Guo, Xiuqing
Mayo Clinic
The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center Torrance CA USA.
Citations 2
Association Between Whole Blood–Derived Mitochondrial DNA Copy Number, Low‐Density Lipoprotein Cholesterol, and Cardiovascular Disease Risk
Liu, Xue , Sun, Xianbang, Jiang, Wenqing , Lai, M M , Wiggins, Kerri L. , Raffield, Laura M. , Bielak, Lawrence F. , Zhao, Wei , Pitsillides, Achilleas , Haessler, Jeffrey, Blackwell, Thomas W. , Yao, Jie , Qian, Yong , Thyagarajan, Bharat , Peyser, Patricia A. , Heckbert, Susan R. , Seshadri, Sudha , Boerwinkle, Eric , Grove, Megan L. , Larson, Nicholas B. , Smith, Jennifer A. , Fitzpatrick, Annette L., Fornage, Myriam , Ding, Jun , Carson, April P. , Reiner, Alex P. , Hou, Lifang , Wilson, James G. , Rotter, Jerome I. , Bis, Joshua C. , Arking, Dan E. , Zhao, Wei , Wiggins, Kerri L , Raffield, Laura M , Bielak, Lawrence F , Zhao, Wei , Pitsillides, Achilleas , Zheng, Yinan , Yao, Jie , Guo, Xiuqing , Thyagarajan, Bharat , Pankratz, Nathan , Rich, Stephen S , Taylor, Kent D , Peyser, Patricia A , Heckbert, Susan R , Boerwinkle, Eric , Larson, Nicholas B , Smith, Jennifer A , Vasan, Ramachandran S , Fornage, Myriam , Carson, April P , Dupuis, Josée , Reiner, Alexander P , Hou, Lifang , Psaty, Bruce M , Levy, Daniel , Rotter, Jerome I , Bis, Joshua C , Satizabal, Claudia L , Arking, Dan E , Liu, Chunyu , Seshadri, Sudha , Zhang, Yuankai , Zheng, Yinan , Guo, Xiuqing , Pankratz, Nathan , Rich, Stephen S. , Taylor, Kent D. , Vasan, Ramachandran S. , Abecasis, Gonçalo R. , Kooperberg, Charles , Psaty, Bruce M. , Levy, Daniel , Satizábal, Claudia L.
Journal of the American Heart Association | October 7, 2023 | Volume: 12 | Issue: 20 | Pages: No page available
Background The relationship between mitochondrial DNA copy number (mtDNA CN) and cardiovascular disease remains elusive. Methods and Results We performed cross‐sectional and prospective association analyses of blood‐derived mtDNA CN and cardiovascular disease outcomes in 27 316 participants in 8 cohorts of multiple racial and ethnic groups with whole‐genome sequencing. We also performed Mendelian randomization to explore causal relationships of mtDNA CN with coronary heart disease (CHD) and cardiometabolic risk factors (obesity, diabetes, hypertension, and hyperlipidemia). P <0.01 was used for significance. We validated most of the previously reported associations between mtDNA CN and cardiovascular disease outcomes. For example, 1‐SD unit lower level of mtDNA CN was associated with 1.08 (95% CI, 1.04–1.12; P <0.001) times the hazard for developing incident CHD, adjusting for covariates. Mendelian randomization analyses showed no causal effect from a lower level of mtDNA CN to a higher CHD risk (β=0.091; P =0.11) or in the reverse direction (β=−0.012; P =0.076). Additional bidirectional Mendelian randomization analyses revealed that low‐density lipoprotein cholesterol had a causal effect on mtDNA CN (β=−0.084; P <0.001), but the reverse direction was not significant ( P =0.059). No causal associations were observed between mtDNA CN and obesity, diabetes, and hypertension, in either direction. Multivariable Mendelian randomization analyses showed no causal effect of CHD on mtDNA CN, controlling for low‐density lipoprotein cholesterol level ( P =0.52), whereas there was a strong direct causal effect of higher low‐density lipoprotein cholesterol on lower mtDNA CN, adjusting for CHD status (β=−0.092; P <0.001). Conclusions Our findings indicate that high low‐density lipoprotein cholesterol may underlie the complex relationships between mtDNA CN and vascular atherosclerosis.
The genetic determinants of recurrent somatic mutations in 43,693 blood genomes
Weinstock, Joshua S. , Laurie, Cecelia , Broome, Jai , Taylor, Kent D. , Guo, Xiuqing , Shuldiner, Alan R. , O’Connell, Jeffrey R. , Lewis, Joshua P. , Boerwinkle, Eric , Barnes, Kathleen C. , Chami, Nathalie , Loos, Ruth J. F. , Fornage, Myriam , Redline, Susan , Cade, Brian E. , Chen, Zhanghua , Gauderman, W. James , Schleimer, Robert P. , Bis, Joshua C. , Brody, Jennifer A. , Silverman, Edwin K. , Qiao, Dandi , Lasky‐Su, Jessica , DeMeo, Dawn L. , Palmer, Nicholette D. , Bowden, Donald W. , Johnson, Andrew D. , Yanek, Lisa R. , Becker, Lewis C. , Kardia, Sharon L.R., Kaplan, Robert C. , Heckbert, Susan R. , Smith, Nicholas L. , Arnett, Donna K. , Irvin, Marguerite R. , Tiwari, Hemant K., Raffield, Laura M. , Gao, Yan , Rotter, Jerome I. , Wheeler, Marsha M. , Duggirala, Ravindranath , Xiao, Shujie, Williams, L. Keoki , Meyers, Deborah A. , Ortega, Victor E. , McGarvey, Stephen T. , Chen, Yii‐Der Ida , Lee, Wen‐Jane , Shoemaker, M. Benjamin , Roden, Dan M. , Blackwell, Thomas W. , Smith, Albert V. , Kang, Hyun Min , Mathias, Rasika A. , Natarajan, Pradeep , Jaiswal, Siddhartha , Reiner, Alex P. , Bick, Alexander G. , Kaplan, Robert C. , Broome, Jai , Kenny, Eimear E , Loos, Ruth J F , Fornage, Myriam , Redline, Susan , Cade, Brian E , Gauderman, W James , Grammer, Leslie , Schleimer, Robert P , Bis, Joshua C , Brody, Jennifer A , Silverman, Edwin K , Yun, Jeong H , Qiao, Dandi , Weiss, Scott T , Palmer, Nicholette D , Freedman, Barry I , Cho, Michael H , Vasan, Ramachandran S , Johnson, Andrew D , Yanek, Lisa R , Becker, Lewis C , He, Jiang , Heckbert, Susan R , Wiggins, Kerri L , Arnett, Donna K , Correa, Adolfo , Raffield, Laura M , Gao, Yan , Rotter, Jerome I , Rich, Stephen S , Manichaikul, Ani W , Konkle, Barbara A , Johnsen, Jill M , Custer, Brian S , Duggirala, Ravindranath , Curran, Joanne E , Li, Xingnan , McGarvey, Stephen T , Gu, C Charles , Lee, Wen-Jane , Darbar, Dawood , Roden, Dan M. , Kooperberg, Charles , Desai, Pinkal M , Smith, Albert V , Kang, Hyun M , Mathias, Rