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1. Genetic risk impacts the association of menopausal hormone therapy with colorectal cancer risk

Author

Tian, Yu, Lin, Yi, Qu, Conghui, Arndt, Volker, Baurley, James W., Berndt, Sonja I., Bien, Stephanie A., Bishop, D. Timothy, Brenner, Hermann, Buchanan, Daniel D., Budiarto, Arif, Campbell, Peter T., Carreras-Torres, Robert, Casey, Graham, Chan, Andrew T., Chen, Rui, Chen, Xuechen, Conti, David V., Díez-Obrero, Virginia, Dimou, Niki, Drew, David A., Figueiredo, Jane C., Gallinger, Steven, Giles, Graham G., Gruber, Stephen B., Gunter, Marc J., Harlid, Sophia, Harrison, Tabitha A., Hidaka, Akihisa, Hoffmeister, Michael, Huyghe, Jeroen R., Jenkins, Mark A., Jordahl, Kristina M., Joshi, Amit D., Keku, Temitope O., Kawaguchi, Eric, Kim, Andre E., Kundaje, Anshul, Larsson, Susanna C., Marchand, Loic Le, Lewinger, Juan Pablo, Li, Li, Moreno, Victor, Morrison, John, Murphy, Neil, Nan, Hongmei, Nassir, Rami, Newcomb, Polly A., Obón-Santacana, Mireia, Ogino, Shuji, Ose, Jennifer, Pardamean, Bens, Pellatt, Andrew J., Peoples, Anita R., Platz, Elizabeth A., Potter, John D., Prentice, Ross L., Rennert, Gad, Ruiz-Narvaez, Edward A., Sakoda, Lori C., Schoen, Robert E., Shcherbina, Anna, Stern, Mariana C., Su, Yu-Ru, Thibodeau, Stephen N., Thomas, Duncan C., Tsilidis, Konstantinos K., van Duijnhoven, Franzel J. B., Van Guelpen, Bethany, Visvanathan, Kala, White, Emily, Wolk, Alicja, Woods, Michael O., Wu, Anna H., Peters, Ulrike, Gauderman, W. James, Hsu, Li, and Chang-Claude, Jenny

Published
2024
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2. Gene-Environment Analyses Reveal Novel Genetic Candidates with Prenatal Tobacco Exposure in Relation to Risk for Childhood Acute Lymphoblastic Leukemia.

Author

Zhong, Charlie, Li, Shaobo, Arroyo, Katti, Morimoto, Libby M, de Smith, Adam J, Metayer, Catherine, Ma, Xiaomei, Kogan, Scott C, Gauderman, W James, and Wiemels, Joseph L

Subjects
Epidemiology, Biomedical and Clinical Sciences, Public Health, Health Sciences, Pediatric Research Initiative, Genetic Testing, Tobacco Smoke and Health, Genetics, Pediatric Cancer, Perinatal Period - Conditions Originating in Perinatal Period, Hematology, Childhood Leukemia, Rare Diseases, Tobacco, Cancer, Pediatric, Clinical Research, Prevention, 2.2 Factors relating to the physical environment, 2.1 Biological and endogenous factors, Aetiology, Reproductive health and childbirth, Good Health and Well Being, Infant, Newborn, Pregnancy, Female, Humans, Nicotiana, Maternal Exposure, Smoking, DNA Methylation, Transcription Factors, Tobacco Smoke Pollution, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Prenatal Exposure Delayed Effects, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundAssociations between maternal tobacco exposure during pregnancy and childhood acute lymphoblastic leukemia (ALL) have yielded mixed results. This may be due to biases in self-reported smoking or other differences in individual-level risk factors. We utilized a biological marker of maternal tobacco exposure to evaluate the association between maternal tobacco exposure during pregnancy, genetics, and subsequent childhood ALL risk in two large population-based studies of childhood ALL in California.MethodsMaternal exposure to tobacco smoke was assessed with a validated methylation marker (cg05575921) of the aryl hydrocarbon receptor repressor (AHRR) gene in newborn dried blood spots. We adjusted for sex, birthweight, gestational age, mode of delivery, year of birth, AHRR quantitative trait locus (mQTL) rs77111113, and a polygenetic risk score for childhood ALL. We additionally adjusted for principal components in a gene-environment interaction testing method that incorporates gene-only and environment-only effects along with interactions.ResultsAHRR hypomethylation overall was not associated with childhood ALL. In gene-environment interaction testing, several genetic variants displayed significant interaction with AHRR hypomethylation and childhood ALL.ConclusionsOur results suggest that novel candidates in PTPRK and DPP6 may play a role in tobacco-related leukemogenesis. Further research is necessary to better understand the effects of tobacco and these variants on childhood ALL risk.ImpactDespite the lack of an overall "main effect," tobacco exposure during pregnancy affects childhood ALL risk depending on specific genetic variants.

Published
2023

3. Children’s Health in London and Luton (CHILL) cohort: a 12-month natural experimental study of the effects of the Ultra Low Emission Zone on children’s travel to school

Author

Xiao, Christina, Scales, James, Chavda, Jasmine, Dove, Rosamund E., Tsocheva, Ivelina, Wood, Helen E., Kalsi, Harpal, Sartori, Luke, Colligan, Grainne, Moon, Jessica, Lie, Esther, Petrovic, Kristian, Day, Bill, Howett, Cheryll, Keighley, Amanda, Mihaylova, Borislava, Toffolutti, Veronica, Grigg, Jonathan, Randhawa, Gurch, Sheikh, Aziz, Fletcher, Monica, Mudway, Ian, Beevers, Sean, Gauderman, W. James, Griffiths, Christopher J., van Sluijs, Esther, and Panter, Jenna

Published
2024
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5. Author Correction: Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes

Author

Bradfeld, Jonathan P., Kember, Rachel L., Ulrich, Anna, Balkhiyarova, Zhanna, Alyass, Akram, Aris, Izzuddin M., Bell, Joshua A., Broadaway, K. Alaine, Chen, Zhanghua, Chai, Jin-Fang, Davies, Neil M., Fernandez-Orth, Dietmar, Bustamante, Mariona, Fore, Ruby, Ganguli, Amitavo, Heiskala, Anni, Hottenga, Jouke-Jan, Íñiguez, Carmen, Kobes, Sayuko, Leinonen, Jaakko, Lowry, Estelle, Lyytikainen, Leo-Pekka, Mahajan, Anubha, Pitkänen, Niina, Schnurr, Theresia M., Have, Christian Theil, Strachan, David P., Thiering, Elisabeth, Vogelezang, Suzanne, Wade, Kaitlin H., Wang, Carol A., Wong, Andrew, Holm, Louise Aas, Chesi, Alessandra, Choong, Catherine, Cruz, Miguel, Elliott, Paul, Franks, Steve, Frithiof-Bøjsøe, Christine, Gauderman, W. James, Glessner, Joseph T., Gilsanz, Vicente, Griesman, Kendra, Hanson, Robert L., Kaakinen, Marika, Kalkwarf, Heidi, Kelly, Andrea, Kindler, Joseph, Kähönen, Mika, Lanca, Carla, Lappe, Joan, Lee, Nanette R., McCormack, Shana, Mentch, Frank D., Mitchell, Jonathan A., Mononen, Nina, Niinikoski, Harri, Oken, Emily, Pahkala, Katja, Sim, Xueling, Teo, Yik-Ying, Baier, Leslie J., van Beijsterveldt, Toos, Adair, Linda S., Boomsma, Dorret I., de Geus, Eco, Guxens, Mònica, Eriksson, Johan G., Felix, Janine F., Gilliland, Frank D., Hansen, Torben, Hardy, Rebecca, Hivert, Marie-France, Holm, Jens-Christian, Jaddoe, Vincent W. V., Järvelin, Marjo-Riitta, Lehtimäki, Terho, Mackey, David A., Meyre, David, Mohlke, Karen L., Mykkänen, Juha, Oberfeld, Sharon, Pennell, Craig E., Perry, John R. B., Raitakari, Olli, Rivadeneira, Fernando, Saw, Seang-Mei, Sebert, Sylvain, Shepherd, John A., Standl, Marie, Sørensen, Thorkild I. A., Timpson, Nicholas J., Torrent, Maties, Willemsen, Gonneke, Hypponen, Elina, Power, Chris, McCarthy, Mark I., Freathy, Rachel M., Widén, Elisabeth, Hakonarson, Hakon, Prokopenko, Inga, Voight, Benjamin F., Zemel, Babette S., Grant, Struan F. A., and Cousminer, Diana L.

Published
2024
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6. Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes

Author

Chen, Zhishan, Guo, Xingyi, Tao, Ran, Huyghe, Jeroen R., Law, Philip J., Fernandez-Rozadilla, Ceres, Ping, Jie, Jia, Guochong, Long, Jirong, Li, Chao, Shen, Quanhu, Xie, Yuhan, Timofeeva, Maria N., Thomas, Minta, Schmit, Stephanie L., Díez-Obrero, Virginia, Devall, Matthew, Moratalla-Navarro, Ferran, Fernandez-Tajes, Juan, Palles, Claire, Sherwood, Kitty, Briggs, Sarah E. W., Svinti, Victoria, Donnelly, Kevin, Farrington, Susan M., Blackmur, James, Vaughan-Shaw, Peter G., Shu, Xiao-Ou, Lu, Yingchang, Broderick, Peter, Studd, James, Harrison, Tabitha A., Conti, David V., Schumacher, Fredrick R., Melas, Marilena, Rennert, Gad, Obón-Santacana, Mireia, Martín-Sánchez, Vicente, Oh, Jae Hwan, Kim, Jeongseon, Jee, Sun Ha, Jung, Keum Ji, Kweon, Sun-Seog, Shin, Min-Ho, Shin, Aesun, Ahn, Yoon-Ok, Kim, Dong-Hyun, Oze, Isao, Wen, Wanqing, Matsuo, Keitaro, Matsuda, Koichi, Tanikawa, Chizu, Ren, Zefang, Gao, Yu-Tang, Jia, Wei-Hua, Hopper, John L., Jenkins, Mark A., Win, Aung Ko, Pai, Rish K., Figueiredo, Jane C., Haile, Robert W., Gallinger, Steven, Woods, Michael O., Newcomb, Polly A., Duggan, David, Cheadle, Jeremy P., Kaplan, Richard, Kerr, Rachel, Kerr, David, Kirac, Iva, Böhm, Jan, Mecklin, Jukka-Pekka, Jousilahti, Pekka, Knekt, Paul, Aaltonen, Lauri A., Rissanen, Harri, Pukkala, Eero, Eriksson, Johan G., Cajuso, Tatiana, Hänninen, Ulrika, Kondelin, Johanna, Palin, Kimmo, Tanskanen, Tomas, Renkonen-Sinisalo, Laura, Männistö, Satu, Albanes, Demetrius, Weinstein, Stephanie J., Ruiz-Narvaez, Edward, Palmer, Julie R., Buchanan, Daniel D., Platz, Elizabeth A., Visvanathan, Kala, Ulrich, Cornelia M., Siegel, Erin, Brezina, Stefanie, Gsur, Andrea, Campbell, Peter T., Chang-Claude, Jenny, Hoffmeister, Michael, Brenner, Hermann, Slattery, Martha L., Potter, John D., Tsilidis, Kostas K., Schulze, Matthias B., Gunter, Marc J., Murphy, Neil, Castells, Antoni, Castellví-Bel, Sergi, Moreira, Leticia, Arndt, Volker, Shcherbina, Anna, Bishop, D. Timothy, Giles, Graham G., Southey, Melissa C., Idos, Gregory E., McDonnell, Kevin J., Abu-Ful, Zomoroda, Greenson, Joel K., Shulman, Katerina, Lejbkowicz, Flavio, Offit, Kenneth, Su, Yu-Ru, Steinfelder, Robert, Keku, Temitope O., van Guelpen, Bethany, Hudson, Thomas J., Hampel, Heather, Pearlman, Rachel, Berndt, Sonja I., Hayes, Richard B., Martinez, Marie Elena, Thomas, Sushma S., Pharoah, Paul D. P., Larsson, Susanna C., Yen, Yun, Lenz, Heinz-Josef, White, Emily, Li, Li, Doheny, Kimberly F., Pugh, Elizabeth, Shelford, Tameka, Chan, Andrew T., Cruz-Correa, Marcia, Lindblom, Annika, Hunter, David J., Joshi, Amit D., Schafmayer, Clemens, Scacheri, Peter C., Kundaje, Anshul, Schoen, Robert E., Hampe, Jochen, Stadler, Zsofia K., Vodicka, Pavel, Vodickova, Ludmila, Vymetalkova, Veronika, Edlund, Christopher K., Gauderman, W. James, Shibata, David, Toland, Amanda, Markowitz, Sanford, Kim, Andre, Chanock, Stephen J., van Duijnhoven, Franzel, Feskens, Edith J. M., Sakoda, Lori C., Gago-Dominguez, Manuela, Wolk, Alicja, Pardini, Barbara, FitzGerald, Liesel M., Lee, Soo Chin, Ogino, Shuji, Bien, Stephanie A., Kooperberg, Charles, Li, Christopher I., Lin, Yi, Prentice, Ross, Qu, Conghui, Bézieau, Stéphane, Yamaji, Taiki, Sawada, Norie, Iwasaki, Motoki, Le Marchand, Loic, Wu, Anna H., Qu, Chenxu, McNeil, Caroline E., Coetzee, Gerhard, Hayward, Caroline, Deary, Ian J., Harris, Sarah E., Theodoratou, Evropi, Reid, Stuart, Walker, Marion, Ooi, Li Yin, Lau, Ken S., Zhao, Hongyu, Hsu, Li, Cai, Qiuyin, Dunlop, Malcolm G., Gruber, Stephen B., Houlston, Richard S., Moreno, Victor, Casey, Graham, Peters, Ulrike, Tomlinson, Ian, and Zheng, Wei

Published
2024
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8. Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes

Author

Bradfield, Jonathan P., Kember, Rachel L., Ulrich, Anna, Balkhiyarova, Zhanna, Alyass, Akram, Aris, Izzuddin M., Bell, Joshua A., Broadaway, K. Alaine, Chen, Zhanghua, Chai, Jin-Fang, Davies, Neil M., Fernandez-Orth, Dietmar, Bustamante, Mariona, Fore, Ruby, Ganguli, Amitavo, Heiskala, Anni, Hottenga, Jouke-Jan, Íñiguez, Carmen, Kobes, Sayuko, Leinonen, Jaakko, Lowry, Estelle, Lyytikainen, Leo-Pekka, Mahajan, Anubha, Pitkänen, Niina, Schnurr, Theresia M., Have, Christian Theil, Strachan, David P., Thiering, Elisabeth, Vogelezang, Suzanne, Wade, Kaitlin H., Wang, Carol A., Wong, Andrew, Holm, Louise Aas, Chesi, Alessandra, Choong, Catherine, Cruz, Miguel, Elliott, Paul, Franks, Steve, Frithioff-Bøjsøe, Christine, Gauderman, W. James, Glessner, Joseph T., Gilsanz, Vicente, Griesman, Kendra, Hanson, Robert L., Kaakinen, Marika, Kalkwarf, Heidi, Kelly, Andrea, Kindler, Joseph, Kähönen, Mika, Lanca, Carla, Lappe, Joan, Lee, Nanette R., McCormack, Shana, Mentch, Frank D., Mitchell, Jonathan A., Mononen, Nina, Niinikoski, Harri, Oken, Emily, Pahkala, Katja, Sim, Xueling, Teo, Yik-Ying, Baier, Leslie J., van Beijsterveldt, Toos, Adair, Linda S., Boomsma, Dorret I., de Geus, Eco, Guxens, Mònica, Eriksson, Johan G., Felix, Janine F., Gilliland, Frank D., Biobank, Penn Medicine, Hansen, Torben, Hardy, Rebecca, Hivert, Marie-France, Holm, Jens-Christian, Jaddoe, Vincent W. V., Järvelin, Marjo-Riitta, Lehtimäki, Terho, Mackey, David A., Meyre, David, Mohlke, Karen L., Mykkänen, Juha, Oberfield, Sharon, Pennell, Craig E., Perry, John R. B., Raitakari, Olli, Rivadeneira, Fernando, Saw, Seang-Mei, Sebert, Sylvain, Shepherd, John A., Standl, Marie, Sørensen, Thorkild I. A., Timpson, Nicholas J., Torrent, Maties, Willemsen, Gonneke, Hypponen, Elina, Power, Chris, McCarthy, Mark I., Freathy, Rachel M., Widén, Elisabeth, Hakonarson, Hakon, Prokopenko, Inga, Voight, Benjamin F., Zemel, Babette S., Grant, Struan F. A., and Cousminer, Diana L.

Published
2024
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9. The genetic determinants of recurrent somatic mutations in 43,693 blood genomes

Author

Weinstock, Joshua S, Laurie, Cecelia A, Broome, Jai G, Taylor, Kent D, Guo, Xiuqing, Shuldiner, Alan R, O’Connell, Jeffrey R, Lewis, Joshua P, Boerwinkle, Eric, Barnes, Kathleen C, Chami, Nathalie, Kenny, Eimear E, Loos, Ruth JF, Fornage, Myriam, Redline, Susan, Cade, Brian E, Gilliland, Frank D, Chen, Zhanghua, Gauderman, W James, Kumar, Rajesh, Grammer, Leslie, Schleimer, Robert P, Psaty, Bruce M, Bis, Joshua C, Brody, Jennifer A, Silverman, Edwin K, Yun, Jeong H, Qiao, Dandi, Weiss, Scott T, Lasky-Su, Jessica, DeMeo, Dawn L, Palmer, Nicholette D, Freedman, Barry I, Bowden, Donald W, Cho, Michael H, Vasan, Ramachandran S, Johnson, Andrew D, Yanek, Lisa R, Becker, Lewis C, Kardia, Sharon, He, Jiang, Kaplan, Robert, Heckbert, Susan R, Smith, Nicholas L, Wiggins, Kerri L, Arnett, Donna K, Irvin, Marguerite R, Tiwari, Hemant, Correa, Adolfo, Raffield, Laura M, Gao, Yan, de Andrade, Mariza, Rotter, Jerome I, Rich, Stephen S, Manichaikul, Ani W, Konkle, Barbara A, Johnsen, Jill M, Wheeler, Marsha M, Custer, Brian S, Duggirala, Ravindranath, Curran, Joanne E, Blangero, John, Gui, Hongsheng, Xiao, Shujie, Williams, L Keoki, Meyers, Deborah A, Li, Xingnan, Ortega, Victor, McGarvey, Stephen, Gu, C Charles, Chen, Yii-Der Ida, Lee, Wen-Jane, Shoemaker, M Benjamin, Darbar, Dawood, Roden, Dan, Albert, Christine, Kooperberg, Charles, Desai, Pinkal, Blackwell, Thomas W, Abecasis, Goncalo R, Smith, Albert V, Kang, Hyun M, Mathias, Rasika, Natarajan, Pradeep, Jaiswal, Siddhartha, Reiner, Alexander P, Bick, Alexander G, and Consortium, NHLBI Trans-Omics for Precision Medicine

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Lung, Genetic Testing, Clinical Research, Biotechnology, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Humans, Middle Aged, Hematopoiesis, Mutation, Germ-Line Mutation, Mutation, Missense, Phenotype, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
Abstract

Nononcogenic somatic mutations are thought to be uncommon and inconsequential. To test this, we analyzed 43,693 National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine blood whole genomes from 37 cohorts and identified 7131 non-missense somatic mutations that are recurrently mutated in at least 50 individuals. These recurrent non-missense somatic mutations (RNMSMs) are not clearly explained by other clonal phenomena such as clonal hematopoiesis. RNMSM prevalence increased with age, with an average 50-year-old having 27 RNMSMs. Inherited germline variation associated with RNMSM acquisition. These variants were found in genes involved in adaptive immune function, proinflammatory cytokine production, and lymphoid lineage commitment. In addition, the presence of eight specific RNMSMs associated with blood cell traits at effect sizes comparable to Mendelian genetic mutations. Overall, we found that somatic mutations in blood are an unexpectedly common phenomenon with ancestry-specific determinants and human health consequences.

Published
2023

10. Genome-Wide Interaction Analysis of Genetic Variants With Menopausal Hormone Therapy for Colorectal Cancer Risk.

Author

Tian, Yu, Kim, Andre E, Bien, Stephanie A, Lin, Yi, Qu, Conghui, Harrison, Tabitha A, Carreras-Torres, Robert, Díez-Obrero, Virginia, Dimou, Niki, Drew, David A, Hidaka, Akihisa, Huyghe, Jeroen R, Jordahl, Kristina M, Morrison, John, Murphy, Neil, Obón-Santacana, Mireia, Ulrich, Cornelia M, Ose, Jennifer, Peoples, Anita R, Ruiz-Narvaez, Edward A, Shcherbina, Anna, Stern, Mariana C, Su, Yu-Ru, van Duijnhoven, Franzel JB, Arndt, Volker, Baurley, James W, Berndt, Sonja I, Bishop, D Timothy, Brenner, Hermann, Buchanan, Daniel D, Chan, Andrew T, Figueiredo, Jane C, Gallinger, Steven, Gruber, Stephen B, Harlid, Sophia, Hoffmeister, Michael, Jenkins, Mark A, Joshi, Amit D, Keku, Temitope O, Larsson, Susanna C, Le Marchand, Loic, Li, Li, Giles, Graham G, Milne, Roger L, Nan, Hongmei, Nassir, Rami, Ogino, Shuji, Budiarto, Arif, Platz, Elizabeth A, Potter, John D, Prentice, Ross L, Rennert, Gad, Sakoda, Lori C, Schoen, Robert E, Slattery, Martha L, Thibodeau, Stephen N, Van Guelpen, Bethany, Visvanathan, Kala, White, Emily, Wolk, Alicja, Woods, Michael O, Wu, Anna H, Campbell, Peter T, Casey, Graham, Conti, David V, Gunter, Marc J, Kundaje, Anshul, Lewinger, Juan Pablo, Moreno, Victor, Newcomb, Polly A, Pardamean, Bens, Thomas, Duncan C, Tsilidis, Konstantinos K, Peters, Ulrike, Gauderman, W James, Hsu, Li, and Chang-Claude, Jenny

Subjects
Humans, Colorectal Neoplasms, Estrogens, Progestins, Risk Factors, Case-Control Studies, Menopause, Polymorphism, Single Nucleotide, Female, Aging, Digestive Diseases, Estrogen, Colo-Rectal Cancer, Genetics, Prevention, Human Genome, Clinical Research, Cancer, 2.1 Biological and endogenous factors, Aetiology, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

BackgroundThe use of menopausal hormone therapy (MHT) may interact with genetic variants to influence colorectal cancer (CRC) risk.MethodsWe conducted a genome-wide, gene-environment interaction between single nucleotide polymorphisms and the use of any MHT, estrogen only, and combined estrogen-progestogen therapy with CRC risk, among 28 486 postmenopausal women (11 519 CRC patients and 16 967 participants without CRC) from 38 studies, using logistic regression, 2-step method, and 2- or 3-degree-of-freedom joint test. A set-based score test was applied for rare genetic variants.ResultsThe use of any MHT, estrogen only and estrogen-progestogen were associated with a reduced CRC risk (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.64 to 0.78; OR = 0.65, 95% CI = 0.53 to 0.79; and OR = 0.73, 95% CI = 0.59 to 0.90, respectively). The 2-step method identified a statistically significant interaction between a GRIN2B variant rs117868593 and MHT use, whereby MHT-associated CRC risk was statistically significantly reduced in women with the GG genotype (OR = 0.68, 95% CI = 0.64 to 0.72) but not within strata of GC or CC genotypes. A statistically significant interaction between a DCBLD1 intronic variant at 6q22.1 (rs10782186) and MHT use was identified by the 2-degree-of-freedom joint test. The MHT-associated CRC risk was reduced with increasing number of rs10782186-C alleles, showing odds ratios of 0.78 (95% CI = 0.70 to 0.87) for TT, 0.68 (95% CI = 0.63 to 0.73) for TC, and 0.66 (95% CI = 0.60 to 0.74) for CC genotypes. In addition, 5 genes in rare variant analysis showed suggestive interactions with MHT (2-sided P

