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4. Screening for and Managing the Person with Frailty in Primary Care: ICFSR Consensus Guidelines

Author

Ruiz, J.G., Dent, E., Morley, John E., Merchant, R.A., Beilby, J., Beard, J., Tripathy, C., Sorin, M., Andrieu, S., Aprahamian, I., Arai, H., Aubertin-Leheudre, M., Bauer, J.M., Cesari, M., Chen, L.-K., Cruz-Jentoft, A.J., De Souto Barreto, P., Dong, B., Ferrucci, L., Fielding, R., Flicker, L., Lundy, J., Reginster, J.Y., Rodriguez-Mañas, L., Rolland, Y., Sanford, A.M., Sinclair, A.J., Viña, J., Waters, D.L., Won, C. Won, Woo, J., and Vellas, B.

Published
2020
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6. Lipidomic Risk Score to Enhance Cardiovascular Risk Stratification for Primary Prevention

Author

Wu, J, Giles, C, Dakic, A, Beyene, HB, Huynh, K, Wang, T, Meikle, T, Olshansky, G, Salim, A, Duong, T, Watts, GF, Hung, J, Hui, J, Cadby, G, Beilby, J, Blangero, J, Moses, EK, Shaw, JE, Magliano, DJ, Zhu, D, Yang, JY, Grieve, SM, Wilson, A, Chow, CK, Vernon, ST, Gray, MP, Figtree, GA, Carrington, MJ, Inouye, M, Marwick, TH, Meikle, PJ, Wu, J, Giles, C, Dakic, A, Beyene, HB, Huynh, K, Wang, T, Meikle, T, Olshansky, G, Salim, A, Duong, T, Watts, GF, Hung, J, Hui, J, Cadby, G, Beilby, J, Blangero, J, Moses, EK, Shaw, JE, Magliano, DJ, Zhu, D, Yang, JY, Grieve, SM, Wilson, A, Chow, CK, Vernon, ST, Gray, MP, Figtree, GA, Carrington, MJ, Inouye, M, Marwick, TH, and Meikle, PJ

Abstract

BACKGROUND: Accurate risk stratification is vital for primary prevention of cardiovascular disease (CVD). However, traditional tools such as the Framingham Risk Score (FRS) may underperform within the diverse intermediate-risk group, which includes individuals requiring distinct management strategies. OBJECTIVES: This study aimed to develop a lipidomic-enhanced risk score (LRS), specifically targeting risk prediction and reclassification within the intermediate group, benchmarked against the FRS. METHODS: The LRS was developed via a machine learning workflow using ridge regression on the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab; n = 10,339). It was externally validated with the Busselton Health Study (n = 4,492), and its predictive utility for coronary artery calcium scoring (CACS)-based outcomes was independently validated in the BioHEART cohort (n = 994). RESULTS: LRS significantly improved discrimination metrics for the intermediate-risk group in both AusDiab and Busselton Health Study cohorts (all P < 0.001), increasing the area under the curve for CVD events by 0.114 (95% CI: 0.1123-0.1157) and 0.077 (95% CI: 0.0755-0.0785), with a net reclassification improvement of 0.36 (95% CI: 0.21-0.51) and 0.33 (95% CI: 0.15-0.49), respectively. For CACS-based outcomes in BioHEART, LRS achieved a significant area under the curve improvement of 0.02 over the FRS (0.76 vs 0.74; P < 1.0 × 10-5). A simplified, clinically applicable version of LRS was also created that had comparable performance to the original LRS. CONCLUSIONS: LRS, augmenting the FRS, presents potential to improve intermediate-risk stratification and to predict atherosclerotic markers using a simple blood test, suitable for clinical application. This could facilitate the triage of individuals for noninvasive imaging such as CACS, fostering precision medicine in CVD prevention and management.

Published
2024

8. Physical Frailty: ICFSR International Clinical Practice Guidelines for Identification and Management

Author

Dent, E., Morley, J.E., Cruz-Jentoft, A.J., Woodhouse, L., Rodríguez-Mañas, L., Fried, L.P., Woo, J., Aprahamian, I., Sanford, A., Lundy, J., Landi, F., Beilby, J., Martin, F.C., Bauer, J.M., Ferrucci, L., Merchant, R.A., Dong, B., Arai, H., Hoogendijk, E.O., Won, C.W., Abbatecola, A., Cederholm, T., Strandberg, T., Gutiérrez Robledo, L.M., Flicker, L., Bhasin, S., Aubertin-Leheudre, M., Bischoff-Ferrari, H.A., Guralnik, J.M., Muscedere, J., Pahor, M., Ruiz, J., Negm, A.M., Reginster, J.Y., Waters, D.L., and Vellas, B.

