Article
Multidisciplinary Sciences
Mina-A Jhun, Michael Mendelson, Rory Wilson, Rahul Gondalia, Roby Joehanes, Elias Salfati, Xiaoping Zhao, Kim Valeska Emilie Braun, Anh Nguyet Do, Asa K. Hedman, Tao Zhang, Elena Carnero-Montoro, Jincheng Shen, Traci M. Bartz, Jennifer A. Brody, May E. Montasser, Jeff R. O'Connell, Chen Yao, Rui Xia, Eric Boerwinkle, Megan Grove, Weihua Guan, Pfeiffer Liliane, Paula Singmann, Martina Mueller-Nurasyid, Thomas Meitinger, Christian Gieger, Annette Peters, Wei Zhao, Erin B. Ware, Jennifer A. Smith, Klodian Dhana, Joyce van Meurs, Andre Uitterlinden, Mohammad Arfan Ikram, Mohsen Ghanbari, Deugi Zhi, Stefan Gustafsson, Lars Lind, Shengxu Li, Dianjianyi Sun, Tim D. Spector, Yii-der Ida Chen, Coleen Damcott, Alan R. Shuldiner, Devin M. Absher, Steve Horvath, Philip S. Tsao, Sharon Kardia, Bruce M. Psaty, Nona Sotoodehnia, Jordana T. Bell, Erik Ingelsson, Wei Chen, Abbas Dehghan, Donna K. Arnett, Melanie Waldenberger, Lifang Hou, Eric A. Whitsel, Andrea Baccarelli, Daniel Levy, Myriam Fornage, Marguerite R. Irvin, Themistocles L. Assimes
Summary: The study reveals strong and consistent associations between DNA methylation and blood lipid levels across multiple racial/ethnic groups, with specific and common CpG-lipid trait associations identified through a large-scale multi-ethnic epigenome-wide association study.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Xiaomeng Zhang, Xue Li, Yazhou He, Philip J. Law, Susan M. Farrington, Harry Campbell, Ian P. M. Tomlinson, Richard S. Houlston, Malcolm G. Dunlop, Maria Timofeeva, Evropi Theodoratou
Summary: The study found that benign colorectal neoplasms share genetic aetiology with CRC, and that CRC genetic predisposition is associated with diverticular disease.
BRITISH JOURNAL OF CANCER
(2022)
Article
Multidisciplinary Sciences
Jing Su, Kai Xu, Zirong Li, Yuan Hu, Zhongli Hu, Xingfei Zheng, Shufeng Song, Zhonghai Tang, Lanzhi Li
Summary: Rice yield is mainly controlled by minor-effect loci, and selecting quantitative trait locus/gene affecting component traits can further enhance yield. Loci for GPP or TP primarily have a positive genetic effect on yield, while loci for KGW have different effects; in addition, TP has a greater impact on yield than KGW and GPP.
SCIENTIFIC REPORTS
(2021)
Review
Biochemistry & Molecular Biology
Frederick J. Boehm, Xiang Zhou
Summary: Genome-wide association studies have provided numerous associations for common diseases and complex traits. Mendelian randomization methods, utilizing SNP associations, help uncover causal relationships between complex traits. The availability of GWAS summary statistics has motivated the development of new Mendelian randomization methods with relaxed causality assumptions, offering opportunities for robust biological discoveries.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Immunology
Shan Lin, Xueyan Mao, Wanmei He
Summary: This genetic data analysis study using Mendelian Randomization (MR) framework explores the causal relationship between cytokines and sepsis. The study found that genetically predicted levels of RANTES, basic-FGF, and beta-NGF are associated with altered sepsis risk.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Xuexian Fang, Xinhui Wang, Zijun Song, Dan Han, Xiangju Yin, Bingqing Liu, Luyi Chen, Ronghua Zhang, Fuzhi Lian, Xinbing Sui
Summary: A study using Mendelian randomization found a significant increase in the risk of pancreatic and esophageal cancer in adults due to childhood obesity, while a negative correlation was observed with throat and breast cancer risk. Maintaining a healthy weight during childhood and adolescence should be emphasized to prevent future cancer risks.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Public, Environmental & Occupational Health
Maria C. Magnus, Maria Carolina Borges, Abigail Fraser, Deborah A. Lawlor
Summary: The age at natural menopause is associated with various health-related traits. This study conducted a Mendelian randomization phenome-wide association study to investigate these associations. The findings suggest that younger age at natural menopause may have potential causal effects on a range of health-related traits.
