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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. Polygenic risk scores point toward potential genetic mechanisms of type 2 myocardial infarction in people with HIV.

Author

Lee, Won, Cheng, Haoxiang, Whitney, Bridget, Nance, Robin, Britton, Sierra, Jordahl, Kristina, Lindstrom, Sara, Ruderman, Stephanie, Kitahata, Mari, Saag, Michael, Willig, Amanda, Burkholder, Greer, Eron, Joseph, Kovacic, Jason, Björkegren, Johan, Mathews, W, Cachay, Edward, Feinstein, Matthew, Budoff, Mathew, Hunt, Peter, Moore, Richard, Keruly, Jeanne, McCaul, Mary, Chander, Geetanjali, Webel, Allison, Mayer, Kenneth, Delaney, Joseph, Crane, Paul, Martinez, Claudia, Crane, Heidi, Hao, Ke, and Peter, Inga

Subjects
Energy metabolism, HIV, Polygenic risk score, Type 1 myocardial infarction, Type 2 myocardial infarction, Humans, Myocardial Infarction, Risk Factors, Anterior Wall Myocardial Infarction, HIV Infections, Myocardium
Abstract

BACKGROUND: People with human immunodeficiency virus (HIV) infection (PWH) are at higher risk of myocardial infarction (MI) than those without HIV. About half of MIs in PWH are type 2 (T2MI), resulting from mismatch between myocardial oxygen supply and demand, in contrast to type 1 MI (T1MI), which is due to primary plaque rupture or coronary thrombosis. Despite worse survival and rising incidence in the general population, evidence-based treatment recommendations for T2MI are lacking. We used polygenic risk scores (PRS) to explore genetic mechanisms of T2MI compared to T1MI in PWH. METHODS: We derived 115 PRS for MI-related traits in 9541 PWH enrolled in the Centers for AIDS Research Network of Integrated Clinical Systems cohort with adjudicated T1MI and T2MI. We applied multivariate logistic regression analyses to determine the association with T1MI and T2MI. Based on initial findings, we performed gene set enrichment analysis of the top variants composing PRS associated with T2MI. RESULTS: We found that T1MI was strongly associated with PRS for cardiovascular disease, lipid profiles, and metabolic traits. In contrast, PRS for alcohol dependence and cholecystitis, significantly enriched in energy metabolism pathways, were predictive of T2MI risk. The association remained after the adjustment for actual alcohol consumption. CONCLUSIONS: We demonstrate distinct genetic traits associated with T1MI and T2MI among PWH further highlighting their etiological differences and supporting the role of energy regulation in T2MI pathogenesis.

Published
2023

3. Epigenome-wide meta-analysis of BMI in nine cohorts: Examining the utility of epigenetically predicted BMI.

Author

Do, Whitney, Sun, Dianjianyi, Meeks, Karlijn, Dugué, Pierre-Antoine, Demerath, Ellen, Guan, Weihua, Li, Shengxu, Chen, Wei, Milne, Roger, Adeyemo, Abedowale, Agyemang, Charles, Nassir, Rami, Manson, JoAnn, Hou, Lifang, Horvath, Steve, Assimes, Themistocles, Bhatti, Parveen, Jordahl, Kristina, Baccarelli, Andrea, Smith, Alicia, Staimez, Lisa, Stein, Aryeh, Whitsel, Eric, Narayan, K, Conneely, Karen, and Shadyab, Aladdin

Subjects
BMI, DNA methylation, adiposity, epigenome-wide association study, epigenomics, metabolic disease, obesity, prediction, Humans, Female, Body Mass Index, Epigenome, Epigenesis, Genetic, Obesity, Cholesterol, HDL, Genome-Wide Association Study, DNA Methylation, Epigenomics, Triglycerides, CpG Islands
Abstract

This study sought to examine the association between DNA methylation and body mass index (BMI) and the potential of BMI-associated cytosine-phosphate-guanine (CpG) sites to provide information about metabolic health. We pooled summary statistics from six trans-ethnic epigenome-wide association studies (EWASs) of BMI representing nine cohorts (n = 17,034), replicated these findings in the Womens Health Initiative (WHI, n = 4,822), and developed an epigenetic prediction score of BMI. In the pooled EWASs, 1,265 CpG sites were associated with BMI (p

Published
2023

4. Assessing the associations between known genetic variants and substance use in people with HIV in the United States.

Author

Haas, Cameron, Jordahl, Kristina, Nance, Robin, Whitney, Bridget, Wang, Lu, Delaney, Joseph, Ruderman, Stephanie, Jia, Tongqiu, Saag, Michael, Lee, Sulggi, Napravnik, Sonia, Jacobson, Jeffrey, Chander, Geetanjali, McCall, Elizabeth, Moore, Richard, Mayer, Kenneth, Mukherjee, Shubhabrata, Lee, Won, Crane, Paul, Crane, Heidi, Peter, Inga, Lindström, Sara, and Mathews, Christopher

Subjects
Humans, United States, Genome-Wide Association Study, Smoking, Alcohol Drinking, Substance-Related Disorders, Cannabis, Ethanol, HIV Infections
Abstract

BACKGROUND: The prevalence of substance use in people with HIV (PWH) in the United States is higher than in the general population and is an important driver of HIV-related outcomes. We sought to assess if previously identified genetic associations that contribute to substance use are also observed in a population of PWH. METHODS: We performed genome-wide association studies (GWAS) of alcohol, smoking, and cannabis use phenotypes in a multi-ancestry population of 7,542 PWH from the Center for AIDS Research Network of Integrated Clinical Systems (CNICS). We conducted multi-ancestry GWAS for individuals of African (n = 3,748), Admixed American (n = 1,334), and European (n = 2,460) ancestry. Phenotype data were self-reported and collected using patient reported outcomes (PROs) and three questions from AUDIT-C, an alcohol screening tool. We analyzed nine phenotypes: 1) frequency of alcohol consumption, 2) typical number of drinks on a day when drinking alcohol, 3) frequency of five or more alcoholic drinks in a 30-day period, 4) smoking initiation, 5) smoking cessation, 6) cigarettes per day, 7) cannabis use initiation, 8) cannabis use cessation, 9) frequency of cannabis use during the previous 30 days. For each phenotype we considered a) variants previously identified as associated with a substance use trait and b) novel associations. RESULTS: We observed evidence for effects of previously reported single nucleotide polymorphisms (SNPs) related to alcohol (rs1229984, p = 0.001), tobacco (rs11783093, p = 2.22E-4), and cannabis use (rs2875907, p = 0.005). We also report two novel loci (19p13.2, p = 1.3E-8; and 20p11.21, p = 2.1E-8) associated with cannabis use cessation. CONCLUSIONS: Our analyses contribute to understanding the genetic bases of substance use in a population with relatively higher rates of use compared to the general population.

Published
2023

5. 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

6. Methylation Subtypes of Primary Prostate Cancer Predict Poor Prognosis

Author

Wang, Xiaoyu, Jordahl, Kristina M, Zhu, Chenghao, Livingstone, Julie, Rhie, Suhn K, Wright, Jonathan L, Grady, William M, Boutros, Paul C, Stanford, Janet L, and Dai, James Y

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Human Genome, Prostate Cancer, Genetic Testing, Urologic Diseases, Genetics, Clinical Research, Cancer, Aging, Good Health and Well Being, Biomarkers, Tumor, Canada, Cohort Studies, DNA Methylation, Humans, Male, Prognosis, Prostatectomy, Prostatic Neoplasms, Medical and Health Sciences, Epidemiology, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundPatients with prostate cancer experience heterogeneous outcomes after radical prostatectomy. Genomic studies including The Cancer Genome Atlas (TCGA) have reported molecular signatures of prostate cancer, but few studies have assessed the prognostic effects of DNA methylation profiles.MethodsWe conducted the largest methylome subtyping analysis for primary prostate tumors to date, using methylome data from three patient populations: TCGA, a prostate cancer cohort study conducted at the Fred Hutchinson Cancer Research Center (FH; Seattle, WA), and the Canadian International Cancer Genome Consortium (ICGC) cohort. Four subtypes were detected in the TCGA dataset, then independently assigned to FH and ICGC cohort data. The identified methylation subtypes were assessed for association with cancer prognosis in the above three patient populations.ResultsUsing a set of hypermethylated CpG sites, four methylation subtypes were identified in TCGA. Compared with subtype 1, subtype 4 had an HR of 2.09 (P = 0.029) for biochemical recurrence (BCR) in TCGA patients. HRs of 2.76 (P = 0.002) for recurrence and 9.73 (P = 0.002) for metastatic-lethal (metastasis or prostate cancer-specific death) outcomes were observed in the FH cohort. A similar pattern of association was noted in the Canadian ICGC cohort, though HRs were not statistically significant.ConclusionsA hypermethylated subtype was associated with an increased hazard of recurrence and mortality in three studies with prostate tumor methylome data. Further molecular work is needed to understand the effect of methylation subtypes on cancer prognosis.ImpactThis study identified a DNA methylation subtype that was associated with worse prostate cancer prognosis after radical prostatectomy.