Published
2022

11. Probing the diabetes and colorectal cancer relationship using gene – environment interaction analyses

Author

Dimou, Niki, Kim, Andre E., Flanagan, Orlagh, Murphy, Neil, Diez-Obrero, Virginia, Shcherbina, Anna, Aglago, Elom K., Bouras, Emmanouil, Campbell, Peter T., Casey, Graham, Gallinger, Steven, Gruber, Stephen B., Jenkins, Mark A., Lin, Yi, Moreno, Victor, Ruiz-Narvaez, Edward, Stern, Mariana C., Tian, Yu, Tsilidis, Kostas K., Arndt, Volker, Barry, Elizabeth L., Baurley, James W., Berndt, Sonja I., Bézieau, Stéphane, Bien, Stephanie A., Bishop, D. Timothy, Brenner, Hermann, Budiarto, Arif, Carreras-Torres, Robert, Cenggoro, Tjeng Wawan, Chan, Andrew T., Chang-Claude, Jenny, Chanock, Stephen J., Chen, Xuechen, Conti, David V., Dampier, Christopher H., Devall, Matthew, Drew, David A., Figueiredo, Jane C., Giles, Graham G., Gsur, Andrea, Harrison, Tabitha A., Hidaka, Akihisa, Hoffmeister, Michael, Huyghe, Jeroen R., Jordahl, Kristina, Kawaguchi, Eric, Keku, Temitope O., Larsson, Susanna C., Le Marchand, Loic, Lewinger, Juan Pablo, Li, Li, Mahesworo, Bharuno, Morrison, John, Newcomb, Polly A., Newton, Christina C., Obon-Santacana, Mireia, Ose, Jennifer, Pai, Rish K., Palmer, Julie R., Papadimitriou, Nikos, Pardamean, Bens, Peoples, Anita R., Pharoah, Paul D. P., Platz, Elizabeth A., Potter, John D., Rennert, Gad, Scacheri, Peter C., Schoen, Robert E., Su, Yu-Ru, Tangen, Catherine M., Thibodeau, Stephen N., Thomas, Duncan C., Ulrich, Cornelia M., Um, Caroline Y., van Duijnhoven, Franzel J. B., Visvanathan, Kala, Vodicka, Pavel, Vodickova, Ludmila, White, Emily, Wolk, Alicja, Woods, Michael O., Qu, Conghui, Kundaje, Anshul, Hsu, Li, Gauderman, W. James, Gunter, Marc J., and Peters, Ulrike

Published
2023
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12. Genome-wide interaction study of dietary intake of fibre, fruits, and vegetables with risk of colorectal cancer

Author

Papadimitriou, Nikos, Kim, Andre, Kawaguchi, Eric S., Morrison, John, Diez-Obrero, Virginia, Albanes, Demetrius, Berndt, Sonja I., Bézieau, Stéphane, Bien, Stephanie A., Bishop, D Timothy, Bouras, Emmanouil, Brenner, Hermann, Buchanan, Daniel D., Campbell, Peter T., Carreras-Torres, Robert, Chan, Andrew T., Chang-Claude, Jenny, Conti, David V., Devall, Matthew A., Dimou, Niki, Drew, David A., Gruber, Stephen B., Harrison, Tabitha A., Hoffmeister, Michael, Huyghe, Jeroen R., Joshi, Amit D., Keku, Temitope O., Kundaje, Anshul, Küry, Sébastien, Le Marchand, Loic, Lewinger, Juan Pablo, Li, Li, Lynch, Brigid M., Moreno, Victor, Newton, Christina C., Obón-Santacana, Mireia, Ose, Jennifer, Pellatt, Andrew J., Peoples, Anita R., Platz, Elizabeth A., Qu, Conghui, Rennert, Gad, Ruiz-Narvaez, Edward, Shcherbina, Anna, Stern, Mariana C., Su, Yu-Ru, Thomas, Duncan C., Thomas, Claire E., Tian, Yu, Tsilidis, Konstantinos K., Ulrich, Cornelia M., Um, Caroline Y., Visvanathan, Kala, Wang, Jun, White, Emily, Woods, Michael O., Schmit, Stephanie L., Macrae, Finlay, Potter, John D., Hopper, John L., Peters, Ulrike, Murphy, Neil, Hsu, Li, Gunter, Marc J., and Gauderman, W. James

Published
2024
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14. A scalable hierarchical lasso for gene-environment interactions

Author

Zemlianskaia, Natalia, Gauderman, W. James, and Lewinger, Juan Pablo

Subjects
Statistics - Methodology, Quantitative Biology - Quantitative Methods
Abstract

We describe a regularized regression model for the selection of gene-environment (GxE) interactions. The model focuses on a single environmental exposure and induces a main-effect-before-interaction hierarchical structure. We propose an efficient fitting algorithm and screening rules that can discard large numbers of irrelevant predictors with high accuracy. We present simulation results showing that the model outperforms existing joint selection methods for (GxE) interactions in terms of selection performance, scalability and speed, and provide a real data application. Our implementation is available in the gesso R package.

Published
2021
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16. Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk

Author

Shrine, Nick, Izquierdo, Abril G., Chen, Jing, Packer, Richard, Hall, Robert J., Guyatt, Anna L., Batini, Chiara, Thompson, Rebecca J., Pavuluri, Chandan, Malik, Vidhi, Hobbs, Brian D., Moll, Matthew, Kim, Wonji, Tal-Singer, Ruth, Bakke, Per, Fawcett, Katherine A., John, Catherine, Coley, Kayesha, Piga, Noemi Nicole, Pozarickij, Alfred, Lin, Kuang, Millwood, Iona Y., Chen, Zhengming, Li, Liming, Wijnant, Sara R. A., Lahousse, Lies, Brusselle, Guy, Uitterlinden, Andre G., Manichaikul, Ani, Oelsner, Elizabeth C., Rich, Stephen S., Barr, R. Graham, Kerr, Shona M., Vitart, Veronique, Brown, Michael R., Wielscher, Matthias, Imboden, Medea, Jeong, Ayoung, Bartz, Traci M., Gharib, Sina A., Flexeder, Claudia, Karrasch, Stefan, Gieger, Christian, Peters, Annette, Stubbe, Beate, Hu, Xiaowei, Ortega, Victor E., Meyers, Deborah A., Bleecker, Eugene R., Gabriel, Stacey B., Gupta, Namrata, Smith, Albert Vernon, Luan, Jian’an, Zhao, Jing-Hua, Hansen, Ailin F., Langhammer, Arnulf, Willer, Cristen, Bhatta, Laxmi, Porteous, David, Smith, Blair H., Campbell, Archie, Sofer, Tamar, Lee, Jiwon, Daviglus, Martha L., Yu, Bing, Lim, Elise, Xu, Hanfei, O’Connor, George T., Thareja, Gaurav, Albagha, Omar M. E., Suhre, Karsten, Granell, Raquel, Faquih, Tariq O., Hiemstra, Pieter S., Slats, Annelies M., Mullin, Benjamin H., Hui, Jennie, James, Alan, Beilby, John, Patasova, Karina, Hysi, Pirro, Koskela, Jukka T., Wyss, Annah B., Jin, Jianping, Sikdar, Sinjini, Lee, Mikyeong, May-Wilson, Sebastian, Pirastu, Nicola, Kentistou, Katherine A., Joshi, Peter K., Timmers, Paul R. H. J., Williams, Alexander T., Free, Robert C., Wang, Xueyang, Morrison, John L., Gilliland, Frank D., Chen, Zhanghua, Wang, Carol A., Foong, Rachel E., Harris, Sarah E., Taylor, Adele, Redmond, Paul, Cook, James P., Mahajan, Anubha, Lind, Lars, Palviainen, Teemu, Lehtimäki, Terho, Raitakari, Olli T., Kaprio, Jaakko, Rantanen, Taina, Pietiläinen, Kirsi H., Cox, Simon R., Pennell, Craig E., Hall, Graham L., Gauderman, W. James, Brightling, Chris, Wilson, James F., Vasankari, Tuula, Laitinen, Tarja, Salomaa, Veikko, Mook-Kanamori, Dennis O., Timpson, Nicholas J., Zeggini, Eleftheria, Dupuis, Josée, Hayward, Caroline, Brumpton, Ben, Langenberg, Claudia, Weiss, Stefan, Homuth, Georg, Schmidt, Carsten Oliver, Probst-Hensch, Nicole, Jarvelin, Marjo-Riitta, Morrison, Alanna C., Polasek, Ozren, Rudan, Igor, Lee, Joo-Hyeon, Sayers, Ian, Rawlins, Emma L., Dudbridge, Frank, Silverman, Edwin K., Strachan, David P., Walters, Robin G., Morris, Andrew P., London, Stephanie J., Cho, Michael H., Wain, Louise V., Hall, Ian P., and Tobin, Martin D.

Published
2023
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17. Increased burden of familial-associated early-onset cancer risk among minority Americans compared to non-Latino Whites.

Author

Feng, Qianxi, Nickels, Eric, Muskens, Ivo S, de Smith, Adam J, Gauderman, W James, Yee, Amy C, Ricker, Charite, Mack, Thomas, Leavitt, Andrew D, Godley, Lucy A, and Wiemels, Joseph L

Subjects
early-onset cancer, epidemiology, familial risk, global health, hispanic paradox, human, latino americans, linked cancer registry, race/ethnicity, Biochemistry and Cell Biology
Abstract

BackgroundThe role of race/ethnicity in genetic predisposition of early-onset cancers can be estimated by comparing family-based cancer concordance rates among ethnic groups.MethodsWe used linked California health registries to evaluate the relative cancer risks for first-degree relatives of patients diagnosed between ages 0 and 26, and the relative risks of developing distinct second primary malignancies (SPMs). From 1989 to 2015, we identified 29,631 cancer patients and 62,863 healthy family members. We calculated the standardized incident ratios (SIRs) of early-onset primary cancers diagnosed in proband siblings and mothers, as well as SPMs detected among early-onset patients. Analyses were stratified by self-identified race/ethnicity.ResultsGiven probands with cancer, there were increased relative risks of any cancer for siblings and mothers (SIR = 3.32; 95% confidence interval [CI]: 2.85-3.85) and of SPMs (SIR = 7.27; 95% CI: 6.56-8.03). Given a proband with solid cancer, both Latinos (SIR = 4.98; 95% CI: 3.82-6.39) and non-Latino Blacks (SIR = 7.35; 95% CI: 3.36-13.95) exhibited significantly higher relative risk of any cancer in siblings and mothers when compared to non-Latino White subjects (SIR = 3.02; 95% CI: 2.12-4.16). For hematologic cancers, higher familial risk was evident for Asian/Pacific Islanders (SIR = 7.56; 95% CI: 3.26-14.90) compared to non-Latino whites (SIR = 2.69; 95% CI: 1.62-4.20).ConclusionsThe data support a need for increased attention to the genetics of early-onset cancer predisposition and environmental factors in race/ethnic minority families in the United States.FundingThis work was supported by the V Foundation for funding this work (Grant FP067172).

Published
2021

18. Genome-wide interaction analysis of folate for colorectal cancer risk

Author

Bouras, Emmanouil, Kim, Andre E., Lin, Yi, Morrison, John, Du, Mengmeng, Albanes, Demetrius, Barry, Elizabeth L., Baurley, James W., Berndt, Sonja I., Bien, Stephanie A., Bishop, Timothy D., Brenner, Hermann, Budiarto, Arif, Burnett-Hartman, Andrea, Campbell, Peter T., Carreras-Torres, Robert, Casey, Graham, Cenggoro, Tjeng Wawan, Chan, Andrew T., Chang-Claude, Jenny, Conti, David V., Cotterchio, Michelle, Devall, Matthew, Diez-Obrero, Virginia, Dimou, Niki, Drew, David A., Figueiredo, Jane C., Giles, Graham G., Gruber, Stephen B., Gunter, Marc J., Harrison, Tabitha A., Hidaka, Akihisa, Hoffmeister, Michael, Huyghe, Jeroen R., Joshi, Amit D., Kawaguchi, Eric S., Keku, Temitope O., Kundaje, Anshul, Le Marchand, Loic, Lewinger, Juan Pablo, Li, Li, Lynch, Brigid M., Mahesworo, Bharuno, Männistö, Satu, Moreno, Victor, Murphy, Neil, Newcomb, Polly A., Obón-Santacana, Mireia, Ose, Jennifer, Palmer, Julie R., Papadimitriou, Nikos, Pardamean, Bens, Pellatt, Andrew J., Peoples, Anita R., Platz, Elizabeth A., Potter, John D., Qi, Lihong, Qu, Conghui, Rennert, Gad, Ruiz-Narvaez, Edward, Sakoda, Lori C., Schmit, Stephanie L., Shcherbina, Anna, Stern, Mariana C., Su, Yu-Ru, Tangen, Catherine M., Thomas, Duncan C., Tian, Yu, Um, Caroline Y., van Duijnhoven, Franzel JB., Van Guelpen, Bethany, Visvanathan, Kala, Wang, Jun, White, Emily, Wolk, Alicja, Woods, Michael O., Ulrich, Cornelia M., Hsu, Li, Gauderman, W James, Peters, Ulrike, and Tsilidis, Konstantinos K.

