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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 Improving psychological well-being among healthcare workers during the COVID-19 pandemic with an online mindfulness intervention: A randomised waitlist-controlled trial(Wiley, 2024) Baminiwatta, A.; Fernando, R.; Solangaarachchi, I.; Abayabandara-Herath, T.; Wickremasinghe, A.R.; Hapangama, A.The high prevalence of psychological problems observed among healthcare workers (HCWs) during the COVID-19 pandemic called for interventions to safeguard their mental health. We assessed the effectiveness of a 6-week online mindfulness-based intervention in improving well-being and reducing stress among HCWs in Sri Lanka. Eighty HCWs were recruited and randomised into two groups: waitlist-control (WLC) and intervention groups. In the intervention, 1-hour online sessions were conducted at weekly intervals and participants were encouraged to do daily home practice. Stress and well-being were measured pre- and post-intervention using the Perceived Stress Scale and WHO-5 Well-being Index, respectively. One-way analysis of covariance was used to evaluate the effectiveness, in both intention-to-treat (ITT) and complete-case (CC) analyses. A significantly greater improvement in well-being occurred in the intervention arm compared to WLC on both ITT (p = .002) and CC analyses (p < .001), with medium-to-large effect sizes (partial η2 = .117-.278). However, the reduction in stress following the intervention was not significant compared to the WLC group on both ITT (p = .636) and CC analyses (p = .262). In the intervention arm, the median number of sessions attended by participants was 3. Low adherence to the intervention may have contributed to the apparent non-significant effect on stress.Item Effect of virgin coconut oil supplementation on cognition of individuals with mild-to-moderate alzheimer's disease in Sri Lanka (VCO-AD study): A randomized placebo-controlled trial(IOS Press, 2023) Fernando, M.G.; Silva, R.; Fernando, W.M.A.D.B.; de Silva, H.A.; Wickremasinghe, A.R.; Dissanayake, A.S.; Sohrabi, H.R.; Martins, R.N.; Williams, S.S.BACKGROUND: Virgin coconut oil (VCO) is a potential therapeutic approach to improve cognition in Alzheimer’s disease (AD) due to its properties as a ketogenic agent and antioxidative characteristics. OBJECTIVE: This study aimed to investigate the effect of VCO on cognition in people with AD and to determine the impact of apolipoprotein E (APOE) ɛ4 genotype on cognitive outcomes. METHODS: Participants of this double-blind placebo-controlled trial (SLCTR/2015/018, 15.09.2015) were 120 Sri Lankan individuals with mild-to-moderate AD (MMSE = 15-25), aged > 65 years, and they were randomly allocated to treatment or control groups. The treatment group was given 30 mL/day of VCO orally and the control group, received similar amount of canola oil, for 24 weeks. The Mini-Mental Sate Examination (MMSE) and Clock drawing test were performed to assess cognition at baseline and at the end of the intervention. Blood samples were collected and analyzed for lipid profile and glycated hemoglobin (HbA1 C) levels.∥ RESULTS: There were no significant difference in cognitive scores, lipid profile, and HbA1 C levels between VCO and control groups post-intervention. The MMSE scores, however, improved among APOE ɛ4 carriers who had VCO, compared to non-carriers (2.37, p = 0.021). APOE ɛ4 status did not influence the cognitive scores in the control group. The attrition rate was 30%.∥ CONCLUSION: Overall, VCO did not improve cognition in individuals with mild-to-moderate AD following a 24-week intervention, compared to canola oil. However, it improved the MMSE scores in APOE ɛ4 carriers. Besides, VCO did not compromise lipid profile and HbA1 C levels and is thus safe to consume.Item Elimination of malaria from Sri Lanka and beyond; lessons for other countries in elimination phase(Sri Lanka Medical Association, 2023) Wickremasinghe, A.R.Elimination of malaria in 2012 was a major achievement in post-independent Sri Lanka. Sri Lanka missed a golden opportunity in 1963 when only 17 cases of malaria were reported in the country, but could not sustain the