetic variants in the SHBG locus and on the X chromosome are associated with a substantial variation in testosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation.

Published
2011
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85. Eight common genetic variants associated with serum dheas levels suggest a key role in ageing mechanisms

Author

Zhai, G. (Guangju), Teumer, A. (Alexander), Stolk, L. (Lisette), Perry, J.R.B. (John), Vandenput, L. (Liesbeth), Coviello, A.D. (Andrea), Koster, A. (Annemarie), Bell, J.T. (Jordana), Bhasin, S. (Shalender), Eriksson, J. (Joel), Ernst, F.D.J. (Florian), Ferrucci, L. (Luigi), Frayling, T.M. (Timothy), Glass, D. (Daniel), Grundberg, E. (Elin), Haring, R. (Robin), HedmanÅ, A.K., Hofman, A. (Albert), Kiel, D.P. (Douglas), Kroemer, H.K. (Heyo), Liu, Y. (YongMei), Lunetta, K.L. (Kathryn), Maggio, M. (Marcello), Lorentzon, M. (Mattias), Mangino, M. (Massimo), Melzer, D. (David), Miljkovic, I. (Iva), Nica, A. (Alexandra), Penninx, B.W.J.H. (Brenda), Vasan, R.S. (Ramachandran Srini), Rivadeneira Ramirez, F. (Fernando), Small, K.S. (Kerrin), Soranzo, N. (Nicole), Uitterlinden, A.G. (André), Völzke, H. (Henry), Wilson, S.G. (Scott), Xi, L. (Li), Zhuang, W.V., Jong, F.H. (Frank) de, Harris, T.B. (Tamara), Murabito, J. (Joanne), Ohlsson, C. (Claes), Murray, A. (Anna), Spector, T.D. (Timothy), Wallaschofski, H. (Henri), Zhai, G. (Guangju), Teumer, A. (Alexander), Stolk, L. (Lisette), Perry, J.R.B. (John), Vandenput, L. (Liesbeth), Coviello, A.D. (Andrea), Koster, A. (Annemarie), Bell, J.T. (Jordana), Bhasin, S. (Shalender), Eriksson, J. (Joel), Ernst, F.D.J. (Florian), Ferrucci, L. (Luigi), Frayling, T.M. (Timothy), Glass, D. (Daniel), Grundberg, E. (Elin), Haring, R. (Robin), HedmanÅ, A.K., Hofman, A. (Albert), Kiel, D.P. (Douglas), Kroemer, H.K. (Heyo), Liu, Y. (YongMei), Lunetta, K.L. (Kathryn), Maggio, M. (Marcello), Lorentzon, M. (Mattias), Mangino, M. (Massimo), Melzer, D. (David), Miljkovic, I. (Iva), Nica, A. (Alexandra), Penninx, B.W.J.H. (Brenda), Vasan, R.S. (Ramachandran Srini), Rivadeneira Ramirez, F. (Fernando), Small, K.S. (Kerrin), Soranzo, N. (Nicole), Uitterlinden, A.G. (André), Völzke, H. (Henry), Wilson, S.G. (Scott), Xi, L. (Li), Zhuang, W.V., Jong, F.H. (Frank) de, Harris, T.B. (Tamara), Murabito, J. (Joanne), Ohlsson, C. (Claes), Murray, A. (Anna), Spector, T.D. (Timothy), and Wallaschofski, H. (Henri)

Abstract

Dehydroepiandrosterone sulphate (DHEAS) is the most abundant circulating steroid secreted by adrenal glands-yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15×10-36), SULT2A1 (rs2637125; p = 2.61×10-19), ARPC1A (rs740160; p = 1.56×10-16), TRIM4 (rs17277546; p = 4.50×10-11), BMF (rs7181230; p = 5.44×10-11), HHEX (rs2497306; p = 4.64×10-9), BCL2L11 (rs6738028; p = 1.72×10-8), and CYP2C9 (rs2185570; p = 2.29×10-8). These genes are associated with type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins. Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS

Published
2011
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86. Genetic determinants of serum testosterone concentrations in men

