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2. Regional variation in characteristics of patients with decompensated cirrhosis admitted to hospitals in the UK

Author

Tavabie, Oliver D, primary, Abeysekera, Kushala WM, additional, Brennan, Paul N, additional, Marjot, Thomas, additional, Kronsten, Victoria T, additional, Li, Wenhao, additional, Nayagam, Jeremy S, additional, Dhaliwal, Amritpal, additional, Hardy, Tim, additional, Maurice, James B, additional, Zakeri, Nekisa, additional, Abbas, Nadir, additional, Abbasi, Abdullah, additional, Abbott, Jane, additional, Abdul, Rahman, additional, Abdulaziz, Mohamed, additional, Abduljabbar, Duaa, additional, Adamson, Robbie, additional, Adebayo, Danielle, additional, Adhikarla, Aditya Kumar, additional, Adler, Maciej, additional, Afifi, Mostafa, additional, Ahmad, Salman, additional, Ahmed, Shayan, additional, Aithal, Guruprasad, additional, Akram, Ali, additional, Al Radhi, Balqees, additional, Al-Talib, Ismaeel, additional, Alele, Jolomi, additional, Ali, Alaa Mohammed, additional, Almusai, Safa, additional, Appleby, Victoria, additional, Asmat, Huma, additional, Astbury, Sarah, additional, Atkinson, Ali, additional, Badrulhisham, Fakhirah, additional, Balachandrakumar, Vinay K, additional, Ball, Alexandra, additional, Banfa, Moses, additional, Barn, Jeevan, additional, Begum, Shahnaz, additional, Belfield, Katherine, additional, Bendall, Oliver, additional, Bennett, Kris, additional, Bernal, William, additional, Bhandari, Rajan, additional, Bhatti, Prashan, additional, Bradley, Meg, additional, Brown, Edward, additional, Bryce, Kathleen, additional, Buchanan, Ryan, additional, Burke, Laura, additional, Campbell, Roisin, additional, Cargill, Tamsin, additional, Carroll, Geraldine, additional, Cartledge, James, additional, Chatterjee, Devnandan, additional, Chaundry, Rayan, additional, Choudhry, Zeshan, additional, Clare, Kathleen, additional, Cobbold, Jeremy, additional, Coburn, Robert, additional, Cook, Charlotte, additional, Corvan, Fintan, additional, Cox, Rebecca, additional, Craig, Darren, additional, Creamer, John, additional, Curran, Christopher, additional, De Silva, Shanika, additional, Dean, Laurence, additional, Dillon, Jayne, additional, Dillon, John, additional, Dunn, Rebecca, additional, Eckersley, Robert, additional, Eike, Gidveig, additional, Elagib, Amul, additional, Elkholi, Ayman, additional, Elshaarawy, Omar, additional, Faloon, Sarah, additional, Fan, Francis, additional, Fazili, Mohammad, additional, Fernandes, Denzil, additional, Fox, James, additional, Foxton, Matthew, additional, Gaba, Waqas, additional, Gaikwad, Girish, additional, Gairola, Abishek, additional, Galanakis, Vasileios, additional, Gallaher, Charles, additional, Gautam, Nisham, additional, Germain, Lewis, additional, Giles, Ben, additional, Gill, Ceri, additional, Glover, Ben, additional, Glover, John, additional, Gomez, David, additional, Gomez, Michael, additional, Gordon, Victoria, additional, Gormley, Sarah, additional, Goulder, John, additional, Goyal, Simran, additional, Greenham, Olivia, additional, Guthrie, Sarah, additional, Hackett, Richard, additional, Haddadin, Yazan, additional, Hadjinicolaou, Andreas, additional, Hall, Jonathan, additional, Hamza, Mohammed, additional, Haque, Tasnuma, additional, Harris, Rebecca, additional, Hart, Catherine, additional, Hasan, Sundas, additional, Hasnain Nadir, Syed Mujtaba, additional, Hassall, James, additional, Hawker-Bond, George, additional, Hawkyard, Jake, additional, Healey, Scott, additional, Hogan, Brian, additional, Hornby, Catherine, additional, Humayun, MD, additional, Hutchison, John, additional, Iftikhar, Zahra, additional, Ismail, Asem, additional, James, Joel, additional, Jones, Rebecca, additional, Jopson, Laura, additional, Juthani, Dipal, additional, Kaina, Philippa, additional, Karim, Aadil, additional, Karim, Syed Misbah, additional, Kashyap, Vaishnavi, additional, Kassab, Mohamed, additional, Katarey, Dev, additional, Kenny, Lee, additional, Kerry, Georgina, additional, Khan, Adnan, additional, Khan, Ayesha, additional, Khan, Azab, additional, Khan, Muhammad Taha, additional, Khan, Tahir, additional, Khatib, Aseil, additional, Khattak, Mohammad Fawad, additional, King, Ji Jade, additional, Kooner, Emily, additional, Korani, Mohammed, additional, Kotha, Sreelakshmi, additional, Lam, Wai