momentum resulting in a major resurgence in 1967/69. With the resurgence, the then malaria eradication programme was reverted back to a control programme that lasted for another 30 years. The WHO's Roll Back Malaria Initiative launched in 1998 provided a renewed interest in malaria control and subsequent elimination. With targeted control activities, the burden of malaria started to decrease since year 2000. Although Sri Lanka had reached pre-elimination status as early as 2004, the ongoing separatist war at that time prevented a country-wide elimination drive being implemented. With cessation of hostilities in 2009 and Global Fund financing, both of which were crucial inputs, an elimination drive was launched in September 2009 which eventually eliminated indigenous malaria in November 2012 with malaria-free certification by WHO being obtained in September 2016. Since malaria elimination, the country forged on to the prevention of re-establishment phase primarily focusing on good public practice that included intensified surveillance, both parasitological and entomological; quality assured diagnostic and treatment services; and advocacy at various level including doctors. Despite these measures, an introduced case and an induced case of malaria have been reported. A new vector of urban malaria, Anopheles stephensi, was reported in December 2016. Prevention of re-establishment of malaria should be kept in the radar of public health until malaria is eradicated.Item REACh for the preschoolers; a developmental assessment tool for 2-5 year old children in Sri Lanka(BioMed Central, 2023) Caldera, A.V.; Wickremasinghe, A.R.; Muttiah, N.; Godamunne, P.K.S.; Jayasena, B.N.; Chathurika, L.K.E.; Perera, K.M.N.; Mendis, M.; Tilakarathne, D.; Peiris, M.K.R.R.; Wijesinghe, T.; Senarathna, N.E.; Saubhagya, W.D.L.; Chandraratne, M.; Sumanasena, S.P.BACKGROUND: Preschool children in low resource settings are at higher risk of missing developmental potential due to the lack of standardized and validated methods for the timely detection of children with developmental delays or neurodevelopmental disorders. The preschool teacher is a non-specialist resourceful link within the community to detect and offer interventions early. This paper discusses the preliminary iteration of designing and testing the psychometric properties of a developmental assessment for children aged 24 to 60 months in Sri Lanka. This assessment is designed to be conducted by preschool teachers in their preschool setting. METHODS: Three processes followed: 1. Designing and development of the Ragama Early Assessment for Children (REACh) complete preschool developmental assessment and a tool kit 2. Testing and training teachers on conducting the REACh assessment 3. Preliminary assessment of the psychometric properties including content validity, internal consistency, interrater reliability and concurrent validity. RESULTS: A literature search identified 11 assessments and 542 items representing cognitive, social-emotional and adaptive, language and motor domains. Content validity was assessed to select and adapt items. A complete assessment tool was designed to be administered in four settings within the preschool. This was further improved during pre and pilot testing and teacher training. Cronbach's alpha measuring internal consistency was > 0.70 for cognitive, language, social-emotional and adaptive domains across all three age groups in 1809 children. Interrater reliability was > 65% for age groups 36-47 and 47- 60 months. Concurrent validity using a clinical gold standard demonstrated sensitivity of more than 0.75 for all age groups with variable specificities (24-35 months: 0.71, 36- 47 months: 0.43 and 48-60 months: 0.67) assessed in 75 children. CONCLUSIONS: This culturally and linguistically adapted tool was tested nationally in Sri Lanka. The inte-rrater reliability between teachers and research assistants was higher than 65% for all domains in children more than 36 months. The preliminary iteration confirms it as an acceptable screening assessment for all age groups but with significantly lower specificity in the 36-47 month age group. Further improvement in certain domains together