Author

Ohlsson, C, Wallaschofski, H, Lunetta, KL, Stolk, L, Perry, JRB, Koster, A, Petersen, AK, Eriksson, J, Lehtimäki, T, Huhtaniemi, IT, Hammond, GL, Maggio, M, Coviello, AD, Emas Study Group, Ferrucci, L, Heier, M, Hofman, A, Holliday, KL, Jansson, JO, Kähönen, M, Karasik, D, Karlsson, MK, Kiel, DP, Liu, Y, Ljunggren, O, Lorentzon, M, Lyytikäinen, LP, Meitinger, T, Mellström, D, Melzer, D, Miljkovic, I, Nauck, M, Nilsson, M, Penninx, B, Pye, SR, Vasan, RS, Reincke, M, Rivadeneira, F, Tajar, A, Teumer, A, Uitterlinden, AG, Ulloor, J, Viikari, J, Völker, U, Völzke, H, Wichmann, HE, Wu, TS, Zhuang, WV, Ziv, E, Wu, FCW, Raitakari, O, Eriksson, A, Bidlingmaier, M, Harris, TB, Murray, A, de Jong, FH, Murabito, JM, Bhasin, S, Vandenput, L, Haring, R, Ohlsson, C, Wallaschofski, H, Lunetta, KL, Stolk, L, Perry, JRB, Koster, A, Petersen, AK, Eriksson, J, Lehtimäki, T, Huhtaniemi, IT, Hammond, GL, Maggio, M, Coviello, AD, Emas Study Group, Ferrucci, L, Heier, M, Hofman, A, Holliday, KL, Jansson, JO, Kähönen, M, Karasik, D, Karlsson, MK, Kiel, DP, Liu, Y, Ljunggren, O, Lorentzon, M, Lyytikäinen, LP, Meitinger, T, Mellström, D, Melzer, D, Miljkovic, I, Nauck, M, Nilsson, M, Penninx, B, Pye, SR, Vasan, RS, Reincke, M, Rivadeneira, F, Tajar, A, Teumer, A, Uitterlinden, AG, Ulloor, J, Viikari, J, Völker, U, Völzke, H, Wichmann, HE, Wu, TS, Zhuang, WV, Ziv, E, Wu, FCW, Raitakari, O, Eriksson, A, Bidlingmaier, M, Harris, TB, Murray, A, de Jong, FH, Murabito, JM, Bhasin, S, Vandenput, L, and Haring, R

Abstract

Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone's high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n = 871) and two de novo replication cohorts (n = 4,620) to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as <300 ng/dl. Two single-nucleotide polymorphisms at the sex hormone-binding globulin (SHBG) locus (17p13-p12) were identified as independently associated with serum testosterone concentration (rs12150660, p = 1.2×10 -41 and rs6258, p = 2.3×10 -22). Subjects with ≥3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (p = 5.6×10 -16). The rs6258 polymorphism in exon 4 of SHBG affected SHBG's affinity for binding testosterone and the measured free testosterone fraction (p<0.01). Genetic variants in the SHBG locus and on the X chromosome are associated with a substantial variation in testosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation.

Published
2011

87. Eight Common Genetic Variants Associated with Serum DHEAS Levels Suggest a Key Role in Ageing Mechanisms

Author

Zhai, GJ, Teumer, A, Stolk, Lisette, Perry, JRB, Vandenput, L, Coviello, AD, Koster, A, Bell, JT, Bhasin, S, Eriksson, J, Eriksson, A, Ernst, F, Ferrucci, L, Frayling, TM, Glass, D, Grundberg, E, Haring, R, Hedman, AK, Hofman, Bert, Kiel, DP, Kroemer, HK, Liu, YM, Lunetta, KL, Maggio, M, Lorentzon, M, Mangino, M, Melzer, D, Miljkovic, I, Nica, A, Penninx, BWJH, Vasan, RS, Rivadeneira, Fernando, Small, KS, Soranzo, N, Uitterlinden, André, Volzke, H, Wilson, SG, Xi, L, Zhuang, WV, Harris, TB, Murabito, JM, Ohlsson, C, Murray, A, Jong, Frank, Spector, TD, Wallaschofski, H, Zhai, GJ, Teumer, A, Stolk, Lisette, Perry, JRB, Vandenput, L, Coviello, AD, Koster, A, Bell, JT, Bhasin, S, Eriksson, J, Eriksson, A, Ernst, F, Ferrucci, L, Frayling, TM, Glass, D, Grundberg, E, Haring, R, Hedman, AK, Hofman, Bert, Kiel, DP, Kroemer, HK, Liu, YM, Lunetta, KL, Maggio, M, Lorentzon, M, Mangino, M, Melzer, D, Miljkovic, I, Nica, A, Penninx, BWJH, Vasan, RS, Rivadeneira, Fernando, Small, KS, Soranzo, N, Uitterlinden, André, Volzke, H, Wilson, SG, Xi, L, Zhuang, WV, Harris, TB, Murabito, JM, Ohlsson, C, Murray, A, Jong, Frank, Spector, TD, and Wallaschofski, H