Liam, additional, Lateef, Mohammed, additional, Leighton, Jess, additional, Leith, Damien, additional, Liaros, Angela, additional, Liu Yin, James, additional, Lourenco, Floyd, additional, Lyles, Annabel, additional, Macken, Lucia, additional, Magee, Ciaran, additional, Maggs, Daniel, additional, Mahalingam, Aarani, additional, Mahenthiran, Midusa, additional, Mahmood, Rizwan, additional, Mandour, Mandour Omer, additional, Manocha, Namita, additional, Mansour, Dina, additional, Marks, Daniella, additional, Martin, Ciara, additional, Martin, Harry, additional, Martin, Iana, additional, Martin, Katherine, additional, Maruthan, Sachan, additional, Masin, Rhys, additional, Mason, Denise, additional, Matthews, Charmaine, additional, Mavrou, Athina, additional, Maxan, Ema, additional, Maxfield, Dominic, additional, McAvoy, Emma, additional, McCaughan, Hannah, additional, McColl, Kirsty, additional, McCorry, Roger, additional, McDonald, Stewart, additional, McDowell, Hannah, additional, McGoran, John, additional, McIlwane, Stewart, additional, McPherson, Stuart, additional, Meakin, Olivia, additional, Mebarek, Leila, additional, Merrill, Hannah, additional, Michail, Stephanie, additional, Modarres, Pedram, additional, Mohamedali, Alaa, additional, Mohammed, Yaser, additional, Mohammed, Zakiuddin, additional, Mohan, Jaiganesh, additional, Monnier, Chloe, additional, Moran, Eilis, additional, Moroni, Francesca, additional, Morrison, Gary, additional, Msaddi, Anas, additional, Mutar, Sarah, additional, Nahed, Ismail, additional, Navaratnam, Janardhan, additional, Neto-Pereira, Luis, additional, Ng, Jennifer, additional, Nwoguh, Chinonso, additional, O'Kane, Rebecca, additional, Omar, Sohail, additional, Ososanya, Abosede, additional, Parambil, Jessiya Veliyankodan, additional, Patel, Jay, additional, Pericleous, Marinos, additional, Pervais, Zeshan, additional, Phoolchund, Anju, additional, Pietrzycki, Julian, additional, Pillay, Lushen, additional, Pohl, Keith, additional, Prabhu, Kiran, additional, Putri, Yesita Rizky F., additional, Qazi, Umang, additional, Rafique, Khizar Khalid, additional, Raghuraman, Arun, additional, Raman, Krithivasan, additional, Ranade, Vaishali, additional, Rastelli, Francesca, additional, Ratcliffe, Elizabeth, additional, Rattehalli, Deepa, additional, Raza, Tufail, additional, Razak, Amir, additional, Read, George, additional, Robins, Anne, additional, Rowe, Ian, additional, Rushbrook, Simon, additional, Salama, Mohamed, additional, Saravan, Ramasamy, additional, Sarkar, Srishti, additional, Saunsbury, Emma, additional, Scott, Jennifer, additional, Serna, Solange, additional, Shahzad, Hassnain, additional, Shamsaldeen, Mohammed, additional, Sharip, Mohammed, additional, Shearer, Jessica, additional, Sheikh, Adam, additional, Sheiybani, Giovanna, additional, Sherwin, Michelle, additional, Sheth, Abhishek, additional, Shintre, Nidhi, additional, Singhal, Saket, additional, Sinha, Rohit, additional, Sinharay, Ricky, additional, Smith, Gloria, additional, Smith, Ria, additional, Snowdon, Victoria, additional, Spicer, Joanne, additional, Spoor, Johannes, additional, Sreenivasan, Shiva, additional, Srinivasa, Amar, additional, Srivastava, Ankur, additional, St. Aimee, Louise, additional, Stagg, Georgia, additional, Stanley, Jatinder, additional, Stevenson, Jason, additional, Stokes, Daniel, additional, Stroud, Robert, additional, Subhani, Mohsan, additional, Suliman, Hiba, additional, Sultana, Marium, additional, Summers, Nikki, additional, Sutherland, Chloe, additional, Swann, Rachael, additional, Sykes, Lynne, additional, Taha, Mostafa, additional, Tan, Kwei Eng, additional, Tariq, Zohaib, additional, Tay, Joshua Jun Ming, additional, Taylor, Alison, additional, Thakor, Amit, additional, Tsang, James, additional, Turner, Lucy, additional, Tyler, Zaccharie, additional, Unitt, Esther, additional, Volcek, Edward, additional, Watson, Iona, additional, Watters, Chris, additional, Wells, Gemma, additional, White, Helen, additional, Widlak, Monika, additional, Williams, Matthew, additional, Wischhusen, Jack, additional, Woodland, Hazel, additional, Wren, Louise, additional, Xyda, Souzana, additional, Yeh, Julian, additional, Young, Alison, additional, and Yuan, Jack Shie Jie, additional

