Medicine
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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
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Item Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries(Public Library of Science, 2018) Feitosa, M.F.; Kraja, A.T.; Chasman, D.I.; Sung, Y.J.; Winkler, T.W.; Ntalla, I.; Guo, X.; Franceschini, N.; Cheng, C.Y.; Sim, X.; Vojinovic, D.; Marten, J.; Musani, S.K.; Li, C.; Bentley, A.R.; Brown, M.R.; Scwander, K.; Richard, M.A.; Noordam, R.; Aschard, H.; Bartz, T.M.; Bielak, L.F.; Dorajoo, R.; Fishaer, V.; Hartwig, F.P.; Horimoto, A.R.V.R.; Lohman, K.K.; Manning, A.K.; Rankinen, T.; Smith, A.V.; Tajiddin, S.M.; Wojczynski, M.K.; Alver, M.; Boissel, M.; Cai, Q.; Campbell, A.; Chai, J.F.; Chen, X.; Divers, J.; Gao, C.; Goel, A.; Hagemeijer, Y.; Harris, S.E.; He, M.; Hsu, F.C.; Jackson, A.U.; Kahonen, M.; Kasturiratne, A.; Komulainen, P.; Kuhnel, B.; Laguzzi, F.; Luan, J.; Matoba, N.; Nolte, I.M.; Padmanabhan, S.; Riaz, M.; Rueedi, R.; Robino, A.; Said, M.A.; Scott, R.A.; Soffer, T.; Stancakova, A.; Takeuchi, F.; Tayo, B.O.; van de Most, P.J.; Varga, T.V.; Vitart, V.; Wang, Y.; Ware, E.B.; Warren, H.R.; Weiss, S.; Wen, W.; Yanek, L.R.; Zhang, W.; Zhao, J.H.; Afaq, S.; Amin, N.; Amini, M.; Arking, D.E.; Aung, T.; Boerwinkle, E.; Borecki, I.; Broecki, I.; Broeckel, U.; Brown, M.; Brumat, M.; Burke, G.L.; Canouil, M.; Chakravarthi, A.; Charumathi, S.; Ida Chen, Y.D.; Connel, J.M.; Correa, A.; de Las Fuentes, L.; de Mutsert, R.; de Silva, H.J.; Deng, X.; Ding, J.; Duan, Q.; Eaton, C.B.; Ehret, G.; Eppinga, R.N.; Evangelou, E.; Faul, J.D.; Felix, S.B.; Forouhi, N.G.; Forrester, T.; Franco, O.H.; Friedlander, Y.; Gandin, I.; Gao, H.; Ghanbari, M.; Gigante, B.; Gu, C.C.; Gu, D.; Hagenaars, S.P.; Halmans, G.; Harris, T.B.; He, J.; Heikkinen, S.; Heng, C.K.; Hirata, M.; Howard, B.V.; Ikram, M.A.; InterAct Consortium; John, U.; Katsuya, T.; Lakka, T.A.; Langefeld, C.D.; Langenberg, C.; Launer, L.J.; Lehne, B.; Lewis, C.E.; Li, Y.; Lin, S.; Lin, U.; Liu, J.; Liu, J.; Loh, M.; Louie, T.; Magi, R.; McKenzie, C.A.; Meitinger, T.; Metspalu, A.; Milaneschi, Y.; Milani, L.; mohlke, K.L.; Momozawa, Y.; Nalls, M.A.; Nelson, C.P.; Sotoodehnia, N.; Norris, J.M.; O'Connel, J.R.; Palmer, N.D.; Perls, T.; Pedersen, N.L.; Peters, A.; Peyser, P.A.; Poulter, N.; Raffel, L.J.; Raitakari, O.T.; Roll, K.; Rose, L.M.; Rosendaal, F.R.; Rotter, J.I.; Schimidit, C.O.; Schreiner, P.J.; Schupf, N.; Scott, W.R.; Sever, P.S.; Shi, Y.; Sidney, S.; Sims, M.; Sitlani, C.M.; Smith, J.A.; Snieder, H.; Starr, J.M.; Strauch, K.; Stringham, H.M.; Tan, N.Y.Q.; Tang, H.; Taylor, K.D.; Teo, Y.Y.; Tham, Y.C.; Turner, S.C.; Uitterlinden, A.G.; Vollenweider, P.; Waldenberger, M.; Wang, L.; Wang, Y.X.; Wei, W.B.; Williams, C.; Yao, J.; Yuan, J.M.; Zhao, W.; Zonderman, A.B.; Becker, D.M.; Boehnke, M.; Bowden, D.W.; Chambers, J.C.; Deary, I.J.; Esco, T.; Farall, M.; Frankd, P.W.; Freedman, B.I.; Froguel, P.; Gasparini, P.; Gieger, C.; Jonas, J.B.; Kamatani, Y.; Kato, N.; Kooner, J.S.; Kutalik, Z.; Laakso, M.; Laurie, C.C.; Leander, K.; Lehtimaki, T.; Study, L.C.; Magnusson, P.K.E.; Olderhinkel, A.J.; Penninx, B.W.J.H.; Polasek, O.; Porteous, D.J.; Rauramaa, R.; Ssamani, N.J.; Scott, J.; Shu, X.O.; van