with intense teacher training is likely to enhance the validity and reliability of the assessment.Item Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis(BioMed Central Ltd, 2022) Kanoni, S.; Graham, S.E.; Wang, Y.; Surakka, I.; Ramdas, S.; Zhu, X.; Clarke, S.L.; Bhatti, K.F.; Vedantam, S.; Winkler, T.W.; Locke, A.E.; Marouli, E.; Zajac, G.J.M.; Wu, K.H.; Ntalla, I.; Hui, Q.; Klarin, D.; Hilliard, A.T.; Wang, Z.; Xue, C.; Thorleifsson, G.; Helgadottir, A.; Gudbjartsson, D.F.; Holm, H.; Olafsson, I.; Hwang, M.Y.; Han, S.; Akiyama, M.; Sakaue, S.; Terao, C.; Kanai, M.; Zhou, W.; Brumpton, B.M.; Rasheed, H.; Havulinna, A.S.; Veturi, Y.; Pacheco, J.A.; Rosenthal, E.A.; Lingren, T.; Feng, Q.; Kullo, I.J.; Narita, A.; Takayama, J.; Martin, H.C.; Hunt, K.A.; Trivedi, B.; Haessler, J.; Giulianini, F.; Bradford, Y.; Miller, J.E.; Campbell, A.; Lin, K.; Lin, K.; Millwood, I.Y.; Rasheed, A.; Hindy, G.; Faul, J.D.; Zhao, W.; Weir, D.R.; Turman, C.; Huang, H.; Graff, M.; Choudhury, A.; Sengupta, D.; Mahajan, A.; Brown, M.R.; Zhang, W.; Yu, K.; Schmidt, E.M.; Pandit, A.; Gustafsson, S.; Yin, X.; Luan, J.; Zhao, J.H.; Matsuda, F.; Jang, H.M.; Yoon, K.; Medina-Gomez, C.; Pitsillides, A.; Hottenga, J.J.; Wood, A.R.; Ji, Y.; Gao, Z.; Haworth, S.; Yousri, N.A.; Mitchell, R.E.; Chai, J.F.; Aadahl, M.; Bjerregaard, A.A.; Yao, J.; Manichaikul, A.; Hwu, C.M.; Hung, Y.J.; Warren, H.R.; Ramirez, J.; Bork-Jensen, J.; Kårhus, L.L.; Goel, A.; Sabater-Lleal, M.; Noordam, R.; Mauro, P.; Matteo, F.; McDaid, A.F.; Marques-Vidal, P.; Wielscher, M.; Trompet, S.; Sattar, N.; Møllehave, L.T.; Munz, M.; Zeng, L.; Huang, J.; Yang, B.; Poveda, A.; Kurbasic, A.; Lamina, C.; Forer, L.; Scholz, M.; Galesloot, T.E.; Bradfield, J.P.; Ruotsalainen, S.E.; Daw, E.; Zmuda, J.M.; Mitchell, J.S.; Fuchsberger, C.; Christensen, H.; Brody, J.A.; Vazquez-Moreno, M.; Feitosa, M.F.; Wojczynski, M.K.; Wang, Z.; Preuss, M.H.; Mangino, M.; Christofidou, P.; Verweij, N.; Benjamins, J.W.; Engmann, J.; Tsao, N.L.; Verma, A.; Slieker, R.C.; Lo, K.S.; Zilhao, N.R.; Le, P.; Kleber, M.E.; Delgado, G.E.; Huo, S.; Ikeda, D.D.; Iha, H.; Yang, J.; Liu, J.; Demirkan, A.; Leonard, H.L.; Marten, J.; Frank, M.; Schmidt, B.; Smyth, L.J.; Cañadas-Garre, M.; Wang, C.; Nakatochi, M.; Wong, A.; Hutri-Kähönen, N.; Lyssenko, V.; Fernandez-Lopez, J.C.; Huerta-Chagoya, A.; Xia, R.; Sim, X.; Nongmaithem, S.S.; Bayyana, S.; Stringham, H.M.; Irvin, M.R.; Oldmeadow, C.; Kim, H.N.; Ryu, S.; Timmers, P,R,H,J,; Arbeeva, L.; Dorajoo, R.; Lange, L.A.; Prasad, G.; Lorés-Motta, L.; Pauper, M.; Long, J.; Li, X.; Theusch, E.; Takeuchi, F.; Spracklen, C.N.; Loukola, A.; Bollepalli, S.; Warner, S.C.; Wang, Y.X.; Wei, W.B.; Nutile, T.; Ruggiero, D.; Sung, Y.J.; Chen, S.; Liu, F.; Yang, J.; Kentistou, K.A.; Banas, B.; Nardone, G.G.; Meidtner, K.; Bielak, L.F.; Smith, J.A.; Hebbar, P.; Farmaki, A.E.; Hofer, E.; Lin, M.; Concas, M.P.; Vaccargiu, S.; van der Most, P.J.; Pitkänen, N.; Cade, B.E.; van der Laan, S.W.; Chitrala, K.N.; Weiss, S.; Bentley, A.R.; Doumatey, A.P.; Adeyemo, A.A.; Lee, J.Y.; Petersen, E.R.B.; Nielsen, A.A.; Choi, H.S.; Nethander, M.; Freitag-Wolf, S.; Southam, L.; Rayner, N.W.; Wang, C.A.; Lin, S.Y.; Wang, J.S.; Couture, C.; Lyytikäinen, L.P.; Nikus, K.; Cuellar-Partida, G.; Vestergaard, H.; Hidalgo, B.; Giannakopoulou, O.; Cai, Q.; Obura, M.O.; van Setten, J.; Li, X.; Liang, J.; Tang, H.; Terzikhan, N.; Shin, J.H.; Jackson, R.D.; Reiner, A.P.; Martin, L.W.; Chen, Z.; Li, L.; Kawaguchi, T.; Thiery, J.; Bis, J.C.; Launer, L.J.; Li, H.; Nalls, M.A.; Raitakari, O.T.; Ichihara, S.; Wild, S.H.; Nelson, C.P.; Campbell, H.; Jäger, S.; Nabika, T.; Al-Mulla, F.; Niinikoski, H.; Braund, P.S.; Kolcic, I.; Kovacs, P.; Giardoglou, T.; Katsuya, T.; de Kleijn, D.; de Borst, G.J.; Kim, E.K.; Adams, H.H.H.; Ikram, M.A.; Zhu, X.; Asselbergs, F.W.; Kraaijeveld, A.O.; Beulens, J.W.J.; Shu, X.O.; Rallidis, L.S.; Pedersen, O.; Hansen, T.; Mitchell, P.; Hewitt, A.W.; Kähönen, M.; Pérusse, L.; Bouchard, C.; Tönjes, A.; Chen, Y.I.; Pennell, C.E.; Mori, T.A.; Lieb, W.; Franke, A.; Ohlsson, C.; Mellström, D.; Cho, Y.S.; Lee, H.; Yuan, J.M.; Koh, W.P.; Rhee, S.Y.; Woo, J.T.; Heid, I.M.; Stark, K.J.; Zimmermann, M.E.; Völzke, H.; Homuth, G.; Evans, M.K.; Zonderman, A.B.; Polasek, O.; Pasterkamp, G.; Hoefer, I.E.; Redline, S.; Pahkala, K.; Oldehinkel, A.J.; Snieder, H.; Biino, G.; Schmidt, R.; Schmidt, H.; Bandinelli, S.; Dedoussis, G.; Thanaraj, T.A.; Kardia, S.L.R.; Peyser, P.A.; Kato, N.; Schulze, M.B.; Girotto, G.; Böger, C.A.; Jung, B.; Joshi, P.K.; Bennett, D.A.; de Jager, P.L.; Lu, X.; Mamakou, V.; Brown, M.; Caulfield, M.J.; Munroe, P.B.; Guo, X.; Ciullo, M.; Jonas, J.B.; Samani, N.J.; Kaprio, J.; Pajukanta, P.; Tusié-Luna, T.; Aguilar-Salinas, C.A.; Adair, L.S.; Bechayda, S.A.; de Silva, H.J.; Wickremasinghe, A.R.; Krauss, R.M.; Wu, J.Y.; Zheng, W.; Hollander, A.I.; Bharadwaj, D.; Correa, A.; Wilson, J.G.; Lind, L.; Heng, C.K.; Nelson, A.E.; Golightly, Y.M.; Wilson, J.F.; Penninx, B.; Kim, H.L.; Attia, J.; Scott, R.J.; Rao, D.C.; Arnett, D.K.; Hunt, S.C.; Walker, M.; Koistinen, H.A.; Chandak, G.R.; Mercader, J.M.; Costanzo, M.C.; Jang, D.; Burtt, N.P.; Villalpando, C.G.; Orozco, L.; Fornage, M.; Tai, E.; van Dam, R.M.; Lehtimäki, T.; Chaturvedi, N.; Yokota, M.; Liu, J.; Reilly, D.F.; McKnight, A.J.; Kee, F.; Jöckel, K.H.; McCarthy, M.I.; Palmer, C.N.A.; Vitart, V.; Hayward, C.; Simonsick, E.; van Duijn, C.M.; Jin, Z.B.; Qu, J.; Hishigaki, H.; Lin, X.; März, W.; Gudnason, V.; Tardif, J.C.; Lettre, G.; Hart, L.M.; Elders, P.J.M.; Damrauer, S.M.; Kumari, M.; Kivimaki, M.; van der Harst, P.; Spector, T.D.; Loos, R.J.F.; Province, M.A.; Parra, E.J.; Cruz, M.; Psaty, B.M.; Brandslund, I.; Pramstaller, P.P.; Rotimi, C.N.; Christensen, K.; Ripatti, S.; Widén, E.; Hakonarson, H.; Grant, S.F.A.; Kiemeney, L.A.L.M.; de Graaf, J.; Loeffler, M.; Kronenberg, F.; Gu, D.; Erdmann, J.; Schunkert, H.; Franks, P.W.; Linneberg, A.; Jukema, J.W.; Khera, A.V.; Männikkö, M.; Jarvelin, M.R.; Kutalik, Z.; Francesco, C.; Mook-Kanamori, D.O.; van Dijk, K.W.; Watkins, H.; Strachan, D.P.; Grarup, N.; Sever, P.; Poulter, N.; Chuang, L.M.; Rotter, J.I.; Dantoft, T.M.; Karpe, F.; Neville, M.J.; Timpson, N.J.; Cheng, C.Y.; Wong, T.Y.; Khor, C.C.; Li, H.; Sabanayagam, C.; Sabanayagam, C.; Peters, A.; Gieger, C.; Hattersley, A.T.; Pedersen, N.L.; Magnusson, P.K.E.; Boomsma, D.I.; Willemsen, A.H.M.; Cupples, L.; van Meurs, J.B.J.; Ghanbari, M.; Gordon-Larsen, P.; Huang, W.; Kim, Y.J.; Tabara, Y.; Wareham, N.J.; Langenberg, C.; Zeggini, E.; Kuusisto, J.; Laakso, M.; Ingelsson, E.; Abecasis, G.; Chambers, J.C.; Kooner, J.S.; de Vries, P.S.; Morrison, A.C.; Hazelhurst, S.; Ramsay, M.; North, K.E.; Daviglus, M.; Kraft, P.; Martin, N.G.; Whitfield, J.B.; Abbas, S.; Saleheen, D.; Walters, R.G.; Holmes, M.V.; Black, C.; Smith, B.H.; Baras, A.; Justice, A.E.; Buring, J.E.; Ridker, P.M.; Chasman, D.I.; Kooperberg, C.; Tamiya, G.; Yamamoto, M.; van Heel, D.A.; Trembath, R.C.; Wei, W.Q.; Jarvik, G.P.; Namjou, B.; Hayes, M.G.; Ritchie, M.D.; Jousilahti, P.; Salomaa, V.; Hveem, K.; Åsvold, B.O.; Kubo, M.; Kamatani, Y.; Okada, Y.; Murakami, Y.; Kim, B.J.; Thorsteinsdottir, U.; Stefansson, K.; Zhang, J.; Chen, Y.; Ho, Y.L.; Lynch, J.A.; Rader, D.J.; Tsao, P.S.; Chang, K.M.; Cho, K.; O'Donnell, C.J.; Gaziano, J.M.; Wilson P.W.F.; Frayling, T.M.; Hirschhorn, J.N.; Kathiresan, S.; Mohlke, K.L.; Sun, Y.V.; Morris, A.P.; Boehnke, M.; Brown, C.D.; Natarajan, P.; Deloukas, P.; Willer, C.J.; Assimes, T.L.; Peloso, G.M.BACKGROUND: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. RESULTS: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. CONCLUSIONS: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Item Prevalence of asthma and its symptoms in Sri Lankan adults.(BioMed Central, London, 2022) Gunasekera, K.D.; Amarasiri, W.A.D.L.; Undugodage, U.C.M.; Silva, H.K.M.S.; Sadikeen, A.; Gunasinghe, W.; Fernando, A.; Perera, B.P.R.; Wickremasinghe, A.R.BACKGROUND: Data on adult asthma is scarce in Sri Lanka. The objective of this study was to estimate the prevalence of asthma and its symptoms in adult Sri Lankans. METHODS: A cross-sectional study using a translated version of the European Community Respiratory Health Survey screening questionnaire on subjects ≥ 18 years from 7 provinces in Sri Lanka was conducted. The asthma was defined as "wheezing in the past 12 months (current wheeze)", self-reported asthma attack in the past 12 months or on current asthma medication use. RESULTS: Among 1872 subjects (45.1% males, 48.8% between 18-44 years of age), the prevalence of current wheeze was 23.9% (95%CI: 22.0%-25.9%), self-reported asthma was 11.8% (95%CI: 10.3%-13.2%) and current asthma medication use was 11.1% (95% CI: 9.6%-12.5%). The prevalences were higher in adults > 44 years, 31.4% positively responded to any of the above questions (95%CI: 29.3%-33.4%) and 60.9% of current wheezers did not report having asthma whilst 38.2% used asthma medication. Among current wheezers, 80.1% had at least one other symptom, cough being the commonest. Those with no current wheeze, self-reported asthma and on current asthma medication use, 30%, 35.9% and 36.6%, respectively, reported at least one other symptom. Smokers comprises 22% current wheezers, 20.6% of self-reported asthmatics and 18.7% of current asthma medication users. CONCLUSIONS: The prevalence of asthma in Sri Lankan adults is higher than the other South Asian countries and higher in the older age group. A significant percentage of symptomatic individuals did not report having asthma or being on medication.Item A saturated map of common genetic variants associated with human height(Nature Publishing Group, 2022) Vedantam, S.; Marouli, E.; Sidorenko, J.; Bartell, E.; Sakaue, S.; Graff, M.; Eliasen, A.U.; Jiang, Y.; Raghavan, S.; Miao, J.; Arias, J.D.; Graham, S.E.; Mukamel, R.E.; Spracklen, C.N.; Yin, X.; Chen, S.H.; Ferreira, T.; Highland, H.H.; Ji, Y.; Karaderi. T,; Lin, K.; Lüll, K.; Malden, D.E.; Medina-Gomez, C.; Machado, M.; Moore, A.; Rüeger, S.; Sim. X,; Vrieze, S.; Ahluwalia, T.S.; Akiyama, M.; Allison, M.A.; Alvarez, M.; Andersen, M.K.; Ani, A.; Appadurai, V.; Arbeeva, L.; Bhaskar, S.; Bielak, L.F.; Bollepalli, S.; Bonnycastle, L.L.; Bork-Jensen, J.; Bradfield, J.P.; Bradford, Y.; Braund, P.S.; Brody, J.A.; Burgdorf, K.S.; Cade, B.E.; Cai, H.; Cai, Q.; Campbell, A.; Cañadas-Garre, M.; Catamo, E.; Chai, J.F.; Chai, X.; Chang, L.C.; Chen, C.H.; Chesi, A.; Choi, S.H.; Chung, R.H.; Cocca, M.; Concas, M.P.; Couture, C.; Cuellar-Partida, G.; Danning, R.; Daw, E.W.; Degenhard, F.; Delgado, G.E.; Delitala, A.; Demirkan, A.; Deng, X.; Devineni, P.; Dietl, A.; Dimitriou, M.; Dimitrov, L.; Dorajoo, R.; Ekici, A.B.; Engmann, J.E.; Fairhurst-Hunter, Z.; Farmaki, A.E.; Faul, J.D.; Fernandez-Lopez, J.C.; Forer, L.; Francescatto, M.; Freitag-Wolf, S.; Fuchsberger, C.; Galesloot, T.E.; Gao, Y.; Gao, Z.; Geller, F.; Giannakopoulou, O.; Giulianini,F.; Gjesing, A.P.; Goel, A.; Gordon, S.D.; Gorski, M.; Grove, J.; Guo, X.; Gustafsson, S.; Haessler, J.; Hansen, T.F.; Havulinna, A.S.; Haworth, S.J.; He, J.; Heard-Costa, N.; Hebbar, P.; Hindy, G.; Ho, Y.A.; Hofer, E.; Holliday, E.; Horn, K.; Hornsby, W.E.; Hottenga, J.J.; Huang, H.; Huang, J.; Huerta-Chagoya, A.; Huffman, J.E.; Hung, Y.J.; Huo, S.; Hwang, M.Y.; Ha, H.; Ikeda, D.D.; Isono, M.; Jackson, A.U.; Jäger, S.; Jansen, I.E.; Johansson, I.; Jonas, J.B.; Jonsson, A.; Jørgensen, T.; Kalafati, I.P.; Kanai, M.; Kanoni, S.; Kårhus, L.L.; Kasturiratne, A.; Katsuya, T.; Kawaguchi, T.; Kember, R.L.; Kentistou, K.A.; Kim, H.N.; Kim, Y.J.; Kleber, M.E.; Knol, M.J.; Kurbasic, A.; Lauzon, M.; Le, P.; Lea, R.; Lee, J.Y.; Leonard, H.L.; Li, S.A.; Li, X.; Li, X.; Liang, J.; Lin, H.; Lin, S.Y.; Liu, J.; Liu, X.; Lo, K.S.; Long, J.; Lores-Motta, L.; Luan, J.; Lyssenko, V.; Lyytikäinen, L.P.; Mahajan, A.; Mamakou, V.; Mangino, M.; Manichaikul, A.; Marten, J.,; Mattheisen, M.; Mavarani, L.; McDaid, A.F.; Meidtner, K.; Melendez, T.L.; Mercader, J.M.; Milaneschi, Y.; Miller, J.E.; Millwood, I.Y.; Mishra, P.P.; Mitchell, R.E.; Møllehave, L.T.; Morgan, A.; Mucha, S.; Munz, M.; Nakatochi, M.; Nelson, C.P.; Nethander, M.; Nho, C.W.; Nielsen, A.A.; Nolte, I.M.; Nongmaithem, S.S.; Noordam, R.; Ntalla, I.; Nutile, T.; Pandit, A.; Christofidou, P.; Pärna, K.; Pauper, M.; Petersen, E.R.B.; Petersen, L.V.; Pitkänen, N.; Polašek, O.; Poveda, A.; Preuss, M.H.; Pyarajan, S.; Raffield, L.M.; Rakugi, H.; Ramirez, J.; Rasheed, A.; Raven, D.; Rayner, N.W.; Riveros, C.; Rohde, R.; Ruggiero, D.; Ruotsalainen, S.E.; Ryan, K.A.; Sabater-Lleal, M.; Saxena, R.; Scholz, M.; Sendamarai, A.; Shen, B.; Shi, J.; Shin, J.H.; Sidore, C.; Sitlani, C.M.; Slieker, R.C.; Smit, R.A.J.; Smith, A.V.; Smith, J.A.; Smyth, L.J.; Southam, L.; Steinthorsdottir, V.; Sun, L.; Takeuchi, F.; Tallapragada, D.S.P.; Taylor, K.D.; Tayo, B.O.; Tcheandjieu, C.; Terzikhan, N.; Tesolin, P.; Teumer, A.; Theusch, E.; Thompson, D.J.; Thorleifsson, G.; Timmers, P.R.H.J.; Trompet, S.; Turman, C.; Vaccargiu, S.; van