Published
2023
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3. Defining characteristics and outcomes for patients with non-alcoholic fatty liver disease admitted to hospital with decompensated cirrhosis

Author

Tavabie, Oliver D., Abbott, Jane, Abeysekera, Kushala WM., Balachandrakumar, Vinay K., Bennett, Kris, Brennan, Paul, Buchanan, Ryan, Dhaliwal, Amritpal, Galanakis, Vasileios, Hardy, Tim, Harris, Rebecca, Kronsten, Victoria T., Leighton, Jess, Li, Wenhao, Yin, James Liu, Macken, Lucia, Marjot, Thomas, Maurice, James B., McDowell, Hannah, Navaratnam, Janardhan, Pohl, Keith, Nayagam, Jeremy S., Saunsbury, Emma, Scott, Jennifer, Sheth, Abhishek, Sinharay, Ricky, Sheiybani, Giovanna, Subhani, Mohsan, Turner, Lucy, White, Helen, Zakeri, Nekisa, Cook, Charlotte, Abbas, Nadir, Abbasi, Abdullah, Abdul, Rahman, Abdulaziz, Mohamed, Abduljabbar, Duaa, Adamson, Robbie, Adebayo, Danielle, Adhikarla, Aditya Kumar, Adler, Maciej, Ahmad, Salman, Ahmed, Shayan, Afifi, Mostafa, Akram, Ali, Al Radhi, Balqees, Al-Talib, Ismaeel, Alele, Jolomi, Ali, Alaa Mohammed, Almusai, Safa, Appleby, Victoria, Asmat, Huma, Astbury, Sarah, Atkinson, Ali, Badrulhisham, Fakhirah, Ball, Alexandra, Banfa, Moses, Barn, Jeevan, Begum, Shahnaz, Belfield, Katherine, Bendall, Oliver, Bhandari, Rajan, Bhatti, Prashan, Bradley, Meg, Brown, Edward, Bryce, Kathleen, Burke, Laura, Campbell, Roisin, Cargill, Tamsin, Carroll, Geraldine, Cartledge, James, Chatterjee, Devnandan, Chaundry, Rayan, Choudhry, Zeshan, Clare, Kathleen, Cobbold, Jeremy, Coburn, Robert, Corvan, Fintan, Cox, Rebecca, Craig, Darren, Creamer, John, Curran, Christopher, De Silva, Shanika, Dean, Laurence, Dillon, Jayne, Dunn, Rebecca, Eckersley, Robert, Eike, Gidveig, Elagib, Amul, Elkholi, Ayman, Elshaarawy, Omar, Faloon, Sarah, Fan, Francis, Fazili, Mohammad, Fernandes, Denzil, Fox, James, Foxton, Matthew, Gaba, Waqas, Gaikwad, Girish, Gairola, Abishek, Gallaher, Charles, Gautam, Nisham, Germain, Lewis, Giles, Ben, Gill, Ceri, Glover, Ben, Glover, John, Gomez, David, Gomez, Michael, Gordon, Victoria, Gormley, Sarah, Goulder, John, Goyal, Simran, Greenham, Olivia, Guthrie, Sarah, Hackett, Richard, Haddadin, Yazan, Hadjinicolaou, Andreas, Hall, Jonathan, Haque, Tasnuma, Hart, Catherine, Hasnain Nadir, Syed Mujtaba, Hassall, James, Hasan, Sundas, Hawker-Bond, George, Hawkyard, Jake, Healey, Scott, Hornby, Catherine, Hamza, Mohammed, Humayun, M.D., Hutchison, John, Iftikhar, Zahra, Ismail, Asem, James, Joel, Jopson, Laura, Juthani, Dipal, Kaina, Philippa, Karim, Aadil, Karim, Syed Misbah, Kashyap, Vaishnavi, Kassab, Mohamed, Katarey, Dev, Kenny, Lee, Kerry, Georgina, Khan, Adnan, Khan, Ayesha, Khan, Azab, Khan, Muhammad Taha, Khan, Tahir, Khatib, Aseil, Khattak, Mohammad Fawad, King, Ji Jade, Korani, Mohammed, Kotha, Sreelakshmi, Kooner, Emily, Lam, Wai Liam, Lateef, Mohammed, Leith, Damien, Liaros, Angela, Lourenco, Floyd, Lyles, Annabel, Mahenthiran, Midusa, Magee, Ciaran, Maggs, Daniel, Mahalingam, Aarani, Mahmood, Rizwan, Mandour, Mandour Omer, Manocha, Namita, Mansour, Dina, Marks, Daniella, Martin, Ciara, Martin, Harry, Martin, Iana, Martin, Katherine, Maruthan, Sachan, Masin, Rhys, Mason, Denise, Matthews, Charmaine, Mavrou, Athina, Maxan, Ema, Maxfield, Dominic, McAvoy, Emma, McColl, Kirsty, McCaughan, Hannah, McCorry, Roger, McGoran, John, McDonald, Stewart, McIlwane, Stewart, Meakin, Olivia, Mebarek, Leila, Merrill, Hannah, Michail, Stephanie, Modarres, Pedram, Mohamedali, Alaa, Mohammed, Yaser, Mohammed, Zakiuddin, Mohan, Jaiganesh, Monnier, Chloe, Moran, Eilis, Morrison, Gary, Moroni, Francesca, Msaddi, Anas, Mutar, Sarah, Neto-Pereira, Luis, Nahed, Ismail, Ng, Jennifer, Nwoguh, Chinonso, O’Kane, Rebecca, Omar, Sohail, Ososanya, Abosede, Parambil, Jessiya Veliyankodan, Patel, Jay, Pericleous, Marinos, Pervais, Zeshan, Phoolchund, Anju, Pietrzycki, Julian, Pillay, Lushen, Prabhu, Kiran, Putri, Yesita Rizky F., Qazi, Umang, Rafique, Khizar Khalid, Raman, Krithivasan, Ranade, Vaishali, Rastelli, Francesca, Ratcliffe, Elizabeth, Rattehalli, Deepa, Raza, Tufail, Razak, Amir, Raghuraman, Arun, Read, George, Robins, Anne, Rushbrook, Simon, Salama, Mohamed, St. Aimee, Louise, Saravan, Ramasamy, Sarkar, Srishti, Serna, Solange, Shahzad, Hassnain, Shamsaldeen, Mohammed, Sharip, Mohammed, Shearer, Jessica, Sheikh, Adam, Sherwin, Michelle, Shintre, Nidhi, Singhal, Saket, Sinha, Rohit, Smith, Gloria, Smith, Ria, Spicer, Joanne, Spoor, Johannes, Sreenivasan, Shiva, Srinivasa, Amar, Srivastava, Ankur, Stagg, Georgia, Stanley, Jatinder, Stevenson, Jason, Stokes, Daniel, Stroud, Robert, Suliman, Hiba, Sultana, Marium, Summers, Nikki, Sutherland, Chloe, Swann, Rachael, Sykes, Lynne, Taha, Mostafa, Tan, Kwei Eng, Tariq, Zohaib, Ming Tay, Joshua Jun, Taylor, Alison, Thakor, Amit, Tsang, James, Tyler, Zaccharie, Unitt, Esther, Volcek, Edward, Wischhusen, Jack, Watson, Iona, Watters, Chris, Wells, Gemma, Widlak, Monika, Williams, Matthew, Woodland, Hazel, Wren, Louise, Xyda, Souzana, Yeh, Julian, Young, Alison, Jie Yuan, Jack Shie, Aithal, Guruprasad, Bernal, William, Dillon, John, Hogan, Brian, McPherson, Stuart, Jones, Rebecca, Rowe, Ian, and Snowdon, Victoria