der Harst, P.; Wagenknecht, L.E.; Wareham, N.J.; Watkins, H.; Weir, D.R.; Wickremasinghe, A.R.; Wu, T.; Zheng, W.; Bouchard, C.; Christensen, K.; Evans, M.K.; Gudnason, V.; Horta, B.L.; Kardia, S.L.R.; Liu, Y.; Pereira, A.C.; Psaty, B.M.; Ridker, P.M.; van Dam, R.M.; Gauderman, W.J.; Zhu, X.; Mook-Kanamori, D.O.; Fornage, M.; Rotimi, C.N.; Cupples, L.A.; Kelly, T.N.; Fox, E.R.; Hayward, C.; van Duijn, C.M.; Tai, E.S.; Wong, T.Y.; Kooperberg, C.; Palmas, W.; Rice, K.; Morrison, A.C.; Elliott, P.; Caulfield, M.J.; Munroe, P.B.; Rao, D.C.; Province, M.A.; Levy, D.Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertensionItem Patterns of alcohol use and occurrence of alcoholic fatty liver disease: a prospective, community cohort, 7-year follow-up study(Sri Lanka Medical Association, 2017) Niriella, M.A.; de Silva, S.T.; Kasturiratne, A.; Perera, K.R.; Subasinghe, S.K.C.E.; Kodisinghe, S.K.; Piyaratna, T.A.C.L.; Vithiya, K.; Dassanayake, A.S.; de Silva, A.P.; Pathmeswaran, A.; Wickremasinghe, A.R.; Kato, N.; de Silva, H.J.INTRODUCTION & OBJECTIVES: Data is limited on alcoholic fatty liver disease (AFLD). We investigated patterns of alcohol use and AFLD, among urban, adult, Sri Lankans. METHODS: Study population (selected by age-stratified random sampling from Ragama MOH-area) was screened initially in 2007 (35-64 years) and re-evaluated in 2014. On both occasions they were assessed by structured-interview, anthropometric measurements, liver ultrasound, biochemical and serological tests. AFLD was diagnosed on ultrasound criteria, unsafe alcohol consumption (Asian standards: males>14units, females>7units per week) and absence of hepatitis B/C markers. Controls were individuals with unsafe alcohol consumption, but had no ultrasound criteria of AFLD. Case-control genetic-association for PNPLA3 (rs738409) polymorphism for AFLD was performed. RESULTS: A total of 2983/3012 (99%) had complete data. 272/2983(9.1%) were unsafe-drinkers [males- 70; mean-age 51.9 (SD-8.0) years]. 86/2983 (2.9%) of the cohort and 86/272 (31.6%) of unsafe-drinkers had AFLD [males-85; mean-age 50.2 (SD-8.6) years]. Males [p<0.001], increased waist circumference (WC) [p=0.001], BMI>23kg/m2 [p<0.001], raised triglycerides (TG) [p<0.001], low education level (LEL-not completed secondary-education) [p<0.01] and low monthly household-income (23kg/m2 [p<0.001], raised TG [p<0.001] and LEL [p<0.05] independently predicted incident-AFLD. The genetic association study [133-cases (combined 2007-2014), 97-controls] showed no association with AFLD at PNPLA3 (rs738409). CONCLUSION: The prevalence of AFLD was 2.9% in 2007 and annual incidence among heavy drinkers, after 7-year follow-up was 5.7%. Incident-AFLD was associated with males, obesity, raised TG and LEL.