Published
2022

7. 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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8. Associations between DNA methylation and BMI vary by metabolic health status: a potential link to disparate cardiovascular outcomes

Author

Do, Whitney L, Nguyen, Steve, Yao, Jie, Guo, Xiuqing, Whitsel, Eric A, Demerath, Ellen, Rotter, Jerome I, Rich, Stephen S, Lange, Leslie, Ding, Jingzhong, Van Den Berg, David, Liu, Yongmei, Justice, Anne E, Guan, Weihua, Horvath, Steve, Assimes, Themistocles L, Bhatti, Parveen, Jordahl, Kristina, Shadyab, Aladdin, Valencia, Celina I, Stein, Aryeh D, Smith, Alicia, Staimez, Lisa R, Conneely, Karen, and Narayan, KM Venkat

Subjects
Biological Sciences, Genetics, Heart Disease - Coronary Heart Disease, Nutrition, Obesity, Cardiovascular, Aging, Clinical Research, Heart Disease, Atherosclerosis, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Aged, Body Mass Index, Cardiovascular Diseases, Cohort Studies, DNA Methylation, Female, Humans, Male, Metabolic Diseases, Middle Aged, DNA methylation, Metabolically healthy, Epigenetics, Clinical Sciences, Paediatrics and Reproductive Medicine
Abstract

BackgroundBody mass index (BMI), a well-known risk factor for poor cardiovascular outcomes, is associated with differential DNA methylation (DNAm). Similarly, metabolic health has also been associated with changes in DNAm. It is unclear how overall metabolic health outside of BMI may modify the relationship between BMI and methylation profiles, and what consequences this may have on downstream cardiovascular disease. The purpose of this study was to identify cytosine-phosphate-guanine (CpG) sites at which the association between BMI and DNAm could be modified by overall metabolic health.ResultsThe discovery study population was derived from three Women's Health Initiative (WHI) ancillary studies (n = 3977) and two Atherosclerosis Risk in Communities (ARIC) ancillary studies (n = 3520). Findings were validated in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort (n = 1200). Generalized linear models regressed methylation β values on the interaction between BMI and metabolic health Z score (BMI × MHZ) adjusted for BMI, MHZ, cell composition, chip number and location, study characteristics, top three ancestry principal components, smoking, age, ethnicity (WHI), and sex (ARIC). Among the 429,566 sites examined, differential associations between BMI × MHZ and DNAm were identified at 22 CpG sites (FDR q

Published
2021

9. Epigenome-wide association study of diet quality in the Women's Health Initiative and TwinsUK cohort.

Author

Do, Whitney L, Whitsel, Eric A, Costeira, Ricardo, Masachs, Olatz M, Le Roy, Caroline I, Bell, Jordana T, Staimez, Lisa R, Stein, Aryeh D, Smith, Alicia K, Horvath, Steve, Assimes, Themistocles L, Liu, Simin, Manson, JoAnn E, Shadyab, Aladdin H, Li, Yun, Hou, Lifang, Bhatti, Parveen, Jordahl, Kristina, Narayan, KM Venkat, and Conneely, Karen N

Subjects
Human Genome, Obesity, Prevention, Nutrition, Genetics, 2.2 Factors relating to the physical environment, Aetiology, Cancer, Cardiovascular, CpG Islands, DNA Methylation, Diet, Epigenesis, Genetic, Epigenome, Female, Genome-Wide Association Study, Humans, Proteins, Women's Health, diet quality, dietary epigenetics, EWAS, Women's Health Initiative, Women’s Health Initiative, Statistics, Public Health and Health Services, Epidemiology
Abstract

BackgroundDiet quality is a risk factor for chronic disease and mortality. Differential DNA methylation across the epigenome has been associated with chronic disease risk. Whether diet quality is associated with differential methylation is unknown. This study assessed whether diet quality was associated with differential DNA methylation measured across 445 548 loci in the Women's Health Initiative (WHI) and the TwinsUK cohort.DesignThe discovery cohort consisted of 4355 women from the WHI. The replication cohort consisted of 571 mono- and dizygotic twins from the TwinsUK cohort. DNA methylation was measured in whole blood using the Illumina Infinium HumanMethylation450 Beadchip. Diet quality was assessed using the Alternative Healthy Eating Index 2010 (AHEI-2010). A meta-analysis, stratified by study cohort, was performed using generalized linear models that regressed methylation on AHEI-2010, adjusting for cell composition, chip number and location, study characteristics, principal components of genetic relatedness, age, smoking status, race/ethnicity and body mass index (BMI). Statistical significance was defined as a false discovery rate < 0.05. Significant sites were tested for replication in the TwinsUK cohort, with significant replication defined by P

Published
2021

10. Polygenic risk scores point toward potential genetic mechanisms of type 2 myocardial infarction in people with HIV

Author

Lee, Won Jun, Cheng, Haoxiang, Whitney, Bridget M., Nance, Robin M., Britton, Sierra R., Jordahl, Kristina, Lindstrom, Sara, Ruderman, Stephanie A., Kitahata, Mari M., Saag, Michael S., Willig, Amanda L., Burkholder, Greer, Eron, Joseph J., Kovacic, Jason C., Björkegren, Johan L.M., Mathews, W. Christopher, Cachay, Edward, Feinstein, Matthew J., Budoff, Mathew, Hunt, Peter W., Moore, Richard D., Keruly, Jeanne, McCaul, Mary E., Chander, Geetanjali, Webel, Allison, Mayer, Kenneth H., Delaney, Joseph A., Crane, Paul K., Martinez, Claudia, Crane, Heidi M., Hao, Ke, and Peter, Inga

Published
2023
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11. 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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13. Two genome-wide interaction loci modify the association of nonsteroidal anti-inflammatory drugs with colorectal cancer

Author

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

Abstract

Regular, long-term aspirin use may act synergistically with genetic variants, particularly those in mechanistically relevant pathways, to confer a protective effect on colorectal cancer (CRC) risk. We leveraged pooled data from 52 clinical trial, cohort, and case-control studies that included 30,806 CRC cases and 41,861 controls of European ancestry to conduct a genome-wide interaction scan between regular aspirin/nonsteroidal anti-inflammatory drug (NSAID) use and imputed genetic variants. After adjusting for multiple comparisons, we identified statistically significant interactions between regular aspirin/NSAID use and variants in 6q24.1 (top hit rs72833769), which has evidence of influencing expression of TBC1D7 (a subunit of the TSC1-TSC2 complex, a key regulator of MTOR activity), and variants in 5p13.1 (top hit rs350047), which is associated with expression of PTGER4 (codes a cell surface receptor directly involved in the mode of action of aspirin). Genetic variants with functional impact may modulate the chemopreventive effect of regular aspirin use, and our study identifies putative previously unidentified targets for additional mechanistic interrogation.

Published
2024
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15. Data from A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk

Author

Aglago, Elom K., primary, Kim, Andre, primary, Lin, Yi, primary, Qu, Conghui, primary, Evangelou, Marina, primary, Ren, Yu, primary, Morrison, John, primary, Albanes, Demetrius, primary, Arndt, Volker, primary, Barry, Elizabeth L., primary, Baurley, James W., primary, Berndt, Sonja I., primary, Bien, Stephanie A., primary, Bishop, D. Timothy, primary, Bouras, Emmanouil, primary, Brenner, Hermann, primary, Buchanan, Daniel D., primary, Budiarto, Arif, primary, Carreras-Torres, Robert, primary, Casey, Graham, primary, Cenggoro, Tjeng Wawan, primary, Chan, Andrew T., primary, Chang-Claude, Jenny, primary, Chen, Xuechen, primary, Conti, David V., primary, Devall, Matthew, primary, Diez-Obrero, Virginia, primary, Dimou, Niki, primary, Drew, David, primary, Figueiredo, Jane C., primary, Gallinger, Steven, primary, Giles, Graham G., primary, Gruber, Stephen B., primary, Gsur, Andrea, primary, Gunter, Marc J., primary, Hampel, Heather, primary, Harlid, Sophia, primary, Hidaka, Akihisa, primary, Harrison, Tabitha A., primary, Hoffmeister, Michael, primary, Huyghe, Jeroen R., primary, Jenkins, Mark A., primary, Jordahl, Kristina, primary, Joshi, Amit D., primary, Kawaguchi, Eric S., primary, Keku, Temitope O., primary, Kundaje, Anshul, primary, Larsson, Susanna C., primary, Marchand, Loic Le, primary, Lewinger, Juan Pablo, primary, Li, Li, primary, Lynch, Brigid M., primary, Mahesworo, Bharuno, primary, Mandic, Marko, primary, Obón-Santacana, Mireia, primary, Moreno, Victor, primary, Murphy, Neil, primary, Nan, Hongmei, primary, Nassir, Rami, primary, Newcomb, Polly A., primary, Ogino, Shuji, primary, Ose, Jennifer, primary, Pai, Rish K., primary, Palmer, Julie R., primary, Papadimitriou, Nikos, primary, Pardamean, Bens, primary, Peoples, Anita R., primary, Platz, Elizabeth A., primary, Potter, John D., primary, Prentice, Ross L., primary, Rennert, Gad, primary, Ruiz-Narvaez, Edward, primary, Sakoda, Lori C., primary, Scacheri, Peter C., primary, Schmit, Stephanie L., primary, Schoen, Robert E., primary, Shcherbina, Anna, primary, Slattery, Martha L., primary, Stern, Mariana C., primary, Su, Yu-Ru, primary, Tangen, Catherine M., primary, Thibodeau, Stephen N., primary, Thomas, Duncan C., primary, Tian, Yu, primary, Ulrich, Cornelia M., primary, van Duijnhoven, Franzel JB, primary, Van Guelpen, Bethany, primary, Visvanathan, Kala, primary, Vodicka, Pavel, primary, Wang, Jun, primary, White, Emily, primary, Wolk, Alicja, primary, Woods, Michael O., primary, Wu, Anna H., primary, Zemlianskaia, Natalia, primary, Hsu, Li, primary, Gauderman, W. James, primary, Peters, Ulrike, primary, Tsilidis, Konstantinos K., primary, and Campbell, Peter T., primary