Published
2023
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7. rs641738C>T near MBOAT7 is associated with liver fat, ALT and fibrosis in NAFLD: A meta-analysis

Author

Teo, Kevin, Abeysekera, Kushala WM, Adams, Leon, Aigner, Elmar, Anstee, Quentin M, Banales, Jesus M, Banerjee, Rajarshi, Basu, Priyadarshi, Berg, Thomas, Bhatnagar, Pallav, Buch, Stephan, Canbay, Ali, Caprio, Sonia, Chatterjee, Ankita, Ida Chen, Yii-Der, Chowdhury, Abhijit, Daly, Ann K, Datz, Christian, de Gracia Hahn, Dana, DiStefano, Johanna K, Dong, Jiawen, Duret, Amedine, EU-PNAFLD Investigators, Emdin, Connor, Fairey, Madison, Gerhard, Glenn S, GOLD Consortium, Guo, Xiuqing, Hampe, Jochen, Hickman, Matthew, Heintz, Lena, Hudert, Christian, Hunter, Harriet, Kelly, Matt, Kozlitina, Julia, Krawczyk, Marcin, Lammert, Frank, Langenberg, Claudia, Lavine, Joel, Li, Lin, Lim, Hong Kai, Loomba, Rohit, Luukkonen, Panu K, Melton, Phillip E, Mori, Trevor A, Palmer, Nicholette D, Parisinos, Constantinos A, Pillai, Sreekumar G, Qayyum, Faiza, Reichert, Matthias C, Romeo, Stefano, Rotter, Jerome I, Im, Yu Ri, Santoro, Nicola, Schafmayer, Clemens, Speliotes, Elizabeth K, Stender, Stefan, Stickel, Felix, Still, Christopher D, Strnad, Pavel, Taylor, Kent D, Tybjærg-Hansen, Anne, Umano, Giuseppina Rosaria, Utukuri, Mrudula, Valenti, Luca, Wagenknecht, Lynne E, Wareham, Nicholas J, Watanabe, Richard M, Wattacheril, Julia, Yaghootkar, Hanieh, Yki-Järvinen, Hannele, Young, Kendra A, Mann, Jake P, Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nicholas [0000-0003-1422-2993], Mann, Jake [0000-0002-4711-9215], and Apollo - University of Cambridge Repository

Subjects
Liver Cirrhosis, Diabetes, Membrane Proteins, Alanine Transaminase, ALSPAC, Fibrosis, Triglyceride, Polymorphism, Single Nucleotide, MBOAT7, Liver, Non-alcoholic Fatty Liver Disease, NAFLD, Drug Discovery, Humans, Genetic Predisposition to Disease, Acyltransferases
Abstract