Published
2023
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19. Mapping the 17q12-21.1 Locus for Variants Associated with Early-Onset Asthma in African Americans.

Author

Gui, Hongsheng, Levin, Albert M, Hu, Donglei, Sleiman, Patrick, Xiao, Shujie, Mak, Angel CY, Yang, Mao, Barczak, Andrea J, Huntsman, Scott, Eng, Celeste, Hochstadt, Samantha, Zhang, Ellen, Whitehouse, Kyle, Simons, Samantha, Cabral, Whitney, Takriti, Sami, Abecasis, Gonçalo, Blackwell, Thomas W, Kang, Hyun Min, Nickerson, Deborah A, Germer, Soren, Lanfear, David E, Gilliland, Frank, Gauderman, W James, Kumar, Rajesh, Erle, David J, Martinez, Fernando D, Hakonarson, Hakon, Burchard, Esteban G, and Williams, L Keoki

Subjects
Lung, Asthma, Genetics, Aetiology, 2.1 Biological and endogenous factors, Respiratory, Adolescent, Adult, Black or African American, Age of Onset, Child, Child, Preschool, Chromosome Mapping, Chromosomes, Human, Pair 17, Female, Genetic Association Studies, Genetic Predisposition to Disease, Genetic Variation, Humans, Infant, Infant, Newborn, Linkage Disequilibrium, Male, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait Loci, United States, White People, Young Adult, asthma, African Americans, chromosome 17, GSDMB, ORMDL3, Medical and Health Sciences, Respiratory System
Abstract

Rationale: The 17q12-21.1 locus is one of the most highly replicated genetic associations with asthma. Individuals of African descent have lower linkage disequilibrium in this region, which could facilitate identifying causal variants.Objectives: To identify functional variants at 17q12-21.1 associated with early-onset asthma among African American individuals.Methods: We evaluated African American participants from SAPPHIRE (Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity) (n = 1,940), SAGE II (Study of African Americans, Asthma, Genes and Environment) (n = 885), and GCPD-A (Study of the Genetic Causes of Complex Pediatric Disorders-Asthma) (n = 2,805). Associations with asthma onset at ages under 5 years were meta-analyzed across cohorts. The lead signal was reevaluated considering haplotypes informed by genetic ancestry (i.e., African vs. European). Both an expression-quantitative trait locus analysis and a phenome-wide association study were performed on the lead variant.Measurements and Main Results: The meta-analyzed results from SAPPHIRE, SAGE II, and the GCPD-A identified rs11078928 as the top association for early-onset asthma. A haplotype analysis suggested that the asthma association partitioned most closely with the rs11078928 genotype. Genetic ancestry did not appear to influence the effect of this variant. In the expression-quantitative trait locus analysis, rs11078928 was related to alternative splicing of GSDMB (gasdermin-B) transcripts. The phenome-wide association study of rs11078928 suggested that this variant was predominantly associated with asthma and asthma-associated symptoms.Conclusions: A splice-acceptor polymorphism appears to be a causal variant for asthma at the 17q12-21.1 locus. This variant appears to have the same magnitude of effect in individuals of African and European descent.

Published
2021

20. Author Correction: Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk

Author

Shrine, Nick, Izquierdo, Abril G., Chen, Jing, Packer, Richard, Hall, Robert J., Guyatt, Anna L., Batini, Chiara, Thompson, Rebecca J., Pavuluri, Chandan, Malik, Vidhi, Hobbs, Brian D., Moll, Matthew, Kim, Wonji, Tal-Singer, Ruth, Bakke, Per, Fawcett, Katherine A., John, Catherine, Coley, Kayesha, Piga, Noemi Nicole, Pozarickij, Alfred, Lin, Kuang, Millwood, Iona Y., Chen, Zhengming, Li, Liming, Wijnant, Sara R. A., Lahousse, Lies, Brusselle, Guy, Uitterlinden, Andre G., Manichaikul, Ani, Oelsner, Elizabeth C., Rich, Stephen S., Barr, R. Graham, Kerr, Shona M., Vitart, Veronique, Brown, Michael R., Wielscher, Matthias, Imboden, Medea, Jeong, Ayoung, Bartz, Traci M., Gharib, Sina A., Flexeder, Claudia, Karrasch, Stefan, Gieger, Christian, Peters, Annette, Stubbe, Beate, Hu, Xiaowei, Ortega, Victor E., Meyers, Deborah A., Bleecker, Eugene R., Gabriel, Stacey B., Gupta, Namrata, Smith, Albert Vernon, Luan, Jian’an, Zhao, Jing-Hua, Hansen, Ailin F., Langhammer, Arnulf, Willer, Cristen, Bhatta, Laxmi, Porteous, David, Smith, Blair H., Campbell, Archie, Sofer, Tamar, Lee, Jiwon, Daviglus, Martha L., Yu, Bing, Lim, Elise, Xu, Hanfei, O’Connor, George T., Thareja, Gaurav, Albagha, Omar M. E., Suhre, Karsten, Granell, Raquel, Faquih, Tariq O., Hiemstra, Pieter S., Slats, Annelies M., Mullin, Benjamin H., Hui, Jennie, James, Alan, Beilby, John, Patasova, Karina, Hysi, Pirro, Koskela, Jukka T., Wyss, Annah B., Jin, Jianping, Sikdar, Sinjini, Lee, Mikyeong, May-Wilson, Sebastian, Pirastu, Nicola, Kentistou, Katherine A., Joshi, Peter K., Timmers, Paul R. H. J., Williams, Alexander T., Free, Robert C., Wang, Xueyang, Morrison, John L., Gilliland, Frank D., Chen, Zhanghua, Wang, Carol A., Foong, Rachel E., Harris, Sarah E., Taylor, Adele, Redmond, Paul, Cook, James P., Mahajan, Anubha, Lind, Lars, Palviainen, Teemu, Lehtimäki, Terho, Raitakari, Olli T., Kaprio, Jaakko, Rantanen, Taina, Pietiläinen, Kirsi H., Cox, Simon R., Pennell, Craig E., Hall, Graham L., Gauderman, W. James, Brightling, Chris, Wilson, James F., Vasankari, Tuula, Laitinen, Tarja, Salomaa, Veikko, Mook-Kanamori, Dennis O., Timpson, Nicholas J., Zeggini, Eleftheria, Dupuis, Josée, Hayward, Caroline, Brumpton, Ben, Langenberg, Claudia, Weiss, Stefan, Homuth, Georg, Schmidt, Carsten Oliver, Probst-Hensch, Nicole, Jarvelin, Marjo-Riitta, Morrison, Alanna C., Polasek, Ozren, Rudan, Igor, Lee, Joo-Hyeon, Sayers, Ian, Rawlins, Emma L., Dudbridge, Frank, Silverman, Edwin K., Strachan, David P., Walters, Robin G., Morris, Andrew P., London, Stephanie J., Cho, Michael H., Wain, Louise V., Hall, Ian P., and Tobin, Martin D.

Published
2023
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22. Functional informed genome‐wide interaction analysis of body mass index, diabetes and colorectal cancer risk

Author

Xia, Zhiyu, Su, Yu‐Ru, Petersen, Paneen, Qi, Lihong, Kim, Andre E, Figueiredo, Jane C, Lin, Yi, Nan, Hongmei, Sakoda, Lori C, Albanes, Demetrius, Berndt, Sonja I, Bézieau, Stéphane, Bien, Stephanie, Buchanan, Daniel D, Casey, Graham, Chan, Andrew T, Conti, David V, Drew, David A, Gallinger, Steven J, Gauderman, W James, Giles, Graham G, Gruber, Stephen B, Gunter, Marc J, Hoffmeister, Michael, Jenkins, Mark A, Joshi, Amit D, Le Marchand, Loic, Lewinger, Juan P, Li, Li, Lindor, Noralane M, Moreno, Victor, Murphy, Neil, Nassir, Rami, Newcomb, Polly A, Ogino, Shuji, Rennert, Gad, Song, Mingyang, Wang, Xiaoliang, Wolk, Alicja, Woods, Michael O, Brenner, Hermann, White, Emily, Slattery, Martha L, Giovannucci, Edward L, Chang‐Claude, Jenny, Pharoah, Paul DP, Hsu, Li, Campbell, Peter T, and Peters, Ulrike

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Digestive Diseases, Human Genome, Genetics, Cancer, Diabetes, Prevention, Nutrition, Colo-Rectal Cancer, Metabolic and endocrine, ATPases Associated with Diverse Cellular Activities, Aged, Body Mass Index, Colorectal Neoplasms, Databases, Genetic, Diabetes Mellitus, Type 2, Female, Gene Expression, Genotype, Hepatocyte Nuclear Factor 3-alpha, Humans, Male, Microtubule-Associated Proteins, Middle Aged, Obesity, Phenotype, Proteasome Endopeptidase Complex, Protein Tyrosine Phosphatase, Non-Receptor Type 2, Sex Factors, Sialic Acid Binding Ig-like Lectin 3, Voltage-Gated Sodium Channel beta-1 Subunit, BMI, colorectal cancer, diabetes, gene expression, gene-environmental interaction, Biochemistry and Cell Biology, Oncology and carcinogenesis
Abstract

BackgroundBody mass index (BMI) and diabetes are established risk factors for colorectal cancer (CRC), likely through perturbations in metabolic traits (e.g. insulin resistance and glucose homeostasis). Identification of interactions between variation in genes and these metabolic risk factors may identify novel biologic insights into CRC etiology.MethodsTo improve statistical power and interpretation for gene-environment interaction (G × E) testing, we tested genetic variants that regulate expression of a gene together for interaction with BMI (kg/m2 ) and diabetes on CRC risk among 26 017 cases and 20 692 controls. Each variant was weighted based on PrediXcan analysis of gene expression data from colon tissue generated in the Genotype-Tissue Expression Project for all genes with heritability ≥1%. We used a mixed-effects model to jointly measure the G × E interaction in a gene by partitioning the interactions into the predicted gene expression levels (fixed effects), and residual G × E effects (random effects). G × BMI analyses were stratified by sex as BMI-CRC associations differ by sex. We used false discovery rates to account for multiple comparisons and reported all results with FDR

Published
2020

23. A genome-wide association study on medulloblastoma

Author

Dahlin, Anna M, Wibom, Carl, Andersson, Ulrika, Bybjerg-Grauholm, Jonas, Deltour, Isabelle, Hougaard, David M, Scheurer, Michael E, Lau, Ching C, McKean-Cowdin, Roberta, Kennedy, Rebekah J, Hung, Long T, Yee, Janis, Margol, Ashley S, Barrington-Trimis, Jessica, Gauderman, W James, Feychting, Maria, Schüz, Joachim, Röösli, Martin, Kjaerheim, Kristina, Januszkiewicz-Lewandowska, Danuta, Fichna, Marta, Nowak, Jerzy, Searles Nielsen, Susan, Asgharzadeh, Shahab, Mirabello, Lisa, Hjalmars, Ulf, and Melin, Beatrice

Subjects
Brain Cancer, Cancer, Prevention, Rare Diseases, Pediatric, Human Genome, Brain Disorders, Genetics, Aetiology, 2.1 Biological and endogenous factors, Biomarkers, Tumor, Case-Control Studies, Cerebellar Neoplasms, Cohort Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Medulloblastoma, Polymorphism, Single Nucleotide, Prognosis, Cefalo Study Group, Adolescents and young adults, CNS cancers, Epidemiology, Genetics of risk, outcome, and prevention, Pediatric cancers, Neurosciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

IntroductionMedulloblastoma is a malignant embryonal tumor of the cerebellum that occurs predominantly in children. To find germline genetic variants associated with medulloblastoma risk, we conducted a genome-wide association study (GWAS) including 244 medulloblastoma cases and 247 control subjects from Sweden and Denmark.MethodsGenotyping was performed using Illumina BeadChips, and untyped variants were imputed using IMPUTE2.ResultsFifty-nine variants in 11 loci were associated with increased medulloblastoma risk (p

Published
2020

24. Asthma and its relationship to mitochondrial copy number: Results from the Asthma Translational Genomics Collaborative (ATGC) of the Trans-Omics for Precision Medicine (TOPMed) program.