Published
2019
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10. Erratum to: Screening for and Managing the Person with Frailty in Primary Care: ICFSR Consensus Guidelines

Author

Ruiz, J. G., Dent, E., Morley, John E., Merchant, R. A., Beilby, J., Beard, J., Tripathy, C., Sorin, M., Andrieu, S., Aprahamian, I., Arai, H., Aubertin-Leheudre, M., Bauer, J. M., Cesari, M., Chen, L.-K., Cruz-Jentoft, A. J., Barreto, P. De Souto, Dong, B., Ferrucci, L., Fielding, R., Flicker, L., Lundy, J., Reginster, J. Y., Rodriguez-Mañas, L., Rolland, Y., Sanford, A. M., Sinclair, A. J., Viña, J., Waters, D. L., Won, C. Won, Woo, J., and Vellas, B.

Published
2022
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13. Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption

Author

Cornelis, M C, Byrne, E M, Esko, T, Nalls, M A, Ganna, A, Paynter, N, Monda, K L, Amin, N, Fischer, K, Renstrom, F, Ngwa, J S, Huikari, V, Cavadino, A, Nolte, I M, Teumer, A, Yu, K, Marques-Vidal, P, Rawal, R, Manichaikul, A, Wojczynski, M K, Vink, J M, Zhao, J H, Burlutsky, G, Lahti, J, Mikkilä, V, Lemaitre, R N, Eriksson, J, Musani, S K, Tanaka, T, Geller, F, Luan, J, Hui, J, Mägi, R, Dimitriou, M, Garcia, M E, Ho, W-K, Wright, M J, Rose, L M, Magnusson, P K E, Pedersen, N L, Couper, D, Oostra, B A, Hofman, A, Ikram, M A, Tiemeier, H W, Uitterlinden, A G, van Rooij, F J A, Barroso, I, Johansson, I, Xue, L, Kaakinen, M, Milani, L, Power, C, Snieder, H, Stolk, R P, Baumeister, S E, Biffar, R, Gu, F, Bastardot, F, Kutalik, Z, Jacobs, Jr, D R, Forouhi, N G, Mihailov, E, Lind, L, Lindgren, C, Michaëlsson, K, Morris, A, Jensen, M, Khaw, K-T, Luben, R N, Wang, J J, Männistö, S, Perälä, M-M, Kähönen, M, Lehtimäki, T, Viikari, J, Mozaffarian, D, Mukamal, K, Psaty, B M, Döring, A, Heath, A C, Montgomery, G W, Dahmen, N, Carithers, T, Tucker, K L, Ferrucci, L, Boyd, H A, Melbye, M, Treur, J L, Mellström, D, Hottenga, J J, Prokopenko, I, Tönjes, A, Deloukas, P, Kanoni, S, Lorentzon, M, Houston, D K, Liu, Y, Danesh, J, Rasheed, A, Mason, M A, Zonderman, A B, Franke, L, Kristal, B S, Karjalainen, J, Reed, D R, Westra, H-J, Evans, M K, Saleheen, D, Harris, T B, Dedoussis, G, Curhan, G, Stumvoll, M, Beilby, J, Pasquale, L R, Feenstra, B, Bandinelli, S, Ordovas, J M, Chan, A T, Peters, U, Ohlsson, C, Gieger, C, Martin, N G, Waldenberger, M, Siscovick, D S, Raitakari, O, Eriksson, J G, Mitchell, P, Hunter, D J, Kraft, P, Rimm, E B, Boomsma, D I, Borecki, I B, Loos, R J F, Wareham, N J, Vollenweider, P, Caporaso, N, Grabe, H J, Neuhouser, M L, Wolffenbuttel, B H R, Hu, F B, Hyppönen, E, Järvelin, M-R, Cupples, L A, Franks, P W, Ridker, P M, van Duijn, C M, Heiss, G, Metspalu, A, North, K E, Ingelsson, E, Nettleton, J A, van Dam, R M, and Chasman, D I

Published
2015
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15. Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention

Author

Wang, Zhe, Emmerich, A., Pillon, N.J., Moore, T., Hemerich, D., Cornelis, M.C., Mazzaferro, E., Broos, S., Ahluwalia, T.S., Bartz, T.M., Bentley, A.R., Bielak, L.F., Chong, M., Chu, A.Y., Berry, D., Dorajoo, R., Dueker, N.D., Kasbohm, E., Feenstra, B., Feitosa, M.F., Gieger, C., Graff, M, Hall, L.M., Haller, T., Hartwig, F.P., Hillis, D.A., Huikari, V., Heard-Costa, N., Holzapfel, C., Jackson, A.U., Johansson, Å., Jørgensen, A.M., Kaakinen, M.A., Karlsson, R., Kerr, K.F., Kim, Boram, Koolhaas, C.M., Kutalik, Z., Lagou, V., Lind, P.A., Lorentzon, M., Lyytikäinen, L.P., Mangino, M., Metzendorf, C., Monroe, K.R., Pacolet, A., Pérusse, L., Pool, R., Richmond, R.C., Rivera, N.V., Robiou-du-Pont, S., Schraut, K.E., Schulz, C.A., Stringham, H.M., Tanaka, T., Teumer, A., Turman, C., Most, P.J. van der, Vanmunster, M., Rooij, F.J. van, Vliet-Ostaptchouk, J.V. Van, Zhang, Xiaoshuai, Zhao, J.H., Zhao, W, Balkhiyarova, Z., Balslev-Harder, M.N., Baumeister, S.E., Beilby, J., Blangero, J., Boomsma, D.I., Brage, S., Braund, P.S., Brody, J.A., Bruinenberg, M., Ekelund, U., Liu, C.T., Cole, J.W., Collins, F.S., Cupples, L.A., Esko, T., Enroth, S., Faul, J.D., Fernandez-Rhodes, L., Fohner, A.E., Franco, O.H., Galesloot, T.E., Gordon, S.D.S., Grarup, N., Hartman, C.A., Heiss, G., Hui, J., Illig, T., Jago, R., James, A., Joshi, P.K., Jung, T., Kähönen, M., Kilpeläinen, T.O., Koh, W.P., Kolcic, I., Kiemeney, L.A.L.M., Loos, R.J.F., Hoed, Marcel Den, Wang, Zhe, Emmerich, A., Pillon, N.J., Moore, T., Hemerich, D., Cornelis, M.C., Mazzaferro, E., Broos, S., Ahluwalia, T.S., Bartz, T.M., Bentley, A.R., Bielak, L.F., Chong, M., Chu, A.Y., Berry, D., Dorajoo, R., Dueker, N.D., Kasbohm, E., Feenstra, B., Feitosa, M.F., Gieger, C., Graff, M, Hall, L.M., Haller, T., Hartwig, F.P., Hillis, D.A., Huikari, V., Heard-Costa, N., Holzapfel, C., Jackson, A.U., Johansson, Å., Jørgensen, A.M., Kaakinen, M.A., Karlsson, R., Kerr, K.F., Kim, Boram, Koolhaas, C.M., Kutalik, Z., Lagou, V., Lind, P.A., Lorentzon, M., Lyytikäinen, L.P., Mangino, M., Metzendorf, C., Monroe, K.R., Pacolet, A., Pérusse, L., Pool, R., Richmond, R.C., Rivera, N.V., Robiou-du-Pont, S., Schraut, K.E., Schulz, C.A., Stringham, H.M., Tanaka, T., Teumer, A., Turman, C., Most, P.J. van der, Vanmunster, M., Rooij, F.J. van, Vliet-Ostaptchouk, J.V. Van, Zhang, Xiaoshuai, Zhao, J.H., Zhao, W, Balkhiyarova, Z., Balslev-Harder, M.N., Baumeister, S.E., Beilby, J., Blangero, J., Boomsma, D.I., Brage, S., Braund, P.S., Brody, J.A., Bruinenberg, M., Ekelund, U., Liu, C.T., Cole, J.W., Collins, F.S., Cupples, L.A., Esko, T., Enroth, S., Faul, J.D., Fernandez-Rhodes, L., Fohner, A.E., Franco, O.H., Galesloot, T.E., Gordon, S.D.S., Grarup, N., Hartman, C.A., Heiss, G., Hui, J., Illig, T., Jago, R., James, A., Joshi, P.K., Jung, T., Kähönen, M., Kilpeläinen, T.O., Koh, W.P., Kolcic, I., Kiemeney, L.A.L.M., Loos, R.J.F., and Hoed, Marcel Den

Abstract

Contains fulltext : 282313.pdf (Publisher’s version ) (Open Access), Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type II(A) muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.