BACKGROUND & AIMS: A common genetic variant near MBOAT7 (rs641738C>T) has been previously associated with hepatic fat and advanced histology in NAFLD; however, these findings have not been consistently replicated in the literature. We aimed to establish whether rs641738C>T is a risk factor across the spectrum of NAFLD and to characterise its role in the regulation of related metabolic phenotypes through a meta-analysis. METHODS: We performed a meta-analysis of studies with data on the association between rs641738C>T genotype and liver fat, NAFLD histology, and serum alanine aminotransferase (ALT), lipids or insulin. These included directly genotyped studies and population-level data from genome-wide association studies (GWAS). We performed a random effects meta-analysis using recessive, additive and dominant genetic models. RESULTS: Data from 1,066,175 participants (9,688 with liver biopsies) across 42 studies were included in the meta-analysis. rs641738C>T was associated with higher liver fat on CT/MRI (+0.03 standard deviations [95% CI 0.02-0.05], pz = 4.8×10-5) and diagnosis of NAFLD (odds ratio [OR] 1.17 [95% CI 1.05-1.3], pz = 0.003) in Caucasian adults. The variant was also positively associated with presence of advanced fibrosis (OR 1.22 [95% CI 1.03-1.45], pz = 0.021) in Caucasian adults using a recessive model of inheritance (CC + CT vs. TT). Meta-analysis of data from previous GWAS found the variant to be associated with higher ALT (pz = 0.002) and lower serum triglycerides (pz = 1.5×10-4). rs641738C>T was not associated with fasting insulin and no effect was observed in children with NAFLD. CONCLUSIONS: Our study validates rs641738C>T near MBOAT7 as a risk factor for the presence and severity of NAFLD in individuals of European descent. LAY SUMMARY: Fatty liver disease is a common condition where fat builds up in the liver, which can cause liver inflammation and scarring (including 'cirrhosis'). It is closely linked to obesity and diabetes, but some genes are also thought to be important. We did this study to see whether one specific change ('variant') in one gene ('MBOAT7') was linked to fatty liver disease. We took data from over 40 published studies and found that this variant near MBOAT7 is linked to more severe fatty liver disease. This means that drugs designed to work on MBOAT7 could be useful for treating fatty liver disease.

Published
2021

8. rs641738C>T near MBOAT7 promotes steatosis, NASH, fibrosis and hepatocellular carcinoma in non-alcoholic fatty liver disease: a meta-analysis

Author

Teo, Kevin, Abeysekera, Kushala WM, Adams, Leon, Aigner, Elmar, Banerjee, Rajarshi, Basu, Priyadarshi, Berg, Thomas, Bhatnagar, Pallav, Buch, Stephan, Canbay, Ali, Caprio, Sonia, Chatterjee, Ankita, Chen, Yii-Der Ida, Datz, Christian, de Gracia Hahn, Dana, DiStefano, Johanna K, Dong, Jiawen, Duret, Amedine, Emdin, Connor, Fairey, Madison, Gerhard, Glenn S, Guo, Xiuqing, Hampe, Jochen, Hickman, Matthew, Heintz, Lena, Hudert, Christian, Hunter, Harriet, Kelly, Matt, Kozlitina, Julia, Krawczyk, Marcin, Lammert, Frank, Langenberg, Claudia, Lavine, Joel, Lim, Hong Kai, Luukkonen, Panu, Melton, Philip E, Mori, Trevor A, Parisinos, Constantinos A, Pillai, Sreekumar G, Qayyum, Faiza, Reichert, Matthias C, Romeo, Stefano, Rotter, Jerome, Im, Yu Ri, Santoro, Nicola, Schafmayer, Clemens, Speliotes, Elizabeth K, Stender, Stefan, Stickel, Felix, Still, Christopher D, Strnad, Pavel, Taylor, Kent D, Tybjaerg-Hansen, Anne, Umano, Giuseppina Rosaria, Utukuri, Mrudula, Valenti, Luca, Wareham, Nicholas J, Wattacheril, Julia, Yki-Jarvinen, Hannele, and Mann, Jake P

Abstract

A common genetic variant near MBOAT7 (rs641738C>T) has been previously associated with hepatic fat and advanced histology in non-alcoholic fatty liver disease (NAFLD), however, these findings have not been consistently replicated in the literature. Therefore, we aimed to establish whether rs641738 is a risk factor for NAFLD through meta-analysis. Data from 134,015 participants (7,692 with liver biopsies and 50,680 with imaging) was included in the meta-analysis. The minor T-allele of rs641738C>T was associated with higher liver fat on CT/MRI using an additive genetic model (+0.05 standard deviations [95% CI: 0.01 - 0.09], p=0.025), and with an increased risk of NAFLD (per-allele OR: 1.08 [95% CI: 1.01 - 1.15]), nonalcoholic steatohepatitis (OR: 1.11 [95% CI: 1.02 - 1.21]), advanced fibrosis (OR: 1.14 [95% CI: 1.05 - 1.23]), and hepatocellular carcinoma (OR: 1.43 [95% CI: 1.22 - 1.67]) in adults with NAFLD. Sub-group analysis did not demonstrate a difference in Caucasians and non-Caucasians. Rs641738C>T was not associated with markers of insulin resistance but was associated with higher risk of stroke in the UK Biobank. These data validate rs641738C>T near MBOAT7 as a risk factor for the development, activity, and stage of NAFLD including hepatocellular carcinoma.

Published
2019
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11. rs641738C>T near MBOAT7 is associated with liver fat, ALT and fibrosis in NAFLD: A meta-analysis

Author

Teo, Kevin, Abeysekera, Kushala WM, Adams, Leon, Aigner, Elmar, Anstee, Quentin M, Banales, Jesus M, Banerjee, Rajarshi, Basu, Priyadarshi, Berg, Thomas, Bhatnagar, Pallav, Buch, Stephan, Canbay, Ali, Caprio, Sonia, Chatterjee, Ankita, Ida Chen, Yii-Der, Chowdhury, Abhijit, Daly, Ann K, Datz, Christian, De Gracia Hahn, Dana, DiStefano, Johanna K, Dong, Jiawen, Duret, Amedine, EU-PNAFLD Investigators, Emdin, Connor, Fairey, Madison, Gerhard, Glenn S, GOLD Consortium, Guo, Xiuqing, Hampe, Jochen, Hickman, Matthew, Heintz, Lena, Hudert, Christian, Hunter, Harriet, Kelly, Matt, Kozlitina, Julia, Krawczyk, Marcin, Lammert, Frank, Langenberg, Claudia, Lavine, Joel, Li, Lin, Lim, Hong Kai, Loomba, Rohit, Luukkonen, Panu K, Melton, Phillip E, Mori, Trevor A, Palmer, Nicholette D, Parisinos, Constantinos A, Pillai, Sreekumar G, Qayyum, Faiza, Reichert, Matthias C, Romeo, Stefano, Rotter, Jerome I, Im, Yu Ri, Santoro, Nicola, Schafmayer, Clemens, Speliotes, Elizabeth K, Stender, Stefan, Stickel, Felix, Still, Christopher D, Strnad, Pavel, Taylor, Kent D, Tybjærg-Hansen, Anne, Umano, Giuseppina Rosaria, Utukuri, Mrudula, Valenti, Luca, Wagenknecht, Lynne E, Wareham, Nicholas J, Watanabe, Richard M, Wattacheril, Julia, Yaghootkar, Hanieh, Yki-Järvinen, Hannele, Young, Kendra A, and Mann, Jake P

Subjects
Liver Cirrhosis, Diabetes, Membrane Proteins, Alanine Transaminase, ALSPAC, Fibrosis, Triglyceride, Polymorphism, Single Nucleotide, 3. Good health, MBOAT7, Liver, Non-alcoholic Fatty Liver Disease, NAFLD, Drug Discovery, Humans, Genetic Predisposition to Disease, Acyltransferases
Abstract