der Laan, S.W.; van der Most, P.J.; van Klinken, J.B.; van Setten, J.; Verma, S.S.; Verweij, N.; Veturi, Y.; Wang, C.A.; Wang, C.; Wang, L.; Wang, Z.; Warren, H.R.; Bin Wei, W.; Wickremasinghe, A.R.; Wielscher, M.; Wiggins, K.L.; Winsvold, B.S.; Wong, A.; Wu, Y.; Wuttke, M.; Xia, R.; Xie, T.; Yamamoto, K.; Yang, J.; Yao, J.; Young, H.; Yousri, N.A.; Yu, L.; Zeng, L.; Zhang, W.; Zhang, X.; Zhao, J.H.; Zhao. W.; Zhou, W.; Zimmermann, M.E.; Zoledziewska, M.; Adair, L.S.; Adams, H.H.H.; Aguilar-Salinas, C.A.; Al-Mulla, F.; Arnett, D.K.; Arnett, D.K.; Asselbergs, F.W.; Åsvold, B.O.; Attia, J.; Banas, B.; Bandinelli, S.; Bennett D.A.; Bergler, T.; Bharadwaj, D.; Biino, G.; Bisgaard, H.; Boerwinkle, E.; Böger, C.A.; Bønnelykke, K.; Boomsma, D.I.; Børglum, A.D.; Borja, J.B.; Bouchard, C.; Bowden, D.W.; Brandslund, I.; Brumpton, B.; Buring, J.E.; Caulfield, M.J.; Chambers, J.C.; Chandak, G.R.; Chanock, S.J.; Chaturvedi, N.; Chen, Y.I.; Chen, Z.; Cheng, C.Y.; Christophersen, I.E.; Ciullo, M.; Cole, J.W.; Collins, F.S.; Cooper, R.S.; Cruz, M.; Cucca, F.; Cupples, L.A.; Cutler, M.J.; Damrauer, S.M.; Dantoft, T.M.; de Borst, G.J.; de Groot, L.C.P.G.M.; de Jager, P.L.; de Kleijn, D.P.V.; de Silva, H.J.; Dedoussis, G.V.; den Hollander, A.I.; Du, S.; Easton, D.F.; Elders, P.J.M.; Eliassen, A.H.; Ellinor, P.T.; Elmståhl, S.; Erdmann, J.; Evans, M.K.; Fatkin, D.; Feenstra, B.; Feitosa, M.F.; Ferrucci, L.; Ford, I.; Fornage, M.; Franke, A.; Franks, P.W.; Freedman, B.I.; Gasparini, P.; Gieger, C.; Girotto, G.; Goddard, M.E.; Golightly, Y.M.; Gonzalez-Villalpando. C.; Gordon-Larsen, P.; Grallert, H.; Grant, S.F.A.; Grarup, N.; Griffiths, L.; Gudnason, V.; Haiman, C.; Hakonarson, H.; Hansen, T.; Hartman, C.A.; Hattersley, A.T.; Hayward, C.; Heckbert, S.R.; Heng, C.K.; Hengstenberg, C.; Hewitt, A.W.; Hishigaki, H.; Hoyng, C.B.; Huang, P.L.; Huang, W.; Hunt, S.C.; Hveem, K.; Hyppönen, E.; Iacono, W.G.; Ichihara, S.; Ikram, M.A.; Isasi, C.R.; Jackson, R.D.; Jarvelin, M.R.; Jin, Z.B.; Jöckel, K.H.; Joshi, P.K.; Jousilahti, P.; Jukema, J.W.; Kähönen, M.; Kamatani, Y.; Kang, K.D.; Kaprio, J.; Kardia, S.L.R.; Karpe, F.; Kato, N.; Kee, F.; Kessler, T.; Khera, A.V.; Khor, C.C.; Kiemeney, L.A.L.M.; Kim, B.J.; Kim, E.K.; Kim, H.L.; Kirchhof, P.; Kivimaki, M.; Koh, W.P.; Koistinen, H.A.; Kolovou, G.D.; Kooner, J.S.; Kooperberg, C.; Köttgen, A.; Kovacs, P.; Kraaijeveld, A.; Kraft, P.; Krauss, R.M.; Kumari, M.; Kutalik, Z.; Laakso, M.; Lange, L.A.; Langenberg, C.; Launer, L.J.; Le Marchand, L.; Lee, H.; Lee, N.R.; Lehtimäki, T.; Li, H.; Li, L.; Lieb, W.; Lin, X.; Lind, L.; Linneberg, A.; Liu, C.T.; Liu, J.; Loeffler, M.; London, B.; Lubitz, S.A.; Lye, S.J.; Mackey, D.A.; Mägi, R.; Magnusson, P.K.E.; Marcus, G.M.; Vidal, P.M.; Martin, N.G.; Martin, N.G.; Lieb, W.; Lin, X.; Lind, L.; Linneberg, A.; Liu, C.T.; Liu, J.; Loeffler, M.; London, B.; Lubitz, S.A.; Lye, S.J.; Mackey, D.A.; Mägi, R.; Mägi, R.; Magnusson, P.K.E.; Marcus, G.M.; Vidal, P.M.; Martin, N.G.; März, W.; Matsuda, F.; McGarrah, R.W.; McGue, M.; McKnight, A.J.; Medland, S.E.; Mellström, D.; Metspalu, A.; Mitchell, B.D.; Mitchell, P.; Mook-Kanamori, D.O.; Morris, A.D.; Mucci, L.A.; Munroe, P.B.; Nalls, M.A.; Nazarian, S.; Nelson, A.E.; Neville, M.J.; Newton-Cheh, C.; Nielsen, C.S.; Nöthen, M.M.; Ohlsson, C.; Oldehinkel, A.J.; Oldehinkel, A.J.; Orozco, L.; Pahkala, K.; Pajukanta, P.; Palmer, C.N.A.; Parra, E.J.; Pattaro, C.; Pedersen, O.; Pennell, C.E.; Penninx, B.W.J.H.; Perusse, L.; Peters, A.; Peyser, P.A.; Porteous, D.J.; Posthuma, D.; Power, C.; Pramstaller, P.P.; Province, M.A.; Qi, Q.; Qu, J.; Rader, D.J.; Raitakari, O.T.; Ralhan, S.; Rallidis, L.S.; Rao, D.C.; Redline, S.; Reilly, D.F.; Reiner, A.P.; Rhee, S.Y.; Ridker, P.M.; Rienstra, M.; Ripatti, S.; Ritchie, M.D.; Roden, D.M.; Rosendaal, F.R.; Rotter, J.I.; Rudan, I.; Rutters, F.; Sabanayagam, C.; Saleheen, D.; Salomaa, V.; Samani, N.J.; Sanghera, D.K.; Sattar, N.; Schmidt, B.; Schmidt, H.; Schmidt, R.; Schulze, M.B.; Schunkert, H.; Scott, L.J.; Scott, R.J.; Sever, P.; Shiroma, E.J.; Shoemaker, M.B.; Shu, X.O.; Simonsick, E.M.; Sims, M.; Singh, J.R.; Singleton, A.B.; Sinner, M.F.; Smith, J.G.; Snieder, H.; Spector, T.D.; Stampfer, M.J.; Stark, K.J.; Strachan, D.P.; 