Published
2022

16. Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease

Author

Cadby, G, Giles, C, Melton, PE, Huynh, K, Mellett, NA, Thy, D, Anh, N, Cinel, M, Smith, A, Olshansky, G, Wang, T, Brozynska, M, Inouye, M, McCarthy, NS, Ariff, A, Hung, J, Hui, J, Beilby, J, Dube, M-P, Watts, GF, Shah, S, Wray, NR, Lim, WLF, Chatterjee, P, Martins, I, Laws, SM, Porter, T, Vacher, M, Bush, A, Rowe, CC, Villemagne, VL, Ames, D, Masters, CL, Taddei, K, Arnold, M, Kastenmueller, G, Nho, K, Saykin, AJ, Han, X, Kaddurah-Daouk, R, Martins, RN, Blangero, J, Meikle, PJ, Moses, EK, Cadby, G, Giles, C, Melton, PE, Huynh, K, Mellett, NA, Thy, D, Anh, N, Cinel, M, Smith, A, Olshansky, G, Wang, T, Brozynska, M, Inouye, M, McCarthy, NS, Ariff, A, Hung, J, Hui, J, Beilby, J, Dube, M-P, Watts, GF, Shah, S, Wray, NR, Lim, WLF, Chatterjee, P, Martins, I, Laws, SM, Porter, T, Vacher, M, Bush, A, Rowe, CC, Villemagne, VL, Ames, D, Masters, CL, Taddei, K, Arnold, M, Kastenmueller, G, Nho, K, Saykin, AJ, Han, X, Kaddurah-Daouk, R, Martins, RN, Blangero, J, Meikle, PJ, and Moses, EK

Abstract

We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism and identify genetic variants associated with lipid species putatively in the mechanistic pathway for coronary artery disease (CAD). We quantified 596 lipid species in serum from 4,492 individuals from the Busselton Health Study. The discovery GWAS identified 3,361 independent lipid-loci associations, involving 667 genomic regions (479 previously unreported), with validation in two independent cohorts. A meta-analysis revealed an additional 70 independent genomic regions associated with lipid species. We identified 134 lipid endophenotypes for CAD associated with 186 genomic loci. Associations between independent lipid-loci with coronary atherosclerosis were assessed in ∼456,000 individuals from the UK Biobank. Of the 53 lipid-loci that showed evidence of association (P < 1 × 10-3), 43 loci were associated with at least one lipid endophenotype. These findings illustrate the value of integrative biology to investigate the aetiology of atherosclerosis and CAD, with implications for other complex diseases.

Published
2022

19. Additional file 1 of Common genetic variants do not predict recurrent events in coronary heart disease patients

Author

Thompson, P. L., Hui, J., Beilby, J., Palmer, L. J., Watts, G. F., West, M. J., Kirby, A., Marschner, S., Simes, R. J., Sullivan, D. R., White, H. D., Stewart, R., and Tonkin, A. M.

Abstract

Additional file 1: SNPs included in the custom designed Illumina Gold Gate array of 384 SNPs with minor allele frequency (MAF) > 1 plus additional SNPs included in the panel derived by Mega et al [8].

Published
2022
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33. Paediatric genomic testing: Navigating medicare rebatable genomic testing

Author

Sachdev, R, Field, M, Baynam, GS, Beilby, J, Berarducci, M, Berman, Y, Boughtwood, T, Cusack, MB, Fitzgerald, V, Fletcher, J, Freckmann, M-L, Grainger, N, Kirk, E, Lundie, B, Lunke, S, McGregor, L, Mowat, D, Parasivam, G, Tyrell, V, Wallis, M, White, SM, Ma, ASL, Sachdev, R, Field, M, Baynam, GS, Beilby, J, Berarducci, M, Berman, Y, Boughtwood, T, Cusack, MB, Fitzgerald, V, Fletcher, J, Freckmann, M-L, Grainger, N, Kirk, E, Lundie, B, Lunke, S, McGregor, L, Mowat, D, Parasivam, G, Tyrell, V, Wallis, M, White, SM, and Ma, ASL

Abstract

Genomic testing for a genetic diagnosis is becoming standard of care for many children, especially those with a syndromal intellectual disability. While previously this type of specialised testing was performed mainly by clinical genetics teams, it is increasingly being 'mainstreamed' into standard paediatric care. With the introduction of a new Medicare rebate for genomic testing in May 2020, this type of testing is now available for paediatricians to order, in consultation with clinical genetics. Children must be aged less than 10 years with facial dysmorphism and multiple congenital abnormalities or have global developmental delay or moderate to severe intellectual disability. This rebate should increase the likelihood of a genetic diagnosis, with accompanying benefits for patient management, reproductive planning and diagnostic certainty. Similar to the introduction of chromosomal microarray into mainstream paediatrics, this genomic testing will increase the number of genetic diagnoses, however, will also yield more variants of uncertain significance, incidental findings, and negative results. This paper aims to guide paediatricians through the process of genomic testing, and represents the combined expertise of educators, clinical geneticists, paediatricians and genomic pathologists around Australia. Its purpose is to help paediatricians navigate choosing the right genomic test, consenting patients and understanding the possible outcomes of testing.

Published
2021

37. Effects of endogenous estrogen on renal calcium and phosphate handling in elderly women

Author

Dick, I.M., Devine, A., Beilby, J., and Prince, R.L.

Subjects
Calcium, Dietary -- Research, Aged women -- Health aspects, Estrogen -- Research, Biological sciences
Abstract

High postmenopausal endogenous estrogen concentrations are an important determinant of preservation of bone mass and reduced fracture in elderly women. Calcium supplementation can also reduce bone loss in these patients, suggesting an interaction between estrogen deficiency and calcium balance. Potential mechanisms of estrogen on calcium transport include direct effects on the bone, the kidney, and the bowel. Previous studies have demonstrated effects of estrogen on renal phosphate handling. We have used a cross-sectional, population-based analysis of biochemical data obtained from ambulant elderly women to determine the association of endogenous estradiol with urine calcium and phosphorus excretion. The subjects were 293 postmenopausal women > 70 yr old. Factors associated with renal calcium and phosphate excretion were measured, including the filtered calcium and phosphate load, parathyroid hormone (PTH), estradiol, and sex hormone-binding globulin (SHBG). The free estradiol concentration (FE) was calculated from a previously described formula. A high plasma estradiol concentration ([r.sup.2] = 0.023, P = 0.01) and a high FE ([r.sup.2] = 0.045, P = 0.001) were associated with reduced renal calcium excretion. The estradiol and FE effect on renal calcium excretion remained significant after adjusting for calcium filtered at the glomerulus and serum PTH. A high FE was associated with a reduced renal phosphate threshold in univariate analysis ([r.sup.2] = 0.023, P = 0.010). The effect remained significant after adjustment for serum PTH. The size of the effect of the FE was of the same order of magnitude as the effect of PTH on reducing renal calcium excretion and increasing renal phosphate excretion. These data support in vitro and animal data demonstrating an effect of estradiol on renal calcium and phosphate handling and indicate that, in elderly postmenopausal women, the effect is of a similar magnitude to the well-recognized effects of PTH on these physiologically regulated parameters. estradiol; calcium homeostasis; phosphate homeostasis; renal tubular calcium reabsorption; osteoporosis

Published
2005

42. A polymorphism in the methylenetetrahydrofolate reductase gene predisposes to colorectal cancers with microsatellite instability. (Original Article)

Author

Shannon, B., Gnanasampanthan, S., Beilby, J., and Iacopetta, B.

Subjects
Colorectal cancer -- Development and progression -- Genetic aspects, Cancer -- Genetic aspects, Disease susceptibility -- Genetic aspects -- Development and progression, Health, Development and progression, Genetic aspects
Abstract

Background: The enzyme methylenetetrahydrofolate reductase (MTHFR) catalyses the formation of folate intermediates that are vital to methylation reactions. A polymorphic variant (TT) has been linked to reduced levels of plasma [...]

Published
2002

46. Erratum to: Screening for and Managing the Person with Frailty in Primary Care: ICFSR Consensus Guidelines

Author

Ruiz, J. G., primary, Dent, E., additional, Morley, John E., additional, Merchant, R. A., additional, Beilby, J., additional, Beard, J., additional, Tripathy, C., additional, Sorin, M., additional, Andrieu, S., additional, Aprahamian, I., additional, Arai, H., additional, Aubertin-Leheudre, M., additional, Bauer, J. M., additional, Cesari, M., additional, Chen, L.-K., additional, Cruz-Jentoft, A. J., additional, Barreto, P. De Souto, additional, Dong, B., additional, Ferrucci, L., additional, Fielding, R., additional, Flicker, L., additional, Lundy, J., additional, Reginster, J. Y., additional, Rodriguez-Mañas, L., additional, Rolland, Y., additional, Sanford, A. M., additional, Sinclair, A. J., additional, Viña, J., additional, Waters, D. L., additional, Won, C. Won, additional, Woo, J., additional, and Vellas, B., additional

Published
2020
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47. HIGHLIGHTS ACROSS MYOLOGY

Author

Edwards, S., primary, Ong, R., additional, Davis, M., additional, Allcock, R., additional, Androga, G., additional, Kamien, B., additional, Harrop, K., additional, Ravenscroft, G., additional, Fietz, M., additional, Pachter, N., additional, Beilby, J., additional, and Laing, N., additional

Published
2020
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