BACKGROUND & AIMS: A common genetic variant near MBOAT7 (rs641738C>T) has been previously associated with hepatic fat and advanced histology in NAFLD; however, these findings have not been consistently replicated in the literature. We aimed to establish whether rs641738C>T is a risk factor across the spectrum of NAFLD and to characterise its role in the regulation of related metabolic phenotypes through a meta-analysis. METHODS: We performed a meta-analysis of studies with data on the association between rs641738C>T genotype and liver fat, NAFLD histology, and serum alanine aminotransferase (ALT), lipids or insulin. These included directly genotyped studies and population-level data from genome-wide association studies (GWAS). We performed a random effects meta-analysis using recessive, additive and dominant genetic models. RESULTS: Data from 1,066,175 participants (9,688 with liver biopsies) across 42 studies were included in the meta-analysis. rs641738C>T was associated with higher liver fat on CT/MRI (+0.03 standard deviations [95% CI 0.02-0.05], pz = 4.8×10-5) and diagnosis of NAFLD (odds ratio [OR] 1.17 [95% CI 1.05-1.3], pz = 0.003) in Caucasian adults. The variant was also positively associated with presence of advanced fibrosis (OR 1.22 [95% CI 1.03-1.45], pz = 0.021) in Caucasian adults using a recessive model of inheritance (CC + CT vs. TT). Meta-analysis of data from previous GWAS found the variant to be associated with higher ALT (pz = 0.002) and lower serum triglycerides (pz = 1.5×10-4). rs641738C>T was not associated with fasting insulin and no effect was observed in children with NAFLD. CONCLUSIONS: Our study validates rs641738C>T near MBOAT7 as a risk factor for the presence and severity of NAFLD in individuals of European descent. LAY SUMMARY: Fatty liver disease is a common condition where fat builds up in the liver, which can cause liver inflammation and scarring (including 'cirrhosis'). It is closely linked to obesity and diabetes, but some genes are also thought to be important. We did this study to see whether one specific change ('variant') in one gene ('MBOAT7') was linked to fatty liver disease. We took data from over 40 published studies and found that this variant near MBOAT7 is linked to more severe fatty liver disease. This means that drugs designed to work on MBOAT7 could be useful for treating fatty liver disease.

12. Association of maternal pre-pregnancy BMI and breastfeeding with NAFLD in young adults: a parental negative control study.

Author

Abeysekera KW, Orr JG, Madley-Dowd P, Fernandes GS, Zuccolo L, Gordon FH, Lawlor DA, Heron J, and Hickman M

Abstract

Background: The importance of the maternal-infant dyad in the genesis of nonalcoholic fatty liver disease (NAFLD) is of increasing interest. The Avon Longitudinal Study of Parents and Children (ALSPAC) showed that at age 24, 1 in 5 had NAFLD measured by transient elastography and controlled attenuation parameter (CAP). Our aim was to investigate the association between breastfeeding duration and maternal pre-pregnancy BMI on offspring NAFLD in young adulthood., Methods: 4021 participants attended clinic for FibroScan and CAP measurement using Echosens 502 Touch®. 440 participants with Alcohol Use Disorders were excluded. Offspring of 100 non-singleton pregnancies were excluded. 2961 valid CAP measurements for NAFLD were analysed. Exposures of interest were breastfeeding of any duration, ≥6months exclusive breastfeeding, and maternal pre-pregnancy BMI. Multivariable regression models estimated the odds of NAFLD at 24 years. We performed a paternal negative control test to explore residual confounding in the analyses of pre-pregnancy BMI., Findings: There was a modest inverse association of exclusive and non-exclusive breastfeeding ≥6 months having a protective effect on NAFLD in offspring (OR 0·92 [95%CI 0·66-1·27] and OR 0·90 [0·67-1·21] respectively).The odds of offspring NAFLD in overweight pre-pregnancy maternal BMI and paternal BMI was OR 2·09 [1·62-2·68] and OR 1·33 [95%CI 1·07-1·65] respectively, with the ratio of effect sizes OR 1·57 [1·11-2·22]. Similarly, odds of offspring NAFLD with obese pre-pregnancy maternal BMI and paternal BMI was OR 2·66 [1·71-4·14] and OR 1·35 [0·91-2·00] respectively, with the ratio of effect sizes OR 1·98 [1·05-3·74]., Interpretation: Higher maternal pre-pregnancy BMI was associated with offspring NAFLD, having accounted for shared parental confounding. We did not replicate previous work that found a strong association between breastfeeding and NAFLD., Funding: Medical Research Council UK, Alcohol Research UK, David Telling Charitable Trust., Competing Interests: DAL has received support from Medtronic Ltd and Roche Diagnostics for research unrelated to that presented here. MH has received lecturer honoraria from MSD and Gilead. Other authors declared no conflicts of interest., (Crown Copyright © 2021 Published by Elsevier Ltd.)

Published
2021
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