't Hart, L.M.; Tabara, Y.; Tang, H.; Tardif, J.C.; Thanaraj, T.A.; Timpson, N.J.; Tönjes, A.; Tremblay, A.; Tuomi, T.; Tuomilehto, J.; Tusié-Luna, M.T.; Uitterlinden, A.G.; van Dam, R.M.; van der Harst, P.; Van der Velde, N.; van Duijn, C.M.; van Schoor, N.M.; Vitart, V.; Völker, U.; Vollenweider, P.; Völzke, H.; Wacher-Rodarte, N.H.; Walker, M.; Wang, Y.X.; Wareham, N.J.; Watanabe, R.M.; Watkins, H.; Weir, D.R.; Werge, T.M.; Widen, E.; Wilkens, L.R.; Willemsen, G.; Willett, W.C.; Wilson, J.F.; Wong, T.Y.; Woo, J.T.; Wright, A.F.; Wu, J.Y.; Xu, H.; Yajnik, C.S.; Yokota, M.; Yuan, J.M.; Zeggini, E.; Zemel, B.S.; Zheng, W.; Zhu, X.; Zmuda, J.M.; Zonderman, A.B.; Zwart, J.A.; 23andMe Research Team; VA Million Veteran Program.; DiscovEHR (DiscovEHR and MyCode Community Health Initiative).; eMERGE (Electronic Medical Records and Genomics Network).; Lifelines Cohort Study.; PRACTICAL Consortium.; Understanding Society Scientific Group.; Chasman, D.I.; Cho, Y.S.; Heid, I.M.; McCarthy, M.I.; Ng, M.C.Y.; O'Donnell, C.J.; Rivadeneira, F.; Thorsteinsdottir, U.; Sun, Y.V.; Tai, E.S.; Boehnke, M.; Deloukas, P.; Justice, A.E.; Lindgren, C.M.; Loos, R.J.F.; Mohlke, K.L.; North, K.E.; Stefansson, K.; Walters R.G.v.; Winkler, T.W.; Young, K.L.; Loh, P.R.; Yang, J.; Esko, T.; Assimes, T.L.; Auton, A.; Abecasis, G.R.; Willer, C.J.; Locke, A.E.; Berndt, S.I.; Lettre, G.; Frayling, T.M.; Frayling, T.M.; Okada, Y.; Wood, A.R.; Visscher, P.M.; Hirschhorn, J.N.Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.Item Alcohol use and alcoholic fatty liver disease: a prospective, communitybased study among adults in an urban community in Sri Lanka(The Sri Lanka Medical Association, 2022) Niriella, M.A.; Kasturiratne, A.; Beddage, T.; de Silva, S.T.; Dassanayake, A.S.; Pathmeswaran, A.; Wickremasinghe, A.R.; Kato, N.; de Silva, H.J.Background: Data on alcoholic fatty liver (AFL) is limited. Therefore, we investigated alcohol use and AFL in a cohort of adults in an urban community in Sri Lanka. Methods: The study population (selected by age-stratified random sampling) was screened in 2007 (35-64 years) and re-evaluated in 2014. They were assessed by structured interviews, anthropometric measurements, liver-ultrasound, and biochemical and serological tests. AFL was diagnosed on ultrasound criteria, ‘unsafe’ alcohol consumption (Asian standards: males>14 units, females >7 units per week) and absence of hepatitis B/C markers. Controls were unsafe alcohol consumers who had no fatty liver on ultrasound. Results: 2985/3012 (99%) had complete data for analysis. 272/2985 (9.1%) were unsafe-drinkers in 2007 [males-270; mean-age-51.9, SD-8.0 years]. 86/272 (31.6%) had AFL [males-85; mean-age-50.2, SD-8.6 years]. Male gender [p<0.001], increased waist circumference (WC) [OR 4.9, p<0.01], BMI>23kg/m2 [OR 3.5, p<0.01] and raised alanine aminotransferase (ALT) [OR 2.8, p<0.01] were independently associated with AFL. 173/272 (63.6%) unsafe alcohol consumers from 2007 were re-evaluated in 2014. 134/173 had either had AFL or had changed to ‘safe’ or no alcohol consumption. 21/39 (53.8%) [males-21 (100%), meanage- 57.9, SD-7.9 years] who remained ‘unsafe’ alcohol users who had no fatty liver in 2007 developed AFL after 7-years (annual incidence 7.7%). On bivariate analysis, only male gender was associated with new-onset AFL. Of the 42 who had AFL at baseline but changed their drinking status from unsafe to safe or no alcohol, 6 had resolution of fatty liver in 2014. Conclusion: In this community-based study among adults from an urban community, unsafe alcohol use was found in 9.1%. Among unsafe alcohol users, the prevalence of AFL was 31.6% and the annual incidence of AFL was 7.7%. New-onset AFL was independently associated with male gender.Item The iHealth-T2D study: a cluster randomised trial for the prevention of type 2 