EUROPEAN JOURNAL OF EPIDEMIOLOGY
(2022)
Article
Medicine, General & Internal
Chunyang Li, Yilong Chen, Yi Chen, Zhiye Ying, Yao Hu, Yalan Kuang, Huazhen Yang, Huan Song, Xiaoxi Zeng
Summary: This study aimed to identify novel associations between irritable bowel syndrome (IBS) and a broad range of outcomes. Using a genome-wide association study (GWAS) and polygenic risk score (PRS) analysis, the study found five diseases associated with genetically predicted IBS. Causal associations were observed in females only, not males.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Endocrinology & Metabolism
Aiyong Cui, Peilun Xiao, Zhiqiang Fan, Jinlai Lei, Shuang Han, Danlong Zhang, Xing Wei, Pengfei Wang, Yan Zhuang
Summary: This study investigated the causal association between NAFLD and osteoporosis using a bidirectional two-sample Mendelian analysis. The results showed a causal relationship between NAFLD and osteoporosis, but no causal effect of osteoporosis on NAFLD. Furthermore, NAFLD did not have a causal effect on fracture and fall risk.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Medicine, General & Internal
Shuai Yuan, Jing Sun, Ying Lu, Fengzhe Xu, Doudou Li, Fangyuan Jiang, Zhongxiao Wan, Xue Li, Li-Qiang Qin, Susanna C. Larsson
Summary: Through Mendelian randomization analysis and two-sample MR analysis, we have identified associations between milk consumption and various diseases, including cataract, hypercholesterolemia, and anal and rectal polyps. The systematic review also found that genetically predicted milk consumption was inversely associated with asthma, hay fever, multiple sclerosis, colorectal cancer, and Alzheimer's disease, and positively associated with Parkinson's disease, renal cell carcinoma, metabolic syndrome, overweight, and obesity.
Article
Immunology
Guojiu Fang, Fanzhi Kong, Haiqing Zhang, Bin Huang, Jifa Zhang, Xueli Zhang
Summary: Mendelian randomization (MR) analysis revealed that IL-16, IL-18, and CXCL10 are positively associated with inflammatory bowel disease (IBD), while IL-12p70 and CCL23 are negatively associated with IBD. IL-16 and IL-18 may increase the risk of ulcerative colitis (UC), and CXCL10 may increase the risk of Crohn's disease (CD). However, there is no evidence to support a causal relationship between IBD and its main subtypes (UC and CD) with the levels of ILs and chemokines. Sensitivity analyses showed robust results without heterogeneity and pleiotropy.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Nutrition & Dietetics
Majid Nikpay, Sepehr Ravati, Robert Dent, Ruth McPherson
Summary: The study identified multiple methylation sites causally contributing to the risk of obesity through a multiomics approach, and validated these findings through replication. The results showed that changes in methylation levels can affect obesity by regulating gene expression. Additionally, rare variants within 2p23.3 region impact obesity risk by influencing the susceptibility of methylation sites and subsequently altering gene expression levels.