Author

Cocco, Maxwell P, White, Evan, Xiao, Shujie, Hu, Donglei, Mak, Angel, Sleiman, Patrick, Yang, Mao, Bobbitt, Kevin R, Gui, Hongsheng, Levin, Albert M, Hochstadt, Samantha, Whitehouse, Kyle, Rynkowski, Dean, Barczak, Andrea J, Abecasis, Gonçalo, Blackwell, Thomas W, Kang, Hyun Min, Nickerson, Deborah A, Germer, Soren, Ding, Jun, Lanfear, David E, Gilliland, Frank, Gauderman, W James, Kumar, Rajesh, Erle, David J, Martinez, Fernando, Hakonarson, Hakon, Burchard, Esteban G, and Williams, L Keoki

Subjects
Leukocytes, Humans, Asthma, Electron Transport Chain Complex Proteins, DNA, Mitochondrial, RNA, Flow Cytometry, Logistic Models, Proportional Hazards Models, Sensitivity and Specificity, Cohort Studies, Base Sequence, Adult, Middle Aged, African Americans, Female, Male, Young Adult, DNA Copy Number Variations, Translational Medical Research, Whole Genome Sequencing, Human Genome, Biotechnology, Lung, Clinical Research, Genetics, Respiratory, General Science & Technology
Abstract

BackgroundMitochondria support critical cellular functions, such as energy production through oxidative phosphorylation, regulation of reactive oxygen species, apoptosis, and calcium homeostasis.ObjectiveGiven the heightened level of cellular activity in patients with asthma, we sought to determine whether mitochondrial DNA (mtDNA) copy number measured in peripheral blood differed between individuals with and without asthma.MethodsWhole genome sequence data was generated as part of the Trans-Omics for Precision Medicine (TOPMed) Program on participants from the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE) and the Study of African Americans, Asthma, Genes, & Environment II (SAGE II). We restricted our analysis to individuals who self-identified as African American (3,651 asthma cases and 1,344 controls). Mitochondrial copy number was estimated using the sequencing read depth ratio for the mitochondrial and nuclear genomes. Respiratory complex expression was assessed using RNA-sequencing.ResultsAverage mitochondrial copy number was significantly higher among individuals with asthma when compared with controls (SAPPHIRE: 218.60 vs. 200.47, P

Published
2020

26. Two genome-wide interaction loci modify the association of nonsteroidal anti-inflammatory drugs with colorectal cancer

Author

Drew, David A., primary, Kim, Andre E., additional, Lin, Yi, additional, Qu, Conghui, additional, Morrison, John, additional, Lewinger, Juan Pablo, additional, Kawaguchi, Eric, additional, Wang, Jun, additional, Fu, Yubo, additional, Zemlianskaia, Natalia, additional, Díez-Obrero, Virginia, additional, Bien, Stephanie A., additional, Dimou, Niki, additional, Albanes, Demetrius, additional, Baurley, James W., additional, Wu, Anna H., additional, Buchanan, Daniel D., additional, Potter, John D., additional, Prentice, Ross L., additional, Harlid, Sophia, additional, Arndt, Volker, additional, Barry, Elizabeth L., additional, Berndt, Sonja I., additional, Bouras, Emmanouil, additional, Brenner, Hermann, additional, Budiarto, Arif, additional, Burnett-Hartman, Andrea, additional, Campbell, Peter T., additional, Carreras-Torres, Robert, additional, Casey, Graham, additional, Chang-Claude, Jenny, additional, Conti, David V., additional, Devall, Matthew A.M., additional, Figueiredo, Jane C., additional, Gruber, Stephen B., additional, Gsur, Andrea, additional, Gunter, Marc J., additional, Harrison, Tabitha A., additional, Hidaka, Akihisa, additional, Hoffmeister, Michael, additional, Huyghe, Jeroen R., additional, Jenkins, Mark A., additional, Jordahl, Kristina M., additional, Kundaje, Anshul, additional, Le Marchand, Loic, additional, Li, Li, additional, Lynch, Brigid M., additional, Murphy, Neil, additional, Nassir, Rami, additional, Newcomb, Polly A., additional, Newton, Christina C., additional, Obón-Santacana, Mireia, additional, Ogino, Shuji, additional, Ose, Jennifer, additional, Pai, Rish K., additional, Palmer, Julie R., additional, Papadimitriou, Nikos, additional, Pardamean, Bens, additional, Pellatt, Andrew J., additional, Peoples, Anita R., additional, Platz, Elizabeth A., additional, Rennert, Gad, additional, Ruiz-Narvaez, Edward, additional, Sakoda, Lori C., additional, Scacheri, Peter C., additional, Schmit, Stephanie L., additional, Schoen, Robert E., additional, Stern, Mariana C., additional, Su, Yu-Ru, additional, Thomas, Duncan C., additional, Tian, Yu, additional, Tsilidis, Konstantinos K., additional, Ulrich, Cornelia M., additional, Um, Caroline Y., additional, van Duijnhoven, Fränzel J.B., additional, Van Guelpen, Bethany, additional, White, Emily, additional, Hsu, Li, additional, Moreno, Victor, additional, Peters, Ulrike, additional, Chan, Andrew T., additional, and Gauderman, W. James, additional

Published
2024
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27. Does socioeconomic and environmental burden affect vulnerability to extreme air pollution and heat? A case-crossover study of mortality in California

Author

Azzouz, Mehjar, primary, Hasan, Zainab, additional, Rahman, Md Mostafijur, additional, Gauderman, W. James, additional, Lorenzo, Melissa, additional, Lurmann, Frederick W., additional, Eckel, Sandrah P., additional, Palinkas, Lawrence, additional, Johnston, Jill, additional, Hurlburt, Michael, additional, Silva, Sam J., additional, Schlaerth, Hannah, additional, Ko, Joseph, additional, Ban-Weiss, George, additional, McConnell, Rob, additional, Stockfelt, Leo, additional, and Garcia, Erika, additional

Published
2024
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29. Gene-lifestyle interactions in the genomics of human complex traits

Author

Laville, Vincent, Majarian, Timothy, Sung, Yun J., Schwander, Karen, Feitosa, Mary F., Chasman, Daniel I., Bentley, Amy R., Rotimi, Charles N., Cupples, L. Adrienne, de Vries, Paul S., Brown, Michael R., Morrison, Alanna C., Kraja, Aldi T., Province, Mike, Gu, C. Charles, Gauderman, W. James, Rao, D. C., Manning, Alisa K., and Aschard, Hugues

Published
2022
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30. Immune factors preceding diagnosis of glioma: a Prostate Lung Colorectal Ovarian Cancer Screening Trial nested case–control study

Author

Muskens, Ivo S, Zhou, Mi, Mccoy, Lucie, Bracci, Paige M, Hansen, Helen M, Gauderman, W James, Wiencke, John K, Wrensch, Margaret R, and Wiemels, Joseph L

Subjects
Biomedical and Clinical Sciences, Health Sciences, Oncology and Carcinogenesis, Prevention, Brain Cancer, Lung, Brain Disorders, Cancer, Ovarian Cancer, Urologic Diseases, Clinical Research, Genetics, Aging, Rare Diseases, allergy, glioma, PLCO, TGF-beta 1, TGF-β1
Abstract

BackgroundEpidemiological studies of adult glioma have identified genetic and environmental risk factors, but much remains unclear. The aim of the current study was to evaluate anthropometric, disease-related, and prediagnostic immune-related factors for relationship with glioma risk.MethodsWe conducted a nested case-control study among the intervention arm of the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial. One hundred and twenty-four glioma cases were identified and each matched to four controls. Baseline characteristics were collected at enrollment and were evaluated for association with glioma status. Serum specimens were collected at yearly intervals and were analyzed for immune-related factors including TGF-β1, TNF-α, total IgE, and allergen-specific IgE. Immune factors were evaluated at baseline in a multivariate conditional logistic regression model, along with one additional model that incorporated the latest available measurement.ResultsA family history of glioma among first-degree relatives was associated with increased glioma risk (OR = 4.41, P = .002). In multivariate modeling of immune factors at baseline, increased respiratory allergen-specific IgE was inversely associated with glioma risk (OR for allergen-specific IgE > 0.35 PAU/L: 0.59, P = .03). A logistic regression model that incorporated the latest available measurements found a similar association for allergen-specific IgE (P = .005) and showed that elevated TGF-β1 was associated with increased glioma risk (P-value for trend

Published
2019

31. An admixture mapping meta-analysis implicates genetic variation at 18q21 with asthma susceptibility in Latinos

Author

Gignoux, Christopher R, Torgerson, Dara G, Pino-Yanes, Maria, Uricchio, Lawrence H, Galanter, Joshua, Roth, Lindsey A, Eng, Celeste, Hu, Donglei, Nguyen, Elizabeth A, Huntsman, Scott, Mathias, Rasika A, Kumar, Rajesh, Rodriguez-Santana, Jose, Thakur, Neeta, Oh, Sam S, McGarry, Meghan, Moreno-Estrada, Andres, Sandoval, Karla, Winkler, Cheryl A, Seibold, Max A, Padhukasahasram, Badri, Conti, David V, Farber, Harold J, Avila, Pedro, Brigino-Buenaventura, Emerita, Lenoir, Michael, Meade, Kelley, Serebrisky, Denise, Borrell, Luisa N, Rodriguez-Cintron, William, Thyne, Shannon, Joubert, Bonnie R, Romieu, Isabelle, Levin, Albert M, Sienra-Monge, Juan-Jose, Del Rio-Navarro, Blanca Estela, Gan, Weiniu, Raby, Benjamin A, Weiss, Scott T, Bleecker, Eugene, Meyers, Deborah A, Martinez, Fernando J, Gauderman, W James, Gilliland, Frank, London, Stephanie J, Bustamante, Carlos D, Nicolae, Dan L, Ober, Carole, Sen, Saunak, Barnes, Kathleen, Williams, L Keoki, Hernandez, Ryan D, and Burchard, Esteban G

Subjects
Biomedical and Clinical Sciences, Immunology, Human Genome, Clinical Research, Lung, Asthma, Genetics, Aetiology, 2.1 Biological and endogenous factors, Respiratory, Chromosome Mapping, Chromosomes, Human, Pair 18, Genetic Predisposition to Disease, Hispanic or Latino, Humans, Polymorphism, Single Nucleotide, Smad2 Protein, asthma exacerbations, admixture mapping, meta-analysis, Latinos, SMAD2, gene expression, targeted sequencing, rare variation, Allergy
Abstract

BackgroundAsthma is a common but complex disease with racial/ethnic differences in prevalence, morbidity, and response to therapies.ObjectiveWe sought to perform an analysis of genetic ancestry to identify new loci that contribute to asthma susceptibility.MethodsWe leveraged the mixed ancestry of 3902 Latinos and performed an admixture mapping meta-analysis for asthma susceptibility. We replicated associations in an independent study of 3774 Latinos, performed targeted sequencing for fine mapping, and tested for disease correlations with gene expression in the whole blood of more than 500 subjects from 3 racial/ethnic groups.ResultsWe identified a genome-wide significant admixture mapping peak at 18q21 in Latinos (P = 6.8 × 10-6), where Native American ancestry was associated with increased risk of asthma (odds ratio [OR], 1.20; 95% CI, 1.07-1.34; P = .002) and European ancestry was associated with protection (OR, 0.86; 95% CI, 0.77-0.96; P = .008). Our findings were replicated in an independent childhood asthma study in Latinos (P = 5.3 × 10-3, combined P = 2.6 × 10-7). Fine mapping of 18q21 in 1978 Latinos identified a significant association with multiple variants 5' of SMAD family member 2 (SMAD2) in Mexicans, whereas a single rare variant in the same window was the top association in Puerto Ricans. Low versus high SMAD2 blood expression was correlated with case status (13.4% lower expression; OR, 3.93; 95% CI, 2.12-7.28; P

Published
2019

32. Novel Common Genetic Susceptibility Loci for Colorectal Cancer

Author

Schmit, Stephanie L, Edlund, Christopher K, Schumacher, Fredrick R, Gong, Jian, Harrison, Tabitha A, Huyghe, Jeroen R, Qu, Chenxu, Melas, Marilena, Van Den Berg, David J, Wang, Hansong, Tring, Stephanie, Plummer, Sarah J, Albanes, Demetrius, Alonso, M Henar, Amos, Christopher I, Anton, Kristen, Aragaki, Aaron K, Arndt, Volker, Barry, Elizabeth L, Berndt, Sonja I, Bezieau, Stéphane, Bien, Stephanie, Bloomer, Amanda, Boehm, Juergen, Boutron-Ruault, Marie-Christine, Brenner, Hermann, Brezina, Stefanie, Buchanan, Daniel D, Butterbach, Katja, Caan, Bette J, Campbell, Peter T, Carlson, Christopher S, Castelao, Jose E, Chan, Andrew T, Chang-Claude, Jenny, Chanock, Stephen J, Cheng, Iona, Cheng, Ya-Wen, Chin, Lee Soo, Church, James M, Church, Timothy, Coetzee, Gerhard A, Cotterchio, Michelle, Correa, Marcia Cruz, Curtis, Keith R, Duggan, David, Easton, Douglas F, English, Dallas, Feskens, Edith JM, Fischer, Rocky, FitzGerald, Liesel M, Fortini, Barbara K, Fritsche, Lars G, Fuchs, Charles S, Gago-Dominguez, Manuela, Gala, Manish, Gallinger, Steven J, Gauderman, W James, Giles, Graham G, Giovannucci, Edward L, Gogarten, Stephanie M, Gonzalez-Villalpando, Clicerio, Gonzalez-Villalpando, Elena M, Grady, William M, Greenson, Joel K, Gsur, Andrea, Gunter, Marc, Haiman, Christopher A, Hampe, Jochen, Harlid, Sophia, Harju, John F, Hayes, Richard B, Hofer, Philipp, Hoffmeister, Michael, Hopper, John L, Huang, Shu-Chen, Huerta, Jose Maria, Hudson, Thomas J, Hunter, David J, Idos, Gregory E, Iwasaki, Motoki, Jackson, Rebecca D, Jacobs, Eric J, Jee, Sun Ha, Jenkins, Mark A, Jia, Wei-Hua, Jiao, Shuo, Joshi, Amit D, Kolonel, Laurence N, Kono, Suminori, Kooperberg, Charles, Krogh, Vittorio, Kuehn, Tilman, Küry, Sébastien, LaCroix, Andrea, Laurie, Cecelia A, Lejbkowicz, Flavio, Lemire, Mathieu, Lenz, Heinz-Josef, and Levine, David

Subjects
Prevention, Cancer, Digestive Diseases, Human Genome, Genetics, Clinical Research, Colo-Rectal Cancer, Aetiology, 2.1 Biological and endogenous factors, Case-Control Studies, Colorectal Neoplasms, Ethnicity, Follow-Up Studies, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Polymorphism, Single Nucleotide, Prognosis, United States, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

BackgroundPrevious genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk.MethodsWe conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided.ResultsThe discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0.ConclusionsThis study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.

Published
2019

34. Interactions between folate intake and genetic predictors of gene expression levels associated with colorectal cancer risk

Author

Haas, Cameron B., Su, Yu-Ru, Petersen, Paneen, Wang, Xiaoliang, Bien, Stephanie A., Lin, Yi, Albanes, Demetrius, Weinstein, Stephanie J., Jenkins, Mark A., Figueiredo, Jane C., Newcomb, Polly A., Casey, Graham, Le Marchand, Loic, Campbell, Peter T., Moreno, Victor, Potter, John D., Sakoda, Lori C., Slattery, Martha L., Chan, Andrew T., Li, Li, Giles, Graham G., Milne, Roger L., Gruber, Stephen B., Rennert, Gad, Woods, Michael O., Gallinger, Steven J., Berndt, Sonja, Hayes, Richard B., Huang, Wen-Yi, Wolk, Alicja, White, Emily, Nan, Hongmei, Nassir, Rami, Lindor, Noralane M., Lewinger, Juan P., Kim, Andre E., Conti, David, Gauderman, W. James, Buchanan, Daniel D., Peters, Ulrike, and Hsu, Li

Published
2022
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37. Multi-ancestry genome-wide gene–sleep interactions identify novel loci for blood pressure

Author

Wang, Heming, Noordam, Raymond, Cade, Brian E., Schwander, Karen, Winkler, Thomas W., Lee, Jiwon, Sung, Yun Ju, Bentley, Amy R., Manning, Alisa K., Aschard, Hugues, Kilpeläinen, Tuomas O., Ilkov, Marjan, Brown, Michael R., Horimoto, Andrea R., Richard, Melissa, Bartz, Traci M., Vojinovic, Dina, Lim, Elise, Nierenberg, Jovia L., Liu, Yongmei, Chitrala, Kumaraswamynaidu, Rankinen, Tuomo, Musani, Solomon K., Franceschini, Nora, Rauramaa, Rainer, Alver, Maris, Zee, Phyllis C., Harris, Sarah E., van der Most, Peter J., Nolte, Ilja M., Munroe, Patricia B., Palmer, Nicholette D., Kühnel, Brigitte, Weiss, Stefan, Wen, Wanqing, Hall, Kelly A., Lyytikäinen, Leo-Pekka, O’Connell, Jeff, Eiriksdottir, Gudny, Launer, Lenore J., de Vries, Paul S., Arking, Dan E., Chen, Han, Boerwinkle, Eric, Krieger, Jose E., Schreiner, Pamela J., Sidney, Stephen, Shikany, James M., Rice, Kenneth, Chen, Yii-Der Ida, Gharib, Sina A., Bis, Joshua C., Luik, Annemarie I., Ikram, M. Arfan, Uitterlinden, André G., Amin, Najaf, Xu, Hanfei, Levy, Daniel, He, Jiang, Lohman, Kurt K., Zonderman, Alan B., Rice, Treva K., Sims, Mario, Wilson, Gregory, Sofer, Tamar, Rich, Stephen S., Palmas, Walter, Yao, Jie, Guo, Xiuqing, Rotter, Jerome I., Biermasz, Nienke R., Mook-Kanamori, Dennis O., Martin, Lisa W., Barac, Ana, Wallace, Robert B., Gottlieb, Daniel J., Komulainen, Pirjo, Heikkinen, Sami, Mägi, Reedik, Milani, Lili, Metspalu, Andres, Starr, John M., Milaneschi, Yuri, Waken, R. J., Gao, Chuan, Waldenberger, Melanie, Peters, Annette, Strauch, Konstantin, Meitinger, Thomas, Roenneberg, Till, Völker, Uwe, Dörr, Marcus, Shu, Xiao-Ou, Mukherjee, Sutapa, Hillman, David R., Kähönen, Mika, Wagenknecht, Lynne E., Gieger, Christian, Grabe, Hans J., Zheng, Wei, Palmer, Lyle J., Lehtimäki, Terho, Gudnason, Vilmundur, Morrison, Alanna C., Pereira, Alexandre C., Fornage, Myriam, Psaty, Bruce M., van Duijn, Cornelia M., Liu, Ching-Ti, Kelly, Tanika N., Evans, Michele K., Bouchard, Claude, Fox, Ervin R., Kooperberg, Charles, Zhu, Xiaofeng, Lakka, Timo A., Esko, Tõnu, North, Kari E., Deary, Ian J., Snieder, Harold, Penninx, Brenda W. J. H., Gauderman, W. James, Rao, Dabeeru C., Redline, Susan, and van Heemst, Diana

Published
2021
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38. Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Author

Waage, Johannes, Standl, Marie, Curtin, John A, Jessen, Leon E, Thorsen, Jonathan, Tian, Chao, Schoettler, Nathan, The 23andMe Research Team, AAGC collaborators, Flores, Carlos, Abdellaoui, Abdel, Ahluwalia, Tarunveer S, Alves, Alexessander C, Amaral, Andre FS, Antó, Josep M, Arnold, Andreas, Barreto-Luis, Amalia, Baurecht, Hansjörg, van Beijsterveldt, Catharina EM, Bleecker, Eugene R, Bonàs-Guarch, Sílvia, Boomsma, Dorret I, Brix, Susanne, Bunyavanich, Supinda, Burchard, Esteban G, Chen, Zhanghua, Curjuric, Ivan, Custovic, Adnan, den Dekker, Herman T, Dharmage, Shyamali C, Dmitrieva, Julia, Duijts, Liesbeth, Ege, Markus J, Gauderman, W James, Georges, Michel, Gieger, Christian, Gilliland, Frank, Granell, Raquel, Gui, Hongsheng, Hansen, Torben, Heinrich, Joachim, Henderson, John, Hernandez-Pacheco, Natalia, Holt, Patrick, Imboden, Medea, Jaddoe, Vincent WV, Jarvelin, Marjo-Riitta, Jarvis, Deborah L, Jensen, Kamilla K, Jónsdóttir, Ingileif, Kabesch, Michael, Kaprio, Jaakko, Kumar, Ashish, Lee, Young-Ae, Levin, Albert M, Li, Xingnan, Lorenzo-Diaz, Fabian, Melén, Erik, Mercader, Josep M, Meyers, Deborah A, Myers, Rachel, Nicolae, Dan L, Nohr, Ellen A, Palviainen, Teemu, Paternoster, Lavinia, Pennell, Craig E, Pershagen, Göran, Pino-Yanes, Maria, Probst-Hensch, Nicole M, Rüschendorf, Franz, Simpson, Angela, Stefansson, Kari, Sunyer, Jordi, Sveinbjornsson, Gardar, Thiering, Elisabeth, Thompson, Philip J, Torrent, Maties, Torrents, David, Tung, Joyce Y, Wang, Carol A, Weidinger, Stephan, Weiss, Scott, Willemsen, Gonneke, Williams, L Keoki, Ober, Carole, Hinds, David A, Ferreira, Manuel A, Bisgaard, Hans, Strachan, David P, and Bønnelykke, Klaus

Subjects
Biological Sciences, Genetics, Human Genome, Allergic Rhinitis (Hay Fever), Prevention, Biotechnology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Allergens, Case-Control Studies, Genetic Loci, Genetic Predisposition to Disease, Genetic Variation, Genome, Human, Genome-Wide Association Study, HLA Antigens, Humans, Phenotype, Rhinitis, Allergic, Risk, 23andMe Research Team, AAGC collaborators, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis.

Published
2018

39. Supplementary Methods from Genome-Wide Gene–Environment Interaction Analyses to Understand the Relationship between Red Meat and Processed Meat Intake and Colorectal Cancer Risk

Author

Stern, Mariana C., primary, Sanchez Mendez, Joel, primary, Kim, Andre E., primary, Obón-Santacana, Mireia, primary, Moratalla-Navarro, Ferran, primary, Martín, Vicente, primary, Moreno, Victor, primary, Lin, Yi, primary, Bien, Stephanie A., primary, Qu, Conghui, primary, Su, Yu-Ru, primary, White, Emily, primary, Harrison, Tabitha A., primary, Huyghe, Jeroen R., primary, Tangen, Catherine M., primary, Newcomb, Polly A., primary, Phipps, Amanda I., primary, Thomas, Claire E., primary, Kawaguchi, Eric S., primary, Lewinger, Juan Pablo, primary, Morrison, John L., primary, Conti, David V., primary, Wang, Jun, primary, Thomas, Duncan C., primary, Platz, Elizabeth A., primary, Visvanathan, Kala, primary, Keku, Temitope O., primary, Newton, Christina C., primary, Um, Caroline Y., primary, Kundaje, Anshul, primary, Shcherbina, Anna, primary, Murphy, Neil, primary, Gunter, Marc J., primary, Dimou, Niki, primary, Papadimitriou, Nikos, primary, Bézieau, Stéphane, primary, van Duijnhoven, Franzel J.B., primary, Männistö, Satu, primary, Rennert, Gad, primary, Wolk, Alicja, primary, Hoffmeister, Michael, primary, Brenner, Hermann, primary, Chang-Claude, Jenny, primary, Tian, Yu, primary, Le Marchand, Loïc, primary, Cotterchio, Michelle, primary, Tsilidis, Konstantinos K., primary, Bishop, D. Timothy, primary, Melaku, Yohannes Adama, primary, Lynch, Brigid M., primary, Buchanan, Daniel D., primary, Ulrich, Cornelia M., primary, Ose, Jennifer, primary, Peoples, Anita R., primary, Pellatt, Andrew J., primary, Li, Li, primary, Devall, Matthew A.M., primary, Campbell, Peter T., primary, Albanes, Demetrius, primary, Weinstein, Stephanie J., primary, Berndt, Sonja I., primary, Gruber, Stephen B., primary, Ruiz-Narvaez, Edward, primary, Song, Mingyang, primary, Joshi, Amit D., primary, Drew, David A., primary, Petrick, Jessica L., primary, Chan, Andrew T., primary, Giannakis, Marios, primary, Peters, Ulrike, primary, Hsu, Li, primary, and Gauderman, W. James, primary

Published
2024
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40. Supplementary Table 2 from Genome-Wide Gene–Environment Interaction Analyses to Understand the Relationship between Red Meat and Processed Meat Intake and Colorectal Cancer Risk

Author

Stern, Mariana C., primary, Sanchez Mendez, Joel, primary, Kim, Andre E., primary, Obón-Santacana, Mireia, primary, Moratalla-Navarro, Ferran, primary, Martín, Vicente, primary, Moreno, Victor, primary, Lin, Yi, primary, Bien, Stephanie A., primary, Qu, Conghui, primary, Su, Yu-Ru, primary, White, Emily, primary, Harrison, Tabitha A., primary, Huyghe, Jeroen R., primary, Tangen, Catherine M., primary, Newcomb, Polly A., primary, Phipps, Amanda I., primary, Thomas, Claire E., primary, Kawaguchi, Eric S., primary, Lewinger, Juan Pablo, primary, Morrison, John L., primary, Conti, David V., primary, Wang, Jun, primary, Thomas, Duncan C., primary, Platz, Elizabeth A., primary, Visvanathan, Kala, primary, Keku, Temitope O., primary, Newton, Christina C., primary, Um, Caroline Y., primary, Kundaje, Anshul, primary, Shcherbina, Anna, primary, Murphy, Neil, primary, Gunter, Marc J., primary, Dimou, Niki, primary, Papadimitriou, Nikos, primary, Bézieau, Stéphane, primary, van Duijnhoven, Franzel J.B., primary, Männistö, Satu, primary, Rennert, Gad, primary, Wolk, Alicja, primary, Hoffmeister, Michael, primary, Brenner, Hermann, primary, Chang-Claude, Jenny, primary, Tian, Yu, primary, Le Marchand, Loïc, primary, Cotterchio, Michelle, primary, Tsilidis, Konstantinos K., primary, Bishop, D. Timothy, primary, Melaku, Yohannes Adama, primary, Lynch, Brigid M., primary, Buchanan, Daniel D., primary, Ulrich, Cornelia M., primary, Ose, Jennifer, primary, Peoples, Anita R., primary, Pellatt, Andrew J., primary, Li, Li, primary, Devall, Matthew A.M., primary, Campbell, Peter T., primary, Albanes, Demetrius, primary, Weinstein, Stephanie J., primary, Berndt, Sonja I., primary, Gruber, Stephen B., primary, Ruiz-Narvaez, Edward, primary, Song, Mingyang, primary, Joshi, Amit D., primary, Drew, David A., primary, Petrick, Jessica L., primary, Chan, Andrew T., primary, Giannakis, Marios, primary, Peters, Ulrike, primary, Hsu, Li, primary, and Gauderman, W. James, primary

Published
2024
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41. Supplementary Figure 4 from Genome-Wide Gene–Environment Interaction Analyses to Understand the Relationship between Red Meat and Processed Meat Intake and Colorectal Cancer Risk

Author

Stern, Mariana C., primary, Sanchez Mendez, Joel, primary, Kim, Andre E., primary, Obón-Santacana, Mireia, primary, Moratalla-Navarro, Ferran, primary, Martín, Vicente, primary, Moreno, Victor, primary, Lin, Yi, primary, Bien, Stephanie A., primary, Qu, Conghui, primary, Su, Yu-Ru, primary, White, Emily, primary, Harrison, Tabitha A., primary, Huyghe, Jeroen R., primary, Tangen, Catherine M., primary, Newcomb, Polly A., primary, Phipps, Amanda I., primary, Thomas, Claire E., primary, Kawaguchi, Eric S., primary, Lewinger, Juan Pablo, primary, Morrison, John L., primary, Conti, David V., primary, Wang, Jun, primary, Thomas, Duncan C., primary, Platz, Elizabeth A., primary, Visvanathan, Kala, primary, Keku, Temitope O., primary, Newton, Christina C., primary, Um, Caroline Y., primary, Kundaje, Anshul, primary, Shcherbina, Anna, primary, Murphy, Neil, primary, Gunter, Marc J., primary, Dimou, Niki, primary, Papadimitriou, Nikos, primary, Bézieau, Stéphane, primary, van Duijnhoven, Franzel J.B., primary, Männistö, Satu, primary, Rennert, Gad, primary, Wolk, Alicja, primary, Hoffmeister, Michael, primary, Brenner, Hermann, primary, Chang-Claude, Jenny, primary, Tian, Yu, primary, Le Marchand, Loïc, primary, Cotterchio, Michelle, primary, Tsilidis, Konstantinos K., primary, Bishop, D. Timothy, primary, Melaku, Yohannes Adama, primary, Lynch, Brigid M., primary, Buchanan, Daniel D., primary, Ulrich, Cornelia M., primary, Ose, Jennifer, primary, Peoples, Anita R., primary, Pellatt, Andrew J., primary, Li, Li, primary, Devall, Matthew A.M., primary, Campbell, Peter T., primary, Albanes, Demetrius, primary, Weinstein, Stephanie J., primary, Berndt, Sonja I., primary, Gruber, Stephen B., primary, Ruiz-Narvaez, Edward, primary, Song, Mingyang, primary, Joshi, Amit D., primary, Drew, David A., primary, Petrick, Jessica L., primary, Chan, Andrew T., primary, Giannakis, Marios, primary, Peters, Ulrike, primary, Hsu, Li, primary, and Gauderman, W. James, primary

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2024
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42. Data from Genome-Wide Gene–Environment Interaction Analyses to Understand the Relationship between Red Meat and Processed Meat Intake and Colorectal Cancer Risk

Author

Stern, Mariana C., primary, Sanchez Mendez, Joel, primary, Kim, Andre E., primary, Obón-Santacana, Mireia, primary, Moratalla-Navarro, Ferran, primary, Martín, Vicente, primary, Moreno, Victor, primary, Lin, Yi, primary, Bien, Stephanie A., primary, Qu, Conghui, primary, Su, Yu-Ru, primary, White, Emily, primary, Harrison, Tabitha A., primary, Huyghe, Jeroen R., primary, Tangen, Catherine M., primary, Newcomb, Polly A., primary, Phipps, Amanda I., primary, Thomas, Claire E., primary, Kawaguchi, Eric S., primary, Lewinger, Juan Pablo, primary, Morrison, John L., primary, Conti, David V., primary, Wang, Jun, primary, Thomas, Duncan C., primary, Platz, Elizabeth A., primary, Visvanathan, Kala, primary, Keku, Temitope O., primary, Newton, Christina C., primary, Um, Caroline Y., primary, Kundaje, Anshul, primary, Shcherbina, Anna, primary, Murphy, Neil, primary, Gunter, Marc J., primary, Dimou, Niki, primary, Papadimitriou, Nikos, primary, Bézieau, Stéphane, primary, van Duijnhoven, Franzel J.B., primary, Männistö, Satu, primary, Rennert, Gad, primary, Wolk, Alicja, primary, Hoffmeister, Michael, primary, Brenner, Hermann, primary, Chang-Claude, Jenny, primary, Tian, Yu, primary, Le Marchand, Loïc, primary, Cotterchio, Michelle, primary, Tsilidis, Konstantinos K., primary, Bishop, D. Timothy, primary, Melaku, Yohannes Adama, primary, Lynch, Brigid M., primary, Buchanan, Daniel D., primary, Ulrich, Cornelia M., primary, Ose, Jennifer, primary, Peoples, Anita R., primary, Pellatt, Andrew J., primary, Li, Li, primary, Devall, Matthew A.M., primary, Campbell, Peter T., primary, Albanes, Demetrius, primary, Weinstein, Stephanie J., primary, Berndt, Sonja I., primary, Gruber, Stephen B., primary, Ruiz-Narvaez, Edward, primary, Song, Mingyang, primary, Joshi, Amit D., primary, Drew, David A., primary, Petrick, Jessica L., primary, Chan, Andrew T., primary, Giannakis, Marios, primary, Peters, Ulrike, primary, Hsu, Li, primary, and Gauderman, W. James, primary

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2024
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44. Supplementary Table 1 from Genome-Wide Gene–Environment Interaction Analyses to Understand the Relationship between Red Meat and Processed Meat Intake and Colorectal Cancer Risk

Author

Stern, Mariana C., primary, Sanchez Mendez, Joel, primary, Kim, Andre E., primary, Obón-Santacana, Mireia, primary, Moratalla-Navarro, Ferran, primary, Martín, Vicente, primary, Moreno, Victor, primary, Lin, Yi, primary, Bien, Stephanie A., primary, Qu, Conghui, primary, Su, Yu-Ru, primary, White, Emily, primary, Harrison, Tabitha A., primary, Huyghe, Jeroen R., primary, Tangen, Catherine M., primary, Newcomb, Polly A., primary, Phipps, Amanda I., primary, Thomas, Claire E., primary, Kawaguchi, Eric S., primary, Lewinger, Juan Pablo, primary, Morrison, John L., primary, Conti, David V., primary, Wang, Jun, primary, Thomas, Duncan C., primary, Platz, Elizabeth A., primary, Visvanathan, Kala, primary, Keku, Temitope O., primary, Newton, Christina C., primary, Um, Caroline Y., primary, Kundaje, Anshul, primary, Shcherbina, Anna, primary, Murphy, Neil, primary, Gunter, Marc J., primary, Dimou, Niki, primary, Papadimitriou, Nikos, primary, Bézieau, Stéphane, primary, van Duijnhoven, Franzel J.B., primary, Männistö, Satu, primary, Rennert, Gad, primary, Wolk, Alicja, primary, Hoffmeister, Michael, primary, Brenner, Hermann, primary, Chang-Claude, Jenny, primary, Tian, Yu, primary, Le Marchand, Loïc, primary, Cotterchio, Michelle, primary, Tsilidis, Konstantinos K., primary, Bishop, D. Timothy, primary, Melaku, Yohannes Adama, primary, Lynch, Brigid M., primary, Buchanan, Daniel D., primary, Ulrich, Cornelia M., primary, Ose, Jennifer, primary, Peoples, Anita R., primary, Pellatt, Andrew J., primary, Li, Li, primary, Devall, Matthew A.M., primary, Campbell, Peter T., primary, Albanes, Demetrius, primary, Weinstein, Stephanie J., primary, Berndt, Sonja I., primary, Gruber, Stephen B., primary, Ruiz-Narvaez, Edward, primary, Song, Mingyang, primary, Joshi, Amit D., primary, Drew, David A., primary, Petrick, Jessica L., primary, Chan, Andrew T., primary, Giannakis, Marios, primary, Peters, Ulrike, primary, Hsu, Li, primary, and Gauderman, W. James, primary

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2024
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45. Supplementary Figure 1 from Genome-Wide Gene–Environment Interaction Analyses to Understand the Relationship between Red Meat and Processed Meat Intake and Colorectal Cancer Risk

Author

Stern, Mariana C., primary, Sanchez Mendez, Joel, primary, Kim, Andre E., primary, Obón-Santacana, Mireia, primary, Moratalla-Navarro, Ferran, primary, Martín, Vicente, primary, Moreno, Victor, primary, Lin, Yi, primary, Bien, Stephanie A., primary, Qu, Conghui, primary, Su, Yu-Ru, primary, White, Emily, primary, Harrison, Tabitha A., primary, Huyghe, Jeroen R., primary, Tangen, Catherine M., primary, Newcomb, Polly A., primary, Phipps, Amanda I., primary, Thomas, Claire E., primary, Kawaguchi, Eric S., primary, Lewinger, Juan Pablo, primary, Morrison, John L., primary, Conti, David V., primary, Wang, Jun, primary, Thomas, Duncan C., primary, Platz, Elizabeth A., primary, Visvanathan, Kala, primary, Keku, Temitope O., primary, Newton, Christina C., primary, Um, Caroline Y., primary, Kundaje, Anshul, primary, Shcherbina, Anna, primary, Murphy, Neil, primary, Gunter, Marc J., primary, Dimou, Niki, primary, Papadimitriou, Nikos, primary, Bézieau, Stéphane, primary, van Duijnhoven, Franzel J.B., primary, Männistö, Satu, primary, Rennert, Gad, primary, Wolk, Alicja, primary, Hoffmeister, Michael, primary, Brenner, Hermann, primary, Chang-Claude, Jenny, primary, Tian, Yu, primary, Le Marchand, Loïc, primary, Cotterchio, Michelle, primary, Tsilidis, Konstantinos K., primary, Bishop, D. Timothy, primary, Melaku, Yohannes Adama, primary, Lynch, Brigid M., primary, Buchanan, Daniel D., primary, Ulrich, Cornelia M., primary, Ose, Jennifer, primary, Peoples, Anita R., primary, Pellatt, Andrew J., primary, Li, Li, primary, Devall, Matthew A.M., primary, Campbell, Peter T., primary, Albanes, Demetrius, primary, Weinstein, Stephanie J., primary, Berndt, Sonja I., primary, Gruber, Stephen B., primary, Ruiz-Narvaez, Edward, primary, Song, Mingyang, primary, Joshi, Amit D., primary, Drew, David A., primary, Petrick, Jessica L., primary, Chan, Andrew T., primary, Giannakis, Marios, primary, Peters, Ulrike, primary, Hsu, Li, primary, and Gauderman, W. James, primary