Abstract

Dehydroepiandrosterone sulphate (DHEAS) is the most abundant circulating steroid secreted by adrenal glands-yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15610(-36)), SULT2A1 (rs2637125; p = 2.61610(-19)), ARPC1A (rs740160; p = 1.56610(-16)), TRIM4 (rs17277546; p = 4.50610(-11)), BMF (rs7181230; p = 5.44610(-11)), HHEX (rs2497306; p = 4.64610(-9)), BCL2L11 ( rs6738028; p = 1.72610(-8)), and CYP2C9 (rs2185570; p = 2.29610(-8)). These genes are associated with type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins. Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS.

Published
2011

89. The association of serum testosterone levels and ventricular repolarization

Author

Noord, C. (Charlotte) van, Dörr, M. (Marcus), Sturkenboom, M.C.J.M. (Miriam), Straus, S.M.J.M. (Sabine), Reffelmann, T. (Thorsten), Felix, S.B. (Stephan), Hofman, A. (Albert), Kors, J.A. (Jan), Haring, R. (Robin), Jong, F.H. (Frank) de, Nauck, M. (Matthias), Uitterlinden, A.G. (André), Wallaschofski, H. (Henri), Witteman, J.C.M. (Jacqueline), Völzke, H. (Henry), Stricker, B.H.Ch. (Bruno), Noord, C. (Charlotte) van, Dörr, M. (Marcus), Sturkenboom, M.C.J.M. (Miriam), Straus, S.M.J.M. (Sabine), Reffelmann, T. (Thorsten), Felix, S.B. (Stephan), Hofman, A. (Albert), Kors, J.A. (Jan), Haring, R. (Robin), Jong, F.H. (Frank) de, Nauck, M. (Matthias), Uitterlinden, A.G. (André), Wallaschofski, H. (Henri), Witteman, J.C.M. (Jacqueline), Völzke, H. (Henry), and Stricker, B.H.Ch. (Bruno)

Abstract

It is assumed that testosterone is an important regulator of gender-related differences in ventricular repolarization. Therefore, our aim was to study whether serum levels of testosterone are associated with QTc, QT and RR interval variation. Setting: two independent population-based cohort studies. Participants: 445 male participants (≥ 55 years) from the Rotterdam study cohort and 1,428 male participants from the study of health in Pomerania (SHIP) with an electrocardiogram who were randomly sampled for assessment of serum testosterone at baseline, after exclusion of participants with testosterone altering drugs, QTc prolonging drugs or dig(it)oxin, left ventricular hypertrophy and left and right bundle branch block. Endpoints: length of the QTc, QT and RR intervals. Analysis: linear regression model, adjusted for the two individual studies and a pooled analysis of both studies. The pooled analysis of the Rotterdam study and SHIP showed that the QTc interval gradually decreased among the tertiles (P value for trend 0.024). The third tertile of serum testosterone was associated with a lower QTc interval compared to the first tertile [-3.4 ms (-6.5; -0.3)]. However, the third tertile of serum testosterone was not associated with a lower QT interval compared to the first tertile [-0.7 ms (-3.1; 1.8)]. The RR interval gradually increased among the tertiles (P value for trend 0.002) and the third tertile of serum testosterone showed an increased RR interval compared to the first tertile [33.5 ms (12.2; 54.8)]. In the pooled analysis of two population-based studies, serum testosterone levels were not associated with the QT interval, which could be due to a lack of power. Lower QTc intervals in men with higher serum testosterone levels could be due to the association of serum testosterone with prolongation of the RR interval.

Published
2010
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90. The association of serum testosterone levels and ventricular repolarization

Author

Noord, Charlotte, Dorr, M, Sturkenboom, MCJM, Straus, Sabine, Reffelmann, T, Felix, SB, Hofman, Bert, Kors, Jan, Haring, R, Jong, Frank, Nauck, M, Uitterlinden, André, Wallaschofski, H, Witteman, JCM, Volzke, H, Stricker, Bruno, Noord, Charlotte, Dorr, M, Sturkenboom, MCJM, Straus, Sabine, Reffelmann, T, Felix, SB, Hofman, Bert, Kors, Jan, Haring, R, Jong, Frank, Nauck, M, Uitterlinden, André, Wallaschofski, H, Witteman, JCM, Volzke, H, and Stricker, Bruno

Abstract

It is assumed that testosterone is an important regulator of gender-related differences in ventricular repolarization. Therefore, our aim was to study whether serum levels of testosterone are associated with QTc, QT and RR interval variation. Setting: two independent population-based cohort studies. Participants: 445 male participants (a parts per thousand yen55 years) from the Rotterdam study cohort and 1,428 male participants from the study of health in Pomerania (SHIP) with an electrocardiogram who were randomly sampled for assessment of serum testosterone at baseline, after exclusion of participants with testosterone altering drugs, QTc prolonging drugs or dig(it)oxin, left ventricular hypertrophy and left and right bundle branch block. Endpoints: length of the QTc, QT and RR intervals. Analysis: linear regression model, adjusted for the two individual studies and a pooled analysis of both studies. The pooled analysis of the Rotterdam study and SHIP showed that the QTc interval gradually decreased among the tertiles (P value for trend 0.024). The third tertile of serum testosterone was associated with a lower QTc interval compared to the first tertile [-3.4 ms (-6.5; -0.3)]. However, the third tertile of serum testosterone was not associated with a lower QT interval compared to the first tertile [-0.7 ms (-3.1; 1.8)]. The RR interval gradually increased among the tertiles (P value for trend 0.002) and the third tertile of serum testosterone showed an increased RR interval compared to the first tertile [33.5 ms (12.2; 54.8)]. In the pooled analysis of two population-based studies, serum testosterone levels were not associated with the QT interval, which could be due to a lack of power. Lower QTc intervals in men with higher serum testosterone levels could be due to the association of serum testosterone with prolongation of the RR interval.

Published
2010

91. Improving the resolution of cryopreserved X- and Y-sperm during DNA flow cytometric analysis with the addition of Percoll to quench the fluorescence of dead sperm

Author

Stap, J., Hoebe, R. A., Merton, J. S., Haring, R. M., Bakker, P. J., Aten, J. A., and Other departments

Subjects
endocrine system, urogenital system, reproductive and urinary physiology
Abstract

The most effective method to control the sex of offspring is by separating X- from Y-bearing sperm on the basis of their DNA content. Sperm can be stained with Hoechst 33342 and efficiently sexed using a flow cytometer/cell sorter. However, applying this established assay to cryopreserved bovine sperm presents specific problems, such as broad fluorescence distributions without a distinct X- and Y-peak. Our results indicate that these problems are mainly caused by the large amount of dead sperm normally present in a thawed sperm population. We showed that Percoll quenches the fluorescence of chromatin stained with Hoechst 33342 and that this quenching can be applied to reduce the fluorescence of dead sperm. We used this finding to exclude the dead sperm from the sorting window and thus obtained narrower fluorescence distributions and sorted X- and Y-bearing sperm populations containing up to 85 to 92% viable sperm. The viability of the sorted sperm was monitored by propidium iodide exclusion

Published
1998

93. Design for low power and power management in IBM Blue Gene/Q

Author

Sugavanam, K., primary, Cher, C.-Y., additional, Gunnels, J. A., additional, Haring, R. A., additional, Heidelberger, P., additional, Jacobson, H. M., additional, McManus, M. K., additional, Paulsen, D. P., additional, Satterfield, D. L., additional, Sugawara, Y., additional, and Walkup, R., additional

Published
2013
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