Article
Endocrinology & Metabolism
Xichang Wang, Xiaotong Gao, Yutong Han, Fan Zhang, Zheyu Lin, Hong Wang, Weiping Teng, Zhongyan Shan
Summary: Genetically driven serum TSH level was not found to causally lead to changes in BMI or obesity according to IVW and MR-Egger results. However, genetically predicted high BMI was shown to significantly elevate TSH levels, and BMI was found to causally increase fT3 levels.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Medicine, General & Internal
Jaeyoon Chung, Viha Vig, Xinyu Sun, Xudong Han, George T. O'Connor, Xuejing Chen, Margaret M. DeAngelis, Lindsay A. Farrer, Manju L. Subramanian
Summary: Age-related macular degeneration (AMD) is a risk factor for severe consequences from COVID-19. Genetic analysis shows a significant correlation between AMD and COVID-19, and identified novel genetic associations between the two diseases.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Endocrinology & Metabolism
Alice Giontella, Loukas Zagkos, Milan Geybels, Susanna C. Larsson, Ioanna Tzoulaki, Christos S. Mantzoros, Birgitte Andersen, Dipender Gill, Helene T. Cronje
Summary: This study investigates the effects of fibroblast growth factor 21 (FGF21) on kidney function using a genetic variant as an instrumental variable. The results suggest that genetically predicted FGF21 has renoprotective effects and is associated with lower risk of chronic kidney disease (CKD) and improved cardiometabolic profiles. This highlights the potential repurposing opportunity of FGF21 for the treatment and prevention of kidney disease.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2023)
Article
Oncology
Jeroen J. van den Broek, Clyde B. Schechter, Nicolien T. van Ravesteyn, A. Cecile J. W. Janssens, Michael C. Wolfson, Amy Trentham-Dietz, Jacques Simard, Douglas F. Easton, Jeanne S. Mandelblatt, Peter Kraft, Harry J. de Koning
Summary: Breast cancer family history and polygenic risk score can guide screening decisions for women aged 30-50 years. Combining family history and PRS has greater benefits in terms of life-years gained and breast cancer deaths averted compared to biennial screening from 50 to 74 years old.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2021)
Article
Oncology
Anna Plym, Kathryn L. Penney, Sarah Kalia, Peter Kraft, David Conti, Christopher Haiman, Lorelei A. Mucci, Adam S. Kibel
Summary: The study evaluated a multiethnic polygenic risk score model for prostate cancer and found that it was strongly associated with prostate cancer risk and could be used to identify individuals at high risk.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2022)
Article
Oncology
Nicholas J. Boddicker, Chunling Hu, Jeffrey N. Weitzel, Peter Kraft, Katherine L. Nathanson, David E. Goldgar, Jie Na, Hongyan Huang, Rohan D. Gnanaolivu, Nicole Larson, Amal Yussuf, Song Yao, Celine M. Vachon, Amy Trentham-Dietz, Lauren Teras, Jack A. Taylor, Christopher E. Scott, Dale P. Sandler, Tina Pesaran, Alpa Patel, Julie R. Palmer, Irene M. Ong, Janet E. Olson, Katie O'Brien, Susan Neuhausen, Elena Martinez, Huiyan Ma, Sara Lindstrom, Loic Le Marchand, Charles Kooperberg, Rachid Karam, David J. Hunter, James M. Hodge, Christopher Haiman, Mia M. Gaudet, Chi Gao, Holly LaDuca, James Lacey, Jill S. Dolinsky, Elizabeth Chao, Brian D. Carter, Elizabeth S. Burnside, Kimberly A. Bertrand, Leslie Bernstein, Paul W. Auer, Christine Ambrosone, Siddhartha Yadav, Steven N. Hart, Eric C. Polley, Susan M. Domchek, Fergus J. Couch
Summary: This study identified the prevalence of germline pathogenic variants (PVs) in established breast cancer predisposition genes in women over age 65 years. It found that women with PVs in BRCA1, BRCA2, and PALB2 have an increased risk of breast cancer. The study suggests that genetic testing should be considered for women diagnosed with triple-negative or ER-negative breast cancer, and MRI screening may be beneficial for women over age 65 with certain PVs.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Oncology
Siddhartha Yadav, Chunling Hu, Katherine L. Nathanson, Jeffrey N. Weitzel, David E. Goldgar, Peter Kraft, Rohan D. Gnanaolivu, Jie Na, Hongyan Huang, Nicholas J. Boddicker, Nicole Larson, Chi Gao, Song Yao, Clarice Weinberg, Celine M. Vachon, Amy Trentham-Dietz, Jack A. Taylor, Dale R. Sandler, Alpa Patel, Julie R. Palmer, Janet E. Olson, Susan Neuhausen, Elena Martinez, Sara Lindstrom, James V. Lacey, Allison W. Kurian, Esther M. John, Christopher Haiman, Leslie Bernstein, Paul W. Auer, Hoda Anton-Culver, Christine B. Ambrosone, Rachid Karam, Elizabeth Chao, Amal Yussuf, Tina Pesaran, Jill S. Dolinsky, Steven N. Hart, Holly LaDuca, Eric C. Polley, Susan M. Domchek, Fergus J. Couch
Summary: The study found that ATM, BRCA2, CDH1, CHEK2, and PALB2 pathogenic variants are associated with an increased risk of ILC, while BRCA1 pathogenic variants are not. CDH1 pathogenic variants are significantly enriched in ILC, while BRCA1 pathogenic variants are substantially reduced.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Genetics & Heredity
Yuxi Liu, Alexander Gusev, Yujing J. Heng, Ludmil B. Alexandrov, Peter Kraft
Summary: Our analysis reveals robust associations between tumor somatic mutational profiles and germline polygenic risk scores, indicating the potential roles of hormone regulation and immune responses in cancer etiology and progression.