diabetes amongst South Asians with central obesity and prediabetes-a statistical analysis plan(BioMed Central, London, 2022) Muilwijk, M.; Loh, M.; Mahmood, S.; Palaniswamy, S.; Siddiqui, S.; Silva, W.; Frost, G.S.; Gage, H.M.; Jarvelin, M.R.; Rannan-Eliya, R.P.; Ahmad, S.; Jha, S.; Kasturiratne, A.; Katulanda, P.; Khawaja, K.I.; Kooner, J.S.; Wickremasinghe, A.R.; van Valkengoed, I.G.M.; Chambers, J.C.Background: South Asians are at high risk of type 2 diabetes (T2D). Lifestyle modification is effective at preventing T2D amongst South Asians, but the approaches to screening and intervention are limited by high costs, poor scalability and thus low impact on T2D burden. An intensive family-based lifestyle modification programme for the prevention of T2D was developed. The aim of the iHealth-T2D trial is to compare the effectiveness of this programme with usual care. Methods: The iHealth-T2D trial is designed as a cluster randomised controlled trial (RCT) conducted at 120 sites across India, Pakistan, Sri Lanka and the UK. A total of 3682 South Asian men and women with age between 40 and 70 years without T2D but at elevated risk for T2D [defined by central obesity (waist circumference ≥ 95 cm in Sri Lanka or ≥ 100 cm in India, Pakistan and the UK) and/or prediabetes (HbA1c ≥ 6.0%)] were included in the trial. Here, we describe in detail the statistical analysis plan (SAP), which was finalised before outcomes were available to the investigators. The primary outcome will be evaluated after 3 years of follow-up after enrolment to the study and is defined as T2D incidence in the intervention arm compared to usual care. Secondary outcomes are evaluated both after 1 and 3 years of follow-up and include biochemical measurements, anthropometric measurements, behavioural components and treatment compliance. Discussion: The iHealth-T2D trial will provide evidence of whether an intensive family-based lifestyle modification programme for South Asians who are at high risk for T2D is effective in the prevention of T2D. The data from the trial will be analysed according to this pre-specified SAP. Ethics and dissemination: The trial was approved by the international review board of each participating study site. Study findings will be disseminated through peer-reviewed publications and in conference presentations.Item Composite carotid intima-media thickness as a risk predictor of coronary heart disease in a selected population in Sri Lanka(Public Library of Science,, 2022) Abeysuriya, V.; Wijesinha, N.A.I.; Priyadharshan, P.P.; Chandrasena, L.G.; Wickremasinghe, A.R.Background: Segment-specific variations of carotid intima-media thickness (CIMT) have not been assessed in South Asian populations. The purpose of this study was to determine if segment-specific CIMTs or a composite-CIMT score is a better risk predictor of coronary heart disease in South Asian populations. Methods: A comparative prospective study was conducted from November 2019 to October 2020 in a hospital in Colombo, Sri Lanka. Based on pre-defined inclusion and exclusion criteria, cases (having a diagnosis of Coronary Heart Disease (CHD), n = 338) and controls (non-CHD group, n = 356) were recruited. Ultrasound examination of the common carotid (CCA), the carotid bulb (CB) and the internal carotid segments (ICA) of the carotid vessels was conducted by a radiologist, and CIMTs were measured. A composite-CIMT score defined as the average value of all six segments of the left and right sides was derived. Results: 694 participants were enrolled (male n = 399, 57.5%). The mean (±SD) age of the study sample was 60.2 (±9.86) years. There were variations in segment-specific values between the left and right vessels. The mean composite-CIMT value of the CHD group was significantly higher than that of the non-CHD group. A composite-CIMT score of 0.758 had a sensitivity of 98.4% and a specificity of 64.6% in distinguishing CHD from non-CHD groups (Area under the curve (AUC): 0.926). Conclusions: Carotid artery segment-specific CIMT variations were present in this population. The composite CIMT score is better than segment-specific CIMTs in predicting CHD and may be used to predict CHD in this population.