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2024
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46. Supplementary Figure 2 from Genome-Wide Gene–Environment Interaction Analyses to Understand the Relationship between Red Meat and Processed Meat Intake and Colorectal Cancer Risk

Author

Stern, Mariana C., primary, Sanchez Mendez, Joel, primary, Kim, Andre E., primary, Obón-Santacana, Mireia, primary, Moratalla-Navarro, Ferran, primary, Martín, Vicente, primary, Moreno, Victor, primary, Lin, Yi, primary, Bien, Stephanie A., primary, Qu, Conghui, primary, Su, Yu-Ru, primary, White, Emily, primary, Harrison, Tabitha A., primary, Huyghe, Jeroen R., primary, Tangen, Catherine M., primary, Newcomb, Polly A., primary, Phipps, Amanda I., primary, Thomas, Claire E., primary, Kawaguchi, Eric S., primary, Lewinger, Juan Pablo, primary, Morrison, John L., primary, Conti, David V., primary, Wang, Jun, primary, Thomas, Duncan C., primary, Platz, Elizabeth A., primary, Visvanathan, Kala, primary, Keku, Temitope O., primary, Newton, Christina C., primary, Um, Caroline Y., primary, Kundaje, Anshul, primary, Shcherbina, Anna, primary, Murphy, Neil, primary, Gunter, Marc J., primary, Dimou, Niki, primary, Papadimitriou, Nikos, primary, Bézieau, Stéphane, primary, van Duijnhoven, Franzel J.B., primary, Männistö, Satu, primary, Rennert, Gad, primary, Wolk, Alicja, primary, Hoffmeister, Michael, primary, Brenner, Hermann, primary, Chang-Claude, Jenny, primary, Tian, Yu, primary, Le Marchand, Loïc, primary, Cotterchio, Michelle, primary, Tsilidis, Konstantinos K., primary, Bishop, D. Timothy, primary, Melaku, Yohannes Adama, primary, Lynch, Brigid M., primary, Buchanan, Daniel D., primary, Ulrich, Cornelia M., primary, Ose, Jennifer, primary, Peoples, Anita R., primary, Pellatt, Andrew J., primary, Li, Li, primary, Devall, Matthew A.M., primary, Campbell, Peter T., primary, Albanes, Demetrius, primary, Weinstein, Stephanie J., primary, Berndt, Sonja I., primary, Gruber, Stephen B., primary, Ruiz-Narvaez, Edward, primary, Song, Mingyang, primary, Joshi, Amit D., primary, Drew, David A., primary, Petrick, Jessica L., primary, Chan, Andrew T., primary, Giannakis, Marios, primary, Peters, Ulrike, primary, Hsu, Li, primary, and Gauderman, W. James, primary

Published
2024
Full Text
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47. Supplementary Figure 3 from Genome-Wide Gene–Environment Interaction Analyses to Understand the Relationship between Red Meat and Processed Meat Intake and Colorectal Cancer Risk

Author

Stern, Mariana C., primary, Sanchez Mendez, Joel, primary, Kim, Andre E., primary, Obón-Santacana, Mireia, primary, Moratalla-Navarro, Ferran, primary, Martín, Vicente, primary, Moreno, Victor, primary, Lin, Yi, primary, Bien, Stephanie A., primary, Qu, Conghui, primary, Su, Yu-Ru, primary, White, Emily, primary, Harrison, Tabitha A., primary, Huyghe, Jeroen R., primary, Tangen, Catherine M., primary, Newcomb, Polly A., primary, Phipps, Amanda I., primary, Thomas, Claire E., primary, Kawaguchi, Eric S., primary, Lewinger, Juan Pablo, primary, Morrison, John L., primary, Conti, David V., primary, Wang, Jun, primary, Thomas, Duncan C., primary, Platz, Elizabeth A., primary, Visvanathan, Kala, primary, Keku, Temitope O., primary, Newton, Christina C., primary, Um, Caroline Y., primary, Kundaje, Anshul, primary, Shcherbina, Anna, primary, Murphy, Neil, primary, Gunter, Marc J., primary, Dimou, Niki, primary, Papadimitriou, Nikos, primary, Bézieau, Stéphane, primary, van Duijnhoven, Franzel J.B., primary, Männistö, Satu, primary, Rennert, Gad, primary, Wolk, Alicja, primary, Hoffmeister, Michael, primary, Brenner, Hermann, primary, Chang-Claude, Jenny, primary, Tian, Yu, primary, Le Marchand, Loïc, primary, Cotterchio, Michelle, primary, Tsilidis, Konstantinos K., primary, Bishop, D. Timothy, primary, Melaku, Yohannes Adama, primary, Lynch, Brigid M., primary, Buchanan, Daniel D., primary, Ulrich, Cornelia M., primary, Ose, Jennifer, primary, Peoples, Anita R., primary, Pellatt, Andrew J., primary, Li, Li, primary, Devall, Matthew A.M., primary, Campbell, Peter T., primary, Albanes, Demetrius, primary, Weinstein, Stephanie J., primary, Berndt, Sonja I., primary, Gruber, Stephen B., primary, Ruiz-Narvaez, Edward, primary, Song, Mingyang, primary, Joshi, Amit D., primary, Drew, David A., primary, Petrick, Jessica L., primary, Chan, Andrew T., primary, Giannakis, Marios, primary, Peters, Ulrike, primary, Hsu, Li, primary, and Gauderman, W. James, primary

Published
2024
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48. Supplementary Figure 5 from Genome-Wide Gene–Environment Interaction Analyses to Understand the Relationship between Red Meat and Processed Meat Intake and Colorectal Cancer Risk

Author

Stern, Mariana C., primary, Sanchez Mendez, Joel, primary, Kim, Andre E., primary, Obón-Santacana, Mireia, primary, Moratalla-Navarro, Ferran, primary, Martín, Vicente, primary, Moreno, Victor, primary, Lin, Yi, primary, Bien, Stephanie A., primary, Qu, Conghui, primary, Su, Yu-Ru, primary, White, Emily, primary, Harrison, Tabitha A., primary, Huyghe, Jeroen R., primary, Tangen, Catherine M., primary, Newcomb, Polly A., primary, Phipps, Amanda I., primary, Thomas, Claire E., primary, Kawaguchi, Eric S., primary, Lewinger, Juan Pablo, primary, Morrison, John L., primary, Conti, David V., primary, Wang, Jun, primary, Thomas, Duncan C., primary, Platz, Elizabeth A., primary, Visvanathan, Kala, primary, Keku, Temitope O., primary, Newton, Christina C., primary, Um, Caroline Y., primary, Kundaje, Anshul, primary, Shcherbina, Anna, primary, Murphy, Neil, primary, Gunter, Marc J., primary, Dimou, Niki, primary, Papadimitriou, Nikos, primary, Bézieau, Stéphane, primary, van Duijnhoven, Franzel J.B., primary, Männistö, Satu, primary, Rennert, Gad, primary, Wolk, Alicja, primary, Hoffmeister, Michael, primary, Brenner, Hermann, primary, Chang-Claude, Jenny, primary, Tian, Yu, primary, Le Marchand, Loïc, primary, Cotterchio, Michelle, primary, Tsilidis, Konstantinos K., primary, Bishop, D. Timothy, primary, Melaku, Yohannes Adama, primary, Lynch, Brigid M., primary, Buchanan, Daniel D., primary, Ulrich, Cornelia M., primary, Ose, Jennifer, primary, Peoples, Anita R., primary, Pellatt, Andrew J., primary, Li, Li, primary, Devall, Matthew A.M., primary, Campbell, Peter T., primary, Albanes, Demetrius, primary, Weinstein, Stephanie J., primary, Berndt, Sonja I., primary, Gruber, Stephen B., primary, Ruiz-Narvaez, Edward, primary, Song, Mingyang, primary, Joshi, Amit D., primary, Drew, David A., primary, Petrick, Jessica L., primary, Chan, Andrew T., primary, Giannakis, Marios, primary, Peters, Ulrike, primary, Hsu, Li, primary, and Gauderman, W. James, primary

Published
2024
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49. Lessons Learned From Past Gene-Environment Interaction Successes.

Author

Ritz, Beate R, Chatterjee, Nilanjan, Garcia-Closas, Montserrat, Gauderman, W James, Pierce, Brandon L, Kraft, Peter, Tanner, Caroline M, Mechanic, Leah E, and McAllister, Kimberly

Subjects
Epidemiology, Health Sciences, Patient Safety, Genetics, Aetiology, 2.1 Biological and endogenous factors, Biomedical Research, Disease, Environmental Exposure, Gene-Environment Interaction, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Humans, Models, Biological, exposure, gene-environment, genome-wide association studies, interactions, metabolism genes, pathway genes, pharmacogenomics, Mathematical Sciences, Medical and Health Sciences
Abstract

Genetic and environmental factors are both known to contribute to susceptibility to complex diseases. Therefore, the study of gene-environment interaction (G×E) has been a focus of research for several years. In this article, select examples of G×E from the literature are described to highlight different approaches and underlying principles related to the success of these studies. These examples can be broadly categorized as studies of single metabolism genes, genes in complex metabolism pathways, ranges of exposure levels, functional approaches and model systems, and pharmacogenomics. Some studies illustrated the success of studying exposure metabolism for which candidate genes can be identified. Moreover, some G×E successes depended on the availability of high-quality exposure assessment and longitudinal measures, study populations with a wide range of exposure levels, and the inclusion of ethnically and geographically diverse populations. In several examples, large population sizes were required to detect G×Es. Other examples illustrated the impact of accurately defining scale of the interactions (i.e., additive or multiplicative). Last, model systems and functional approaches provided insights into G×E in several examples. Future studies may benefit from these lessons learned.

Published
2017

50. Current Challenges and New Opportunities for Gene-Environment Interaction Studies of Complex Diseases

Author

McAllister, Kimberly, Mechanic, Leah E, Amos, Christopher, Aschard, Hugues, Blair, Ian A, Chatterjee, Nilanjan, Conti, David, Gauderman, W James, Hsu, Li, Hutter, Carolyn M, Jankowska, Marta M, Kerr, Jacqueline, Kraft, Peter, Montgomery, Stephen B, Mukherjee, Bhramar, Papanicolaou, George J, Patel, Chirag J, Ritchie, Marylyn D, Ritz, Beate R, Thomas, Duncan C, Wei, Peng, Witte, John S, and participants, on behalf of workshop

Subjects
Epidemiology, Health Sciences, Cancer, Human Genome, Genetics, 2.2 Factors relating to the physical environment, 2.1 Biological and endogenous factors, Aetiology, Generic health relevance, Good Health and Well Being, Disease, Gene-Environment Interaction, Genetic Predisposition to Disease, Genome-Wide Association Study, High-Throughput Nucleotide Sequencing, Humans, Software, environmental exposure, gene-environment interaction, genome-wide association study, Mathematical Sciences, Medical and Health Sciences
Abstract

Recently, many new approaches, study designs, and statistical and analytical methods have emerged for studying gene-environment interactions (G×Es) in large-scale studies of human populations. There are opportunities in this field, particularly with respect to the incorporation of -omics and next-generation sequencing data and continual improvement in measures of environmental exposures implicated in complex disease outcomes. In a workshop called "Current Challenges and New Opportunities for Gene-Environment Interaction Studies of Complex Diseases," held October 17-18, 2014, by the National Institute of Environmental Health Sciences and the National Cancer Institute in conjunction with the annual American Society of Human Genetics meeting, participants explored new approaches and tools that have been developed in recent years for G×E discovery. This paper highlights current and critical issues and themes in G×E research that need additional consideration, including the improved data analytical methods, environmental exposure assessment, and incorporation of functional data and annotations.

Published
2017

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