Article
Obstetrics & Gynecology
Renee M. G. Verdiesen, Yvonne T. van der Schouw, Carla H. van Gils, W. M. Monique Verschuren, Frank J. M. Broekmans, Maria C. Borges, Ana L. Goncalves Soares, Deborah A. Lawlor, A. Heather Eliassen, Peter Kraft, Dale P. Sandler, Sioban D. Harlow, Jennifer A. Smith, Nanette Santoro, Minouk J. Schoemaker, Anthony J. Swerdlow, Anna Murray, Katherine S. Ruth, N. Charlotte Onland-Moret
Summary: This study identified four loci associated with circulating anti-Müllerian hormone levels in premenopausal women through a large-scale genome-wide association study meta-analysis. The findings contribute to the understanding of the biology of anti-Müllerian hormone and its role in ovarian aging.
HUMAN REPRODUCTION
(2022)
Article
Biochemistry & Molecular Biology
Limin Hao, Peter Kraft, Gabriel F. Berriz, Elizabeth D. Hynes, Christopher Koch, Prathik Kumar, Shruti S. Parpattedar, Marcie Steeves, Wanfeng Yu, Ashley A. Antwi, Charles A. Brunette, Morgan Danowski, Manish K. Gala, Robert C. Green, Natalie E. Jones, Anna C. F. Lewis, Steven A. Lubitz, Pradeep Natarajan, Jason L. Vassy, Matthew S. Lebo
Summary: The first report from the GenoVA Study provides insights into the development of a clinical polygenic risk score assay and discusses the challenges of implementing and reporting the results. The study developed a clinical genotype array-based assay for multiple conditions and analyzed prospective samples to determine the frequency of high-risk polygenic risk scores. The research highlights the importance of developing resources and workflows for using polygenic risk score information in patient care.
Article
Medicine, General & Internal
Jordi Merino, Marta Guasch-Ferre, Jun Li, Wonil Chung, Yang Hu, Baoshan Ma, Yanping Li, Jae H. Kang, Peter Kraft, Liming Liang, Qi Sun, Paul W. Franks, JoAnn E. Manson, Walter C. Willet, Jose C. Florez, Frank B. Hu
Summary: This study identifies the independent associations of genetic risk and diet quality with incident type 2 diabetes, suggesting that a healthy diet is associated with lower diabetes risk across all levels of genetic risk.
Article
Endocrinology & Metabolism
Qianwen Liu, Bowen Tang, Zhaozhong Zhu, Peter Kraft, Qiaolin Deng, Elisabet Stener-Victorin, Xia Jiang
Summary: The genetic link between type 2 diabetes, glycaemic traits and PCOS was found, influenced by both biological pleiotropy and causal mediation, some of which is independent of BMI. The study highlights the importance of controlling fasting insulin levels to mitigate the risk of PCOS, as well as screening for and monitoring type 2 diabetes in all women with PCOS, irrespective of BMI.