Published
2023
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16. Supplementary Data from A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk

Author

Aglago, Elom K., primary, Kim, Andre, primary, Lin, Yi, primary, Qu, Conghui, primary, Evangelou, Marina, primary, Ren, Yu, primary, Morrison, John, primary, Albanes, Demetrius, primary, Arndt, Volker, primary, Barry, Elizabeth L., primary, Baurley, James W., primary, Berndt, Sonja I., primary, Bien, Stephanie A., primary, Bishop, D. Timothy, primary, Bouras, Emmanouil, primary, Brenner, Hermann, primary, Buchanan, Daniel D., primary, Budiarto, Arif, primary, Carreras-Torres, Robert, primary, Casey, Graham, primary, Cenggoro, Tjeng Wawan, primary, Chan, Andrew T., primary, Chang-Claude, Jenny, primary, Chen, Xuechen, primary, Conti, David V., primary, Devall, Matthew, primary, Diez-Obrero, Virginia, primary, Dimou, Niki, primary, Drew, David, primary, Figueiredo, Jane C., primary, Gallinger, Steven, primary, Giles, Graham G., primary, Gruber, Stephen B., primary, Gsur, Andrea, primary, Gunter, Marc J., primary, Hampel, Heather, primary, Harlid, Sophia, primary, Hidaka, Akihisa, primary, Harrison, Tabitha A., primary, Hoffmeister, Michael, primary, Huyghe, Jeroen R., primary, Jenkins, Mark A., primary, Jordahl, Kristina, primary, Joshi, Amit D., primary, Kawaguchi, Eric S., primary, Keku, Temitope O., primary, Kundaje, Anshul, primary, Larsson, Susanna C., primary, Marchand, Loic Le, primary, Lewinger, Juan Pablo, primary, Li, Li, primary, Lynch, Brigid M., primary, Mahesworo, Bharuno, primary, Mandic, Marko, primary, Obón-Santacana, Mireia, primary, Moreno, Victor, primary, Murphy, Neil, primary, Nan, Hongmei, primary, Nassir, Rami, primary, Newcomb, Polly A., primary, Ogino, Shuji, primary, Ose, Jennifer, primary, Pai, Rish K., primary, Palmer, Julie R., primary, Papadimitriou, Nikos, primary, Pardamean, Bens, primary, Peoples, Anita R., primary, Platz, Elizabeth A., primary, Potter, John D., primary, Prentice, Ross L., primary, Rennert, Gad, primary, Ruiz-Narvaez, Edward, primary, Sakoda, Lori C., primary, Scacheri, Peter C., primary, Schmit, Stephanie L., primary, Schoen, Robert E., primary, Shcherbina, Anna, primary, Slattery, Martha L., primary, Stern, Mariana C., primary, Su, Yu-Ru, primary, Tangen, Catherine M., primary, Thibodeau, Stephen N., primary, Thomas, Duncan C., primary, Tian, Yu, primary, Ulrich, Cornelia M., primary, van Duijnhoven, Franzel JB, primary, Van Guelpen, Bethany, primary, Visvanathan, Kala, primary, Vodicka, Pavel, primary, Wang, Jun, primary, White, Emily, primary, Wolk, Alicja, primary, Woods, Michael O., primary, Wu, Anna H., primary, Zemlianskaia, Natalia, primary, Hsu, Li, primary, Gauderman, W. James, primary, Peters, Ulrike, primary, Tsilidis, Konstantinos K., primary, and Campbell, Peter T., primary

Published
2023
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17. Table 2 from A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk

Author

Aglago, Elom K., primary, Kim, Andre, primary, Lin, Yi, primary, Qu, Conghui, primary, Evangelou, Marina, primary, Ren, Yu, primary, Morrison, John, primary, Albanes, Demetrius, primary, Arndt, Volker, primary, Barry, Elizabeth L., primary, Baurley, James W., primary, Berndt, Sonja I., primary, Bien, Stephanie A., primary, Bishop, D. Timothy, primary, Bouras, Emmanouil, primary, Brenner, Hermann, primary, Buchanan, Daniel D., primary, Budiarto, Arif, primary, Carreras-Torres, Robert, primary, Casey, Graham, primary, Cenggoro, Tjeng Wawan, primary, Chan, Andrew T., primary, Chang-Claude, Jenny, primary, Chen, Xuechen, primary, Conti, David V., primary, Devall, Matthew, primary, Diez-Obrero, Virginia, primary, Dimou, Niki, primary, Drew, David, primary, Figueiredo, Jane C., primary, Gallinger, Steven, primary, Giles, Graham G., primary, Gruber, Stephen B., primary, Gsur, Andrea, primary, Gunter, Marc J., primary, Hampel, Heather, primary, Harlid, Sophia, primary, Hidaka, Akihisa, primary, Harrison, Tabitha A., primary, Hoffmeister, Michael, primary, Huyghe, Jeroen R., primary, Jenkins, Mark A., primary, Jordahl, Kristina, primary, Joshi, Amit D., primary, Kawaguchi, Eric S., primary, Keku, Temitope O., primary, Kundaje, Anshul, primary, Larsson, Susanna C., primary, Marchand, Loic Le, primary, Lewinger, Juan Pablo, primary, Li, Li, primary, Lynch, Brigid M., primary, Mahesworo, Bharuno, primary, Mandic, Marko, primary, Obón-Santacana, Mireia, primary, Moreno, Victor, primary, Murphy, Neil, primary, Nan, Hongmei, primary, Nassir, Rami, primary, Newcomb, Polly A., primary, Ogino, Shuji, primary, Ose, Jennifer, primary, Pai, Rish K., primary, Palmer, Julie R., primary, Papadimitriou, Nikos, primary, Pardamean, Bens, primary, Peoples, Anita R., primary, Platz, Elizabeth A., primary, Potter, John D., primary, Prentice, Ross L., primary, Rennert, Gad, primary, Ruiz-Narvaez, Edward, primary, Sakoda, Lori C., primary, Scacheri, Peter C., primary, Schmit, Stephanie L., primary, Schoen, Robert E., primary, Shcherbina, Anna, primary, Slattery, Martha L., primary, Stern, Mariana C., primary, Su, Yu-Ru, primary, Tangen, Catherine M., primary, Thibodeau, Stephen N., primary, Thomas, Duncan C., primary, Tian, Yu, primary, Ulrich, Cornelia M., primary, van Duijnhoven, Franzel JB, primary, Van Guelpen, Bethany, primary, Visvanathan, Kala, primary, Vodicka, Pavel, primary, Wang, Jun, primary, White, Emily, primary, Wolk, Alicja, primary, Woods, Michael O., primary, Wu, Anna H., primary, Zemlianskaia, Natalia, primary, Hsu, Li, primary, Gauderman, W. James, primary, Peters, Ulrike, primary, Tsilidis, Konstantinos K., primary, and Campbell, Peter T., primary

Published
2023
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18. Table 1 from A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk

Author

Aglago, Elom K., primary, Kim, Andre, primary, Lin, Yi, primary, Qu, Conghui, primary, Evangelou, Marina, primary, Ren, Yu, primary, Morrison, John, primary, Albanes, Demetrius, primary, Arndt, Volker, primary, Barry, Elizabeth L., primary, Baurley, James W., primary, Berndt, Sonja I., primary, Bien, Stephanie A., primary, Bishop, D. Timothy, primary, Bouras, Emmanouil, primary, Brenner, Hermann, primary, Buchanan, Daniel D., primary, Budiarto, Arif, primary, Carreras-Torres, Robert, primary, Casey, Graham, primary, Cenggoro, Tjeng Wawan, primary, Chan, Andrew T., primary, Chang-Claude, Jenny, primary, Chen, Xuechen, primary, Conti, David V., primary, Devall, Matthew, primary, Diez-Obrero, Virginia, primary, Dimou, Niki, primary, Drew, David, primary, Figueiredo, Jane C., primary, Gallinger, Steven, primary, Giles, Graham G., primary, Gruber, Stephen B., primary, Gsur, Andrea, primary, Gunter, Marc J., primary, Hampel, Heather, primary, Harlid, Sophia, primary, Hidaka, Akihisa, primary, Harrison, Tabitha A., primary, Hoffmeister, Michael, primary, Huyghe, Jeroen R., primary, Jenkins, Mark A., primary, Jordahl, Kristina, primary, Joshi, Amit D., primary, Kawaguchi, Eric S., primary, Keku, Temitope O., primary, Kundaje, Anshul, primary, Larsson, Susanna C., primary, Marchand, Loic Le, primary, Lewinger, Juan Pablo, primary, Li, Li, primary, Lynch, Brigid M., primary, Mahesworo, Bharuno, primary, Mandic, Marko, primary, Obón-Santacana, Mireia, primary, Moreno, Victor, primary, Murphy, Neil, primary, Nan, Hongmei, primary, Nassir, Rami, primary, Newcomb, Polly A., primary, Ogino, Shuji, primary, Ose, Jennifer, primary, Pai, Rish K., primary, Palmer, Julie R., primary, Papadimitriou, Nikos, primary, Pardamean, Bens, primary, Peoples, Anita R., primary, Platz, Elizabeth A., primary, Potter, John D., primary, Prentice, Ross L., primary, Rennert, Gad, primary, Ruiz-Narvaez, Edward, primary, Sakoda, Lori C., primary, Scacheri, Peter C., primary, Schmit, Stephanie L., primary, Schoen, Robert E., primary, Shcherbina, Anna, primary, Slattery, Martha L., primary, Stern, Mariana C., primary, Su, Yu-Ru, primary, Tangen, Catherine M., primary, Thibodeau, Stephen N., primary, Thomas, Duncan C., primary, Tian, Yu, primary, Ulrich, Cornelia M., primary, van Duijnhoven, Franzel JB, primary, Van Guelpen, Bethany, primary, Visvanathan, Kala, primary, Vodicka, Pavel, primary, Wang, Jun, primary, White, Emily, primary, Wolk, Alicja, primary, Woods, Michael O., primary, Wu, Anna H., primary, Zemlianskaia, Natalia, primary, Hsu, Li, primary, Gauderman, W. James, primary, Peters, Ulrike, primary, Tsilidis, Konstantinos K., primary, and Campbell, Peter T., primary

Published
2023
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20. A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk

Author

Aglago, Elom K., primary, Kim, Andre, additional, Lin, Yi, additional, Qu, Conghui, additional, Evangelou, Marina, additional, Ren, Yu, additional, Morrison, John, additional, Albanes, Demetrius, additional, Arndt, Volker, additional, Barry, Elizabeth L., additional, Baurley, James W., additional, Berndt, Sonja I., additional, Bien, Stephanie A., additional, Bishop, D. Timothy, additional, Bouras, Emmanouil, additional, Brenner, Hermann, additional, Buchanan, Daniel D., additional, Budiarto, Arif, additional, Carreras-Torres, Robert, additional, Casey, Graham, additional, Cenggoro, Tjeng Wawan, additional, Chan, Andrew T., additional, Chang-Claude, Jenny, additional, Chen, Xuechen, additional, Conti, David V., additional, Devall, Matthew, additional, Diez-Obrero, Virginia, additional, Dimou, Niki, additional, Drew, David, additional, Figueiredo, Jane C., additional, Gallinger, Steven, additional, Giles, Graham G., additional, Gruber, Stephen B., additional, Gsur, Andrea, additional, Gunter, Marc J., additional, Hampel, Heather, additional, Harlid, Sophia, additional, Hidaka, Akihisa, additional, Harrison, Tabitha A., additional, Hoffmeister, Michael, additional, Huyghe, Jeroen R., additional, Jenkins, Mark A., additional, Jordahl, Kristina, additional, Joshi, Amit D., additional, Kawaguchi, Eric S., additional, Keku, Temitope O., additional, Kundaje, Anshul, additional, Larsson, Susanna C., additional, Marchand, Loic Le, additional, Lewinger, Juan Pablo, additional, Li, Li, additional, Lynch, Brigid M., additional, Mahesworo, Bharuno, additional, Mandic, Marko, additional, Obón-Santacana, Mireia, additional, Moreno, Victor, additional, Murphy, Neil, additional, Nan, Hongmei, additional, Nassir, Rami, additional, Newcomb, Polly A., additional, Ogino, Shuji, additional, Ose, Jennifer, additional, Pai, Rish K., additional, Palmer, Julie R., additional, Papadimitriou, Nikos, additional, Pardamean, Bens, additional, Peoples, Anita R., additional, Platz, Elizabeth A., additional, Potter, John D., additional, Prentice, Ross L., additional, Rennert, Gad, additional, Ruiz-Narvaez, Edward, additional, Sakoda, Lori C., additional, Scacheri, Peter C., additional, Schmit, Stephanie L., additional, Schoen, Robert E., additional, Shcherbina, Anna, additional, Slattery, Martha L., additional, Stern, Mariana C., additional, Su, Yu-Ru, additional, Tangen, Catherine M., additional, Thibodeau, Stephen N., additional, Thomas, Duncan C., additional, Tian, Yu, additional, Ulrich, Cornelia M., additional, van Duijnhoven, Franzel JB, additional, Van Guelpen, Bethany, additional, Visvanathan, Kala, additional, Vodicka, Pavel, additional, Wang, Jun, additional, White, Emily, additional, Wolk, Alicja, additional, Woods, Michael O., additional, Wu, Anna H., additional, Zemlianskaia, Natalia, additional, Hsu, Li, additional, Gauderman, W. James, additional, Peters, Ulrike, additional, Tsilidis, Konstantinos K., additional, and Campbell, Peter T., additional

Published
2023
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21. A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk

Author

Aglago, Elom K., Kim, Andre, Lin, Yi, Qu, Conghui, Evangelou, Marina, Ren, Yu, Morrison, John, Albanes, Demetrius, Arndt, Volker, Barry, Elizabeth L., Baurley, James W., Berndt, Sonja I., Bien, Stephanie A., Bishop, D Timothy, Bouras, Emmanouil, Brenner, Hermann, Buchanan, Daniel D., Budiarto, Arif, Carreras-Torres, Robert, Casey, Graham, Cenggoro, Tjeng Wawan, Chan, Andrew T., Chang-Claude, Jenny, Chen, Xuechen, Conti, David V., Devall, Matthew, Diez-Obrero, Virginia, Dimou, Niki, Drew, David, Figueiredo, Jane C., Gallinger, Steven, Giles, Graham G., Gruber, Stephen B., Gsur, Andrea, Gunter, Marc J., Hampel, Heather, Harlid, Sophia, Hidaka, Akihisa, Harrison, Tabitha A., Hoffmeister, Michael, Huyghe, Jeroen R., Jenkins, Mark A., Jordahl, Kristina, Joshi, Amit D., Kawaguchi, Eric S., Keku, Temitope O., Kundaje, Anshul, Larsson, Susanna C., Marchand, Loic Le, Lewinger, Juan Pablo, Li, Li, Lynch, Brigid M., Mahesworo, Bharuno, Mandic, Marko, Obón-Santacana, Mireia, Moreno, Victor, Murphy, Neil, Nan, Hongmei, Nassir, Rami, Newcomb, Polly A., Ogino, Shuji, Ose, Jennifer, Pai, Rish K., Palmer, Julie R., Papadimitriou, Nikos, Pardamean, Bens, Peoples, Anita R., Platz, Elizabeth A., Potter, John D., Prentice, Ross L., Rennert, Gad, Ruiz-Narvaez, Edward, Sakoda, Lori C., Scacheri, Peter C., Schmit, Stephanie L., Schoen, Robert E., Shcherbina, Anna, Slattery, Martha L., Stern, Mariana C., Su, Yu-Ru, Tangen, Catherine M., Thibodeau, Stephen N., Thomas, Duncan C., Tian, Yu, Ulrich, Cornelia M., van Duijnhoven, Franzel Jb, van Guelpen, Bethany, Visvanathan, Kala, Vodicka, Pavel, Wang, Jun, White, Emily, Wolk, Alicja, Woods, Michael O., Wu, Anna H., Zemlianskaia, Natalia, Hsu, Li, Gauderman, W James, Peters, Ulrike, Tsilidis, Konstantinos K., Campbell, Peter T., Aglago, Elom K., Kim, Andre, Lin, Yi, Qu, Conghui, Evangelou, Marina, Ren, Yu, Morrison, John, Albanes, Demetrius, Arndt, Volker, Barry, Elizabeth L., Baurley, James W., Berndt, Sonja I., Bien, Stephanie A., Bishop, D Timothy, Bouras, Emmanouil, Brenner, Hermann, Buchanan, Daniel D., Budiarto, Arif, Carreras-Torres, Robert, Casey, Graham, Cenggoro, Tjeng Wawan, Chan, Andrew T., Chang-Claude, Jenny, Chen, Xuechen, Conti, David V., Devall, Matthew, Diez-Obrero, Virginia, Dimou, Niki, Drew, David, Figueiredo, Jane C., Gallinger, Steven, Giles, Graham G., Gruber, Stephen B., Gsur, Andrea, Gunter, Marc J., Hampel, Heather, Harlid, Sophia, Hidaka, Akihisa, Harrison, Tabitha A., Hoffmeister, Michael, Huyghe, Jeroen R., Jenkins, Mark A., Jordahl, Kristina, Joshi, Amit D., Kawaguchi, Eric S., Keku, Temitope O., Kundaje, Anshul, Larsson, Susanna C., Marchand, Loic Le, Lewinger, Juan Pablo, Li, Li, Lynch, Brigid M., Mahesworo, Bharuno, Mandic, Marko, Obón-Santacana, Mireia, Moreno, Victor, Murphy, Neil, Nan, Hongmei, Nassir, Rami, Newcomb, Polly A., Ogino, Shuji, Ose, Jennifer, Pai, Rish K., Palmer, Julie R., Papadimitriou, Nikos, Pardamean, Bens, Peoples, Anita R., Platz, Elizabeth A., Potter, John D., Prentice, Ross L., Rennert, Gad, Ruiz-Narvaez, Edward, Sakoda, Lori C., Scacheri, Peter C., Schmit, Stephanie L., Schoen, Robert E., Shcherbina, Anna, Slattery, Martha L., Stern, Mariana C., Su, Yu-Ru, Tangen, Catherine M., Thibodeau, Stephen N., Thomas, Duncan C., Tian, Yu, Ulrich, Cornelia M., van Duijnhoven, Franzel Jb, van Guelpen, Bethany, Visvanathan, Kala, Vodicka, Pavel, Wang, Jun, White, Emily, Wolk, Alicja, Woods, Michael O., Wu, Anna H., Zemlianskaia, Natalia, Hsu, Li, Gauderman, W James, Peters, Ulrike, Tsilidis, Konstantinos K., and Campbell, Peter T.

Abstract

Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer. SIGNIFICANCE: This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies.

Published
2023
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22. Genome-wide interaction study with smoking for colorectal cancer risk identifies novel genetic loci related to tumor suppression, inflammation, and immune response

Author

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

Abstract

BACKGROUND: Tobacco smoking is an established risk factor for colorectal cancer. However, genetically defined population subgroups may have increased susceptibility to smoking-related effects on colorectal cancer. METHODS: A genome-wide interaction scan was performed including 33,756 colorectal cancer cases and 44,346 controls from three genetic consortia. RESULTS: Evidence of an interaction was observed between smoking status (ever vs. never smokers) and a locus on 3p12.1 (rs9880919, P = 4.58 × 10-8), with higher associated risk in subjects carrying the GG genotype [OR, 1.25; 95% confidence interval (CI), 1.20-1.30] compared with the other genotypes (OR <1.17 for GA and AA). Among ever smokers, we observed interactions between smoking intensity (increase in 10 cigarettes smoked per day) and two loci on 6p21.33 (rs4151657, P = 1.72 × 10-8) and 8q24.23 (rs7005722, P = 2.88 × 10-8). Subjects carrying the rs4151657 TT genotype showed higher risk (OR, 1.12; 95% CI, 1.09-1.16) compared with the other genotypes (OR <1.06 for TC and CC). Similarly, higher risk was observed among subjects carrying the rs7005722 AA genotype (OR, 1.17; 95% CI, 1.07-1.28) compared with the other genotypes (OR <1.13 for AC and CC). Functional annotation revealed that SNPs in 3p12.1 and 6p21.33 loci were located in regulatory regions, and were associated with expression levels of nearby genes. Genetic models predicting gene expression revealed that smoking parameters were associated with lower colorectal cancer risk with higher expression levels of CADM2 (3p12.1) and ATF6B (6p21.33). CONCLUSIONS: Our study identified novel genetic loci that may modulate the risk for colorectal cancer of smoking status and intensity, linked to tumor suppression and immune response. IMPACT: These findings can guide potential prevention treatments.

Published
2023
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23. The Association of Epigenetic Age Acceleration and Multimorbidity at Age 90 in the Women's Health Initiative.

Author

Jain, Purva, Binder, Alexandra, Chen, Brian, Parada, Humberto, Gallo, Linda C, Alcaraz, John, Horvath, Steve, Bhatti, Parveen, Whitsel, Eric A, Jordahl, Kristina, Baccarelli, Andrea A, Hou, Lifang, Stewart, James D, Li, Yun, LaMonte, Michael J, Manson, JoAnn E, and LaCroix, Andrea Z

Subjects
COMORBIDITY, WOMEN'S health, OLDER women, POISSON regression, EPIGENETICS
Abstract

Background Epigenetic age acceleration (EAA), a measure of accelerated biological aging, has been associated with an increased risk of several age-related chronic conditions. This is the first study to prospectively examine the relationship between EAA and both multimorbidity count and a weighted multimorbidity score among long-lived postmenopausal women. Methods We included 1 951 women from the Women's Health Initiative who could have survived to age 90. EAA was estimated using the Horvath pan-tissue, Hannum, PhenoAge, and GrimAge "clocks." Twelve chronic conditions were included in the multimorbidity count. The multimorbidity score was weighted for each morbidity's relationship with mortality in the study population. Using mixed-effects Poisson and linear regression models that included baseline covariates associated with both EAA and multimorbidity, we estimated relative risks (RRs) and 95% confidence intervals (CIs) for the relationships between each EAA measure at the study baseline with both multimorbidity count and weighted multimorbidity score at age 90, respectively. Results For every one standard deviation increase in AgeAccelPheno, the rate of multimorbidity accumulation increased 6% (RR = 1.06; 95% CI = 1.01–1.12; p  = .025) and the multimorbidity score by 7% (RR = 1.07; 95% CI = 1.01–1.13; p  = .014) for women who survived to age 90. The results for a one standard deviation increase in AgeAccelHorvath, AgeAccelHannum, and AgeAccelGrim with multimorbidity accumulation and score were weaker compared to AgeAccelPheno, and the latter 2 did not reach statistical significance. Conclusion AgeAccelPheno and AgeAccelHannum may predict multimorbidity count and score at age 90 in older women and, thus, may be useful as a biomarker predictor of multimorbidity burden in the last decades of life. [ABSTRACT FROM AUTHOR]

Published
2023
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24. Supplementary Tables S6 and S7 from Germline Variants in Asporin Vary by Race, Modulate the Tumor Microenvironment, and Are Differentially Associated with Metastatic Prostate Cancer

Author

Hurley, Paula J., primary, Sundi, Debasish, primary, Shinder, Brian, primary, Simons, Brian W., primary, Hughes, Robert M., primary, Miller, Rebecca M., primary, Benzon, Benjamin, primary, Faraj, Sheila F., primary, Netto, George J., primary, Vergara, Ismael A., primary, Erho, Nicholas, primary, Davicioni, Elai, primary, Karnes, R. Jeffrey, primary, Yan, Guifang, primary, Ewing, Charles, primary, Isaacs, Sarah D., primary, Berman, David M., primary, Rider, Jennifer R., primary, Jordahl, Kristina M., primary, Mucci, Lorelei A., primary, Huang, Jessie, primary, An, Steven S., primary, Park, Ben H., primary, Isaacs, William B., primary, Marchionni, Luigi, primary, Ross, Ashley E., primary, and Schaeffer, Edward M., primary

Published
2023
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25. Supplementary Figure S1 from Germline Variants in Asporin Vary by Race, Modulate the Tumor Microenvironment, and Are Differentially Associated with Metastatic Prostate Cancer

Author

Hurley, Paula J., primary, Sundi, Debasish, primary, Shinder, Brian, primary, Simons, Brian W., primary, Hughes, Robert M., primary, Miller, Rebecca M., primary, Benzon, Benjamin, primary, Faraj, Sheila F., primary, Netto, George J., primary, Vergara, Ismael A., primary, Erho, Nicholas, primary, Davicioni, Elai, primary, Karnes, R. Jeffrey, primary, Yan, Guifang, primary, Ewing, Charles, primary, Isaacs, Sarah D., primary, Berman, David M., primary, Rider, Jennifer R., primary, Jordahl, Kristina M., primary, Mucci, Lorelei A., primary, Huang, Jessie, primary, An, Steven S., primary, Park, Ben H., primary, Isaacs, William B., primary, Marchionni, Luigi, primary, Ross, Ashley E., primary, and Schaeffer, Edward M., primary

Published
2023
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26. Genome-wide Interaction Study with Smoking for Colorectal Cancer Risk Identifies Novel Genetic Loci Related to Tumor Suppression, Inflammation, and Immune Response

Author

Carreras-Torres, Robert, primary, Kim, Andre E., additional, Lin, Yi, additional, Díez-Obrero, Virginia, additional, Bien, Stephanie A., additional, Qu, Conghui, additional, Wang, Jun, additional, Dimou, Niki, additional, Aglago, Elom K., additional, Albanes, Demetrius, additional, Arndt, Volker, additional, Baurley, James W., additional, Berndt, Sonja I., additional, Bézieau, Stéphane, additional, Bishop, D. Timothy, additional, Bouras, Emmanouil, additional, Brenner, Hermann, additional, Budiarto, Arif, additional, Campbell, Peter T., additional, Casey, Graham, additional, Chan, Andrew T., additional, Chang-Claude, Jenny, additional, Chen, Xuechen, additional, Conti, David V., additional, Dampier, Christopher H., additional, Devall, Matthew A.M., additional, Drew, David A., additional, Figueiredo, Jane C., additional, Gallinger, Steven, additional, Giles, Graham G., 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, Kawaguchi, Eric, additional, Keku, Temitope O., additional, Kundaje, Anshul, additional, Le Marchand, Loic, additional, Lewinger, Juan Pablo, additional, Li, Li, additional, Mahesworo, Bharuno, additional, Morrison, John L., additional, Murphy, Neil, additional, Nan, Hongmei, additional, Nassir, Rami, additional, Newcomb, Polly A., 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, Peoples, Anita R., additional, Pharoah, Paul D.P., 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, Shcherbina, Anna, additional, Slattery, Martha L., additional, Stern, Mariana C., additional, Su, Yu-Ru, additional, Tangen, Catherine M., additional, Thomas, Duncan C., additional, Tian, Yu, additional, Tsilidis, Konstantinos K., additional, Ulrich, Cornelia M., additional, van Duijnhoven, Fränzel J.B., additional, Van Guelpen, Bethany, additional, Visvanathan, Kala, additional, Vodicka, Pavel, additional, Cenggoro, Tjeng Wawan, additional, Weinstein, Stephanie J., additional, White, Emily, additional, Wolk, Alicja, additional, Woods, Michael O., additional, Hsu, Li, additional, Peters, Ulrike, additional, Moreno, Victor, additional, and Gauderman, W. James, additional

Published
2023
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28. Probing the diabetes and colorectal cancer relationship using gene – environment interaction analyses

Author

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

Published
2022
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29. Interpathologist concordance in the histological diagnosis of focal prostatic atrophy lesions, acute and chronic prostatitis, PIN, and prostate cancer

Author

Giunchi, Francesca, Jordahl, Kristina, Bollito, Enrico, Colecchia, Maurizio, Patriarca, Carlo, D’Errico, Antonietta, Vasuri, Francesco, Malvi, Deborah, Fornari, Alessandro, Bonetti, Luca Reggiani, Corti, Barbara, Papotti, Mauro, DeGiuli, Paolo, Loda, Massimo, Montironi, Rodolfo, Fiorentino, Michelangelo, and Rider, Jennifer R.

Published
2017
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30. Leukocyte Traits and Exposure to Ambient Particulate Matter Air Pollution in the Women's Health Initiative and Atherosclerosis Risk in Communities Study

Author

Gondalia, Rahul, Holliday, Katelyn M., Baldassari, Antoine, Justice, Anne E., Steward, James D., Liao, Duanping, Yanosky, Jeff D., Engel, Stephanie M., Jordahl, Kristina M., Bhatti, Parveen, Horvath, Steve, Assimes, Themistocles L., Pankow, James S., Demerath, Ellen W., Guan, Weihua, Fornage, Myriam, Bressler, Jan, North, Kari E., Conneely, Karen N., Li, Yun, Hou, Lifang, Baccarelli, Andrea A., and Whitsel, Eric A.

Subjects
United States. Environmental Protection Agency, Mortality -- North Carolina -- Minnesota -- California, Atherosclerosis -- Risk factors -- Health aspects, B cells -- Health aspects, Air pollution -- Health aspects, Women's health -- Health aspects, Information management -- Health aspects, Cardiovascular diseases -- Risk factors -- Health aspects, T cells -- Health aspects, Weather, Health, Women, Diseases, Pollution, Information accessibility, Environmental issues, Health
Abstract

Background: Inflammatory effects of ambient particulate matter (PM) air pollution exposures may underlie PM-related increases in cardiovascular disease risk and mortality, although evidence of PM-associated leukocytosis is inconsistent and largely based on small, cross-sectional, and/or unrepresentative study populations. Objectives: Our objective was to estimate PM-leukocyte associations among U.S. women and men in the Women's Health Initiative and Atherosclerosis Risk in Communities study (n =165,675). Methods: We based the PM-leukocyte estimations on up to four study visits per participant, at which peripheral blood leukocytes and geocoded address-specific concentrations of PM [less than or equal to] 10, [less than or equal to] 2.5, and 2.5-10 [micro]m in diameter ([PM.sub.10], [PM.sub.2.5], and [PM.sub.2.5]-10, respectively) were available. We multiply imputed missing data using chained equations and estimated PM-leukocyte count associations over daily to yearly PM exposure averaging periods using center-specific, linear, mixed, longitudinal models weighted for attrition and adjusted for sociodemographic, behavioral, meteorological, and geographic covariates. In a subset of participants with available data (n = 8,457), we also estimated PM-leukocyte proportion associations in compositional data analyses. Results: We found a 12 cells/[micro]L/ (95% confidence interval: -9, 33) higher leukocyte count, a 1.2% (0.6%, 1.8%) higher granulocyte proportion, and a -1.1% (-1.9%, -0.3%) lower [CD8.sup.+] T-cell proportion per 10-[micro]g/[m.sup.3] increase in 1-month mean [PM.sub.2.5]. However, shorter-duration [PM.sub.10] exposures were inversely and only modestly associated with leukocyte count. Discussion: The [PM.sub.2.5]-leukocyte estimates, albeit imprecise, suggest that among racially, ethnically, and environmentally diverse U.S. populations, sustained, ambient exposure to fine PM may induce subclinical, but epidemiologically important, inflammatory effects. https://doi.org/10.1289/EHP5360, Introduction Exposures to airborne particulate matter (PM) [less than or equal to] 10, [less than or equal to] 2.5 and between 2.5 and 10 [micro]m in diameter ([PM.sub.10], [PM.sub.2.5], and [...]

Published
2020
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31. The Association of Epigenetic Age Acceleration and Multimorbidity at Age 90 in the Women’s Health Initiative

Author

Jain, Purva, primary, Binder, Alexandra, additional, Chen, Brian, additional, Parada, Humberto, additional, Gallo, Linda C, additional, Alcaraz, John, additional, Horvath, Steve, additional, Bhatti, Parveen, additional, Whitsel, Eric A, additional, Jordahl, Kristina, additional, Baccarelli, Andrea A, additional, Hou, Lifang, additional, Stewart, James D, additional, Li, Yun, additional, La Monte, Michael J, additional, Manson, Jo Ann E, additional, and LaCroix, Andrea Z, additional

Published
2022
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32. Gaseous air pollutants and DNA methylation in a methylome-wide association study of an ethnically and environmentally diverse population of U.S. adults

Author

Holliday, Katelyn M., primary, Gondalia, Rahul, additional, Baldassari, Antoine, additional, Justice, Anne E., additional, Stewart, James D., additional, Liao, Duanping, additional, Yanosky, Jeff D., additional, Jordahl, Kristina M., additional, Bhatti, Parveen, additional, Assimes, Themistocles L., additional, Pankow, James S., additional, Guan, Weihua, additional, Fornage, Myriam, additional, Bressler, Jan, additional, North, Kari E., additional, Conneely, Karen N., additional, Li, Yun, additional, Hou, Lifang, additional, Vokonas, Pantel S., additional, Ward-Caviness, Cavin K., additional, Wilson, Rory, additional, Wolf, Kathrin, additional, Waldenberger, Melanie, additional, Cyrys, Josef, additional, Peters, Annette, additional, Boezen, H. Marike, additional, Vonk, Judith M., additional, Sayols-Baixeras, Sergi, additional, Lee, Mikyeong, additional, Baccarelli, Andrea A., additional, and Whitsel, Eric A., additional

Published
2022
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33. Epigenome-wide meta-analysis of BMI in nine cohorts: examining the utility of epigenetic BMI in predicting metabolic health

Author

Do, Whitney L., primary, Sun, Dianjianyi, additional, Meeks, Karlijn, additional, Dugue, Pierre-Antoine, additional, Demerath, Ellen, additional, Guan, Weihua, additional, Li, Shengxu, additional, Chen, Wei, additional, Milne, Roger, additional, Adeyemo, Abedowale, additional, Agyemang, Charles, additional, Nassir, Rami, additional, Manson, JoAnn, additional, Shadyab, Aladdin H, additional, Hou, Lifang, additional, Horvath, Steve, additional, Assimes, Themistocles L., additional, Bhatti, Parveen, additional, Jordahl, Kristina, additional, Baccarelli, Andrea, additional, Smith, Alicia, additional, Staimez, Lisa R., additional, Stein, Aryeh, additional, Whitsel, Eric A., additional, Venkat Narayan, K.M., additional, and Conneely, Karen, additional

Published
2022
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34. Analysis of Epigenetic Age Acceleration and Healthy Longevity Among Older US Women

Author

Jain, Purva, primary, Binder, Alexandra M., additional, Chen, Brian, additional, Parada, Humberto, additional, Gallo, Linda C., additional, Alcaraz, John, additional, Horvath, Steve, additional, Bhatti, Parveen, additional, Whitsel, Eric A., additional, Jordahl, Kristina, additional, Baccarelli, Andrea A., additional, Hou, Lifang, additional, Stewart, James D., additional, Li, Yun, additional, Justice, Jamie N., additional, and LaCroix, Andrea Z., additional

Published
2022
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35. Gaseous air pollutants and DNA methylation in a methylome-wide association study of an ethnically and environmentally diverse population of US adults

Author

Holliday, Katelyn M., Gondalia, Rahul, Baldassari, Antoine, Justice, Anne E., Stewart, James D., Liao, Duanping, Yanosky, Jeff D., Jordahl, Kristina M., Bhatti, Parveen, Assimes, Themistocles L., Pankow, James S., Guan, Weihua, Fornage, Myriam, Bressler, Jan, North, Kari E., Conneely, Karen N., Li, Yun, Hou, Lifang, Vokonas, Pantel S., Ward-Caviness, Cavin K., Wilson, Rory, Wolf, Kathrin, Waldenberger, Melanie, Cyrys, Josef, Peters, Annette, Boezen, H. Marike, Vonk, Judith M., Sayols-Baixeras, Sergi, Lee, Mikyeong, Baccarelli, Andrea A., Whitsel, Eric A., Holliday, Katelyn M., Gondalia, Rahul, Baldassari, Antoine, Justice, Anne E., Stewart, James D., Liao, Duanping, Yanosky, Jeff D., Jordahl, Kristina M., Bhatti, Parveen, Assimes, Themistocles L., Pankow, James S., Guan, Weihua, Fornage, Myriam, Bressler, Jan, North, Kari E., Conneely, Karen N., Li, Yun, Hou, Lifang, Vokonas, Pantel S., Ward-Caviness, Cavin K., Wilson, Rory, Wolf, Kathrin, Waldenberger, Melanie, Cyrys, Josef, Peters, Annette, Boezen, H. Marike, Vonk, Judith M., Sayols-Baixeras, Sergi, Lee, Mikyeong, Baccarelli, Andrea A., and Whitsel, Eric A.

Abstract

Epigenetic mechanisms may underlie air pollution-health outcome associations. We estimated gaseous air pollutant-DNA methylation (DNAm) associations using twelve subpopulations within Women's Health Initiative (WHI) and Atherosclerosis Risk in Communities (ARIC) cohorts (n = 8397; mean age 61.3 years; 83% female; 46% African-American, 46% European-American, 8% Hispanic/Latino). We used geocoded participant address-specific mean ambient carbon monoxide (CO), nitrogen oxides (NO2; NOx), ozone (O-3), and sulfur dioxide (SO2) concentrations estimated over the 2-, 7-, 28-, and 365-day periods before collection of blood samples used to generate Illumina 450 k array leukocyte DNAm measurements. We estimated methylome-wide, subpopulation-and race/ethnicity-stratified pollutant-DNAm associations in multi-level, linear mixed-effects models adjusted for sociodemographic, behavioral, meteorological, and technical covariates. We combined stratum-specific estimates in inverse variance-weighted meta-analyses and characterized significant associations (false discovery rate; FDR<0.05) at Cytosine-phosphate-Guanine (CpG) sites without among-strata heterogeneity (P-Cochran's Q > 0.05). We attempted replication in the Cooperative Health Research in Region of Augsburg (KORA) study and Normative Aging Study (NAS). We observed a -0.3 (95% CI: -0.4, -0.2) unit decrease in percent DNAm per interquartile range (IQR, 7.3 ppb) increase in 28-day mean NO2 concentration at cg01885635 (chromosome 3; regulatory region 290 bp upstream from ZNF621; FDR = 0.03). At intragenic sites cg21849932 (chromosome 20; LIME1; intron 3) and cg05353869 (chromosome 11; KLHL35; exon 2), we observed a -0.3 (95% CI: -0.4, -0.2) unit decrease (FDR = 0.04) and a 1.2 (95% CI: 0.7, 1.7) unit increase (FDR = 0.04), respectively, in percent DNAm per IQR (17.6 ppb) increase in 7-day mean ozone concentration. Results were not fully replicated in KORA and NAS. We identified three CpG sites potentially susceptible to gas

Published
2022
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36. Beyond GWAS of Colorectal Cancer : Putative Causal Variant for the 10q24.2 Region

Author

Jordahl, Kristina M., Shcherbina, Anna, Harlid, Sophia, van Guelpen, Bethany, Peters, Ulrike, Jordahl, Kristina M., Shcherbina, Anna, Harlid, Sophia, van Guelpen, Bethany, and Peters, Ulrike

Abstract

Background: Currently known associations between common genetic variants and colorectal cancer explain less than half of its heritability of 25%. As alcohol consumption has a J-shape association with colorectal cancer risk, nondrinking and heavy drinking are both risk factors for colorectal cancer. Methods: Individual-level data was pooled from the Colon Cancer Family Registry, Colorectal Transdisciplinary Study, and Genetics and Epidemiology of Colorectal Cancer Consortium to compare nondrinkers (≤1 g/day) and heavy drinkers (>28 g/day) with light-to-moderate drinkers (1-28 g/day) in GxE analyses. To improve power, we implemented joint 2df and 3df tests and a novel two-step method that modifies the weighted hypothesis testing framework. We prioritized putative causal variants by predicting allelic effects using support vector machine models. Results: For nondrinking as compared with light-to-moderate drinking, the hybrid two-step approach identified 13 significant SNPs with pairwise r2 > 0.9 in the 10q24.2/COX15 region. When stratified by alcohol intake, the A allele of lead SNP rs2300985 has a dose-response increase in risk of colorectal cancer as compared with the G allele in light-to-moderate drinkers [OR for GA genotype = 1.11; 95% confidence interval (CI), 1.06-1.17; OR for AA genotype = 1.22; 95% CI, 1.14-1.31], but not in nondrinkers or heavy drinkers. Among the correlated candidate SNPs in the 10q24.2/COX15 region, rs1318920 was predicted to disrupt an HNF4 transcription factor binding motif. Conclusions: Our study suggests that the association with colorectal cancer in 10q24.2/COX15 observed in genome-wide association study is strongest in nondrinkers. We also identified rs1318920 as the putative causal regulatory variant for the region. Impact: The study identifies multifaceted evidence of a possible functional effect for rs1318920.

Published
2022
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37. Genome-Wide Interaction Analysis of Genetic Variants With Menopausal Hormone Therapy for Colorectal Cancer Risk

Author

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

Published
2022
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38. Beyond GWAS of Colorectal Cancer: Evidence of Interaction with Alcohol Consumption and Putative Causal Variant for the 10q24.2 Region

Author

Jordahl, Kristina M., primary, Shcherbina, Anna, additional, Kim, Andre E., additional, Su, Yu-Ru, additional, Lin, Yi, additional, Wang, Jun, additional, Qu, Conghui, additional, Albanes, Demetrius, additional, Arndt, Volker, additional, Baurley, James W., additional, Berndt, Sonja I., additional, Bien, Stephanie A., additional, Bishop, D. Timothy, additional, Bouras, Emmanouil, additional, Brenner, Hermann, additional, Buchanan, Daniel D., additional, Budiarto, Arif, additional, Campbell, Peter T., additional, Carreras-Torres, Robert, additional, Casey, Graham, additional, Cenggoro, Tjeng Wawan, additional, Chan, Andrew T., additional, Conti, David V., additional, Dampier, Christopher H., additional, Devall, Matthew A., additional, Díez-Obrero, Virginia, additional, Dimou, Niki, additional, Drew, David A., additional, Figueiredo, Jane C., additional, Gallinger, Steven, additional, Giles, Graham G., additional, Gruber, Stephen B., additional, Gsur, Andrea, additional, Gunter, Marc J., additional, Hampel, Heather, additional, Harlid, Sophia, additional, Harrison, Tabitha A., additional, Hidaka, Akihisa, additional, Hoffmeister, Michael, additional, Huyghe, Jeroen R., additional, Jenkins, Mark A., additional, Joshi, Amit D., additional, Keku, Temitope O., additional, Larsson, Susanna C., additional, Le Marchand, Loic, additional, Lewinger, Juan Pablo, additional, Li, Li, additional, Mahesworo, Bharuno, additional, Moreno, Victor, additional, Morrison, John L., additional, Murphy, Neil, additional, Nan, Hongmei, additional, Nassir, Rami, additional, Newcomb, Polly A., 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, Peoples, Anita R., additional, Pharoah, Paul D.P., additional, Platz, Elizabeth A., additional, Potter, John D., additional, Prentice, Ross L., additional, Rennert, Gad, additional, Ruiz-Narvaez, Edward, additional, Sakoda, Lori C., additional, Scacheri, Peter C., additional, Schmit, Stephanie L., additional, Schoen, Robert E., additional, Slattery, Martha L., additional, Stern, Mariana C., additional, Tangen, Catherine M., additional, Thibodeau, Stephen N., additional, Thomas, Duncan C., additional, Tian, Yu, additional, Tsilidis, Konstantinos K., additional, Ulrich, Cornelia M., additional, van Duijnhoven, Franzel J.B., additional, Van Guelpen, Bethany, additional, Visvanathan, Kala, additional, Vodicka, Pavel, additional, White, Emily, additional, Wolk, Alicja, additional, Woods, Michael O., additional, Wu, Anna H., additional, Zemlianskaia, Natalia, additional, Chang-Claude, Jenny, additional, Gauderman, W. James, additional, Hsu, Li, additional, Kundaje, Anshul, additional, and Peters, Ulrike, additional

Published
2022
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39. Smoking Methylation Marks for Prediction of Urothelial Cancer Risk

Author

Yu, Chenglong, primary, Jordahl, Kristina M., additional, Bassett, Julie K., additional, Joo, Jihoon Eric, additional, Wong, Ee Ming, additional, Brinkman, Maree T., additional, Schmidt, Daniel F., additional, Bolton, Damien M., additional, Makalic, Enes, additional, Brasky, Theodore M., additional, Shadyab, Aladdin H., additional, Tinker, Lesley F., additional, Longano, Anthony, additional, Hopper, John L., additional, English, Dallas R., additional, Milne, Roger L., additional, Bhatti, Parveen, additional, Southey, Melissa C., additional, Giles, Graham G., additional, and Dugué, Pierre-Antoine, additional

Published
2021
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41. Epigenetically mediated electrocardiographic manifestations of sub-chronic exposures to ambient particulate matter air pollution in the Women's Health Initiative and Atherosclerosis Risk in Communities Study

Author

Gondalia, Rahul, primary, Baldassari, Antoine, additional, Holliday, Katelyn M., additional, Justice, Anne E., additional, Stewart, James D., additional, Liao, Duanping, additional, Yanosky, Jeff D., additional, Engel, Stephanie M., additional, Sheps, David, additional, Jordahl, Kristina M., additional, Bhatti, Parveen, additional, Horvath, Steve, additional, Assimes, Themistocles L., additional, Demerath, Ellen W., additional, Guan, Weihua, additional, Fornage, Myriam, additional, Bressler, Jan, additional, North, Kari E., additional, Conneely, Karen N., additional, Li, Yun, additional, Hou, Lifang, additional, Baccarelli, Andrea A., additional, and Whitsel, Eric A., additional

Published
2021
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42. Abstract 815: Genome-wide gene-calcium interaction in relation to colorectal cancer risk

Author

Díez-Obrero, Virginia, primary, van Duijnhoven, Fränzel, additional, Kim, Andre E., additional, Baurley, James, additional, Campbell, Peter T., additional, Carreras-Torres, Robert, additional, Chang-Claude, Jenny, additional, Conti, David V., additional, Jenab, Mazda, additional, Hsu, Li, additional, Jordahl, Kristina M., additional, Lewinger, Juan Pablo, additional, Lin, Yi, additional, Newcomb, Polly A., additional, Obón-Santacana, Mireia, additional, Bens, Pardamean, additional, Anita, Peoples, additional, Qu, Conghui, additional, Ruiz-Narvaez, Edward, additional, Tian, Yu, additional, Tsilidis, Kostas, additional, Casey, Graham, additional, Peters, Ulrike, additional, Gauderman, James W., additional, and Moreno, Victor, additional

Published
2021
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45. Additional file 1 of Associations between DNA methylation and BMI vary by metabolic health status: a potential link to disparate cardiovascular outcomes

Author

Do, Whitney L., Nguyen, Steve, Yao, Jie, Guo, Xiuqing, Whitsel, Eric A., Demerath, Ellen, Rotter, Jerome I., Rich, Stephen S., Lange, Leslie, Ding, Jingzhong, Van Den Berg, David, Liu, Yongmei, Justice, Anne E., Guan, Weihua, Horvath, Steve, Assimes, Themistocles L., Bhatti, Parveen, Jordahl, Kristina, Shadyab, Aladdin, Valencia, Celina I., Stein, Aryeh D., Smith, Alicia, Staimez, Lisa R., Conneely, Karen, and Narayan, K. M. Venkat

Abstract

Additional file 1. Supplemental Figures 1-16. Supplemental Tables 1-6.

Published
2021
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46. Methylation Subtypes of Primary Prostate Cancer Predict Poor Prognosis.

Author

Xiaoyu Wang, Jordahl, Kristina M., Chenghao Zhu, Livingstone, Julie, Rhie, Suhn K., Wright, Jonathan L., Grady, William M., Boutros, Paul C., Stanford, Janet L., and Dai, James Y.

Abstract

Background: Patients with prostate cancer experience heterogeneous outcomes after radical prostatectomy. Genomic studies including The Cancer Genome Atlas (TCGA) have reported molecular signatures of prostate cancer, but few studies have assessed the prognostic effects of DNA methylation profiles. Methods: We conducted the largest methylome subtyping analysis for primary prostate tumors to date, using methylome data from three patient populations: TCGA, a prostate cancer cohort study conducted at the Fred Hutchinson Cancer Research Center (FH; Seattle, WA), and the Canadian International Cancer Genome Consortium (ICGC) cohort. Four subtypes were detected in the TCGA dataset, then independently assigned to FH and ICGC cohort data. The identified methylation subtypes were assessed for association with cancer prognosis in the above three patient populations. Results: Using a set of hypermethylated CpG sites, four methylation subtypes were identified in TCGA. Compared with subtype 1, subtype 4 had an HR of 2.09 (P = 0.029) for biochemical recurrence (BCR) in TCGA patients. HRs of 2.76 (P = 0.002) for recurrence and 9.73 (P = 0.002) for metastatic-lethal (metastasis or prostate cancer-specific death) outcomes were observed in the FH cohort. A similar pattern of association was noted in the Canadian ICGC cohort, though HRs were not statistically significant. Conclusions: A hypermethylated subtype was associated with an increased hazard of recurrence and mortality in three studies with prostate tumor methylome data. Further molecular work is needed to understand the effect of methylation subtypes on cancer prognosis. Impact: This study identified a DNA methylation subtype that was associated with worse prostate cancer prognosis after radical prostatectomy. [ABSTRACT FROM AUTHOR]

Published
2022
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47. A polymorphism in the promoter of FRAS1 is a candidate SNP associated with metastatic prostate cancer

Author

Wang, Victoria, primary, Geybels, Milan S., additional, Jordahl, Kristina M., additional, Gerke, Travis, additional, Hamid, Anis, additional, Penney, Kathryn L., additional, Markt, Sarah C., additional, Freedman, Matthew, additional, Pomerantz, Mark, additional, Lee, Gwo‐Shu M., additional, Rana, Huma, additional, Börnigen, Daniela, additional, Rebbeck, Timothy R., additional, Huttenhower, Curtis, additional, Eeles, Ros A., additional, Stanford, Janet L., additional, Consortium, Practical, additional, Berndt, Sonja I., additional, Claessens, Frank, additional, Sørensen, Karina D., additional, Park, Jong Y., additional, Vega, Ana, additional, Usmani, Nawaid, additional, Mucci, Lorelei, additional, and Sweeney, Christopher J., additional

Published
2021
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48. Epigenome-wide association study of diet quality in the Women’s Health Initiative and TwinsUK cohort

Author

Do, Whitney L, primary, Whitsel, Eric A, additional, Costeira, Ricardo, additional, Masachs, Olatz M, additional, Le Roy, Caroline I, additional, Bell, Jordana T, additional, Staimez, Lisa R, additional, Stein, Aryeh D, additional, Smith, Alicia K, additional, Horvath, Steve, additional, Assimes, Themistocles L, additional, Liu, Simin, additional, Manson, JoAnn E, additional, Shadyab, Aladdin H, additional, Li, Yun, additional, Hou, Lifang, additional, Bhatti, Parveen, additional, Jordahl, Kristina, additional, Narayan, K M Venkat, additional, and Conneely, Karen N, additional

Published
2020
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