Article
Oncology
Anna Plym, Yiwen Zhang, Konrad H. Stopsack, Yon Ho Jee, Fredrik Wiklund, Adam S. Kibel, Peter Kraft, Edward Giovannucci, Kathryn L. Penney, Lorelei A. Mucci
Summary: Family history and inherited polygenic risk assessment can help identify men at higher risk of developing and dying from prostate cancer.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Joy Shi, Peter Kraft, Bernard A. Rosner, Yolanda Benavente, Amanda Black, Louise A. Brinton, Chu Chen, Megan A. Clarke, Linda S. Cook, Laura Costas, Luigino Dal Maso, Jo L. Freudenheim, Jon Frias-Gomez, Christine M. Friedenreich, Montserrat Garcia-Closas, Marc T. Goodman, Lisa Johnson, Carlo La Vecchia, Fabio Levi, Jolanta Lissowska, Lingeng Lu, Susan E. McCann, Kirsten B. Moysich, Eva Negri, Kelli O'Connell, Fabio Parazzini, Stacey Petruzella, Jerry Polesel, Jeanette Ponte, Timothy R. Rebbeck, Peggy Reynolds, Fulvio Ricceri, Harvey A. Risch, Carlotta Sacerdote, Veronica W. Setiawan, Xiao-Ou Shu, Amanda B. Spurdle, Britton Trabert, Penelope M. Webb, Nicolas Wentzensen, Lynne R. Wilkens, Wang Hong Xu, Hannah P. Yang, Herbert Yu, Mengmeng Du, Immaculata De Vivo
Summary: To mitigate the burden of endometrial cancer, risk stratification can help target interventions. The study developed risk prediction models using data from postmenopausal White women aged 45-85 years. The models based on epidemiologic factors alone successfully identified women at high risk of endometrial cancer, with limited improvements from genetic factors.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2023)
Article
Oncology
Jihye Kim, Chen Yuan, Laufey T. Amundadottir, Brian M. Wolpin, Alison P. Klein, Harvey A. Risch, Peter Kraft
Summary: Non-O blood types have a greater risk of pancreatic ductal adenocarcinoma (PDAC) among Western populations. This risk is stronger among secretors than non-secretors, but not influenced by Lewis antigens.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2023)
Article
Oncology
Yuxi Liu, Alexander Gusev, Peter Kraft
Summary: Somatic mutations in cancer can be influenced by the genetic background of germline variants, which may affect the expression of specific cancer genes. By integrating tumor sequencing data with germline cancer gene expression data, it was found that variants upregulating ATM expression were associated with a decreased risk of somatic ATM mutations in multiple cancer types. Additionally, eQTLs related to gene expression of GLI2, WRN, CBFB, EPHA5, APC, GLI1, FANCA, and TP53 were associated with mutations in specific cancer genes in different cancer types. These findings suggest that germline-somatic associations are mediated through the expression of specific cancer genes, providing new insights for further research.
Article
Oncology
Sara Lindstrom, Lu Wang, Helian Feng, Arunabha Majumdar, Sijia Huo, James Macdonald, Tabitha Harrison, Constance Turman, Hongjie Chen, Nicholas Mancuso, Theo Bammler, Steve Gallinger, Stephen B. Gruber, Marc J. Gunter, Loic Le Marchand, Victor Moreno, Kenneth Offit, Immaculata De Vivo, Tracy A. O'Mara, Amanda B. Spurdle, Ian Tomlinson, Rebecca Fitzgerald, Puya Gharahkhani, Ines Gockel, Janusz Jankowski, Stuart Macgregor, Johannes Schumacher, Jill Barnholtz-Sloan, Melissa L. Bondy, Richard S. Houlston, Robert B. Jenkins, Beatrice Melin, Margaret Wrensch, Paul Brennan, David C. Christiani, Mattias Johansson, James Mckay, Melinda C. Aldrich, Christopher Amos, Maria Teresa Landi, Adonina Tardon, D. Timothy Bishop, Florence Demenais, Alisa M. Goldstein, Mark M. Iles, Peter A. Kanetsky, Matthew H. Law, Laufey T. Amundadottir, Rachael Stolzenberg-Solomon, Brian M. Wolpin, Alison Klein, Gloria Petersen, Harvey Risch, Stephen J. Chanock, Mark P. Purdue, Ghislaine Scelo, Paul Pharoah, Siddhartha Kar, Rayjean J. Hung, Bogdan Pasaniuc, Peter Kraft
Summary: This study quantified the shared genetic contribution to risk of different cancers and identified novel cancer susceptibility loci using data from 12 cancer genome-wide association studies. The results suggest that some genetic risk variants are shared among cancers, but most of cancer heritability is specific to certain tissues. Cross-disease analysis allows for increased statistical power and the identification of new susceptibility regions. Future studies are likely to discover additional regions associated with the risk of multiple cancer types.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2023)
Article
Oncology
Chaoran Ma, Xiaoyu Wang, James Y. Dai, Constance Turman, Peter Kraft, Konrad H. Stopsack, Massimo Loda, Andreas Pettersson, Lorelei A. Mucci, Janet L. Stanford, Kathryn L. Penney
Summary: This study investigated the germline genetic variants associated with TMPRSS2:ERG fusion status in prostate cancer cases. The findings suggest that tumors with TMPRSS2:ERG fusion have a different genetic etiology compared to fusion negative cases. The study identified several SNPs at known prostate cancer risk loci that were differentially associated with the risk of developing prostate tumors with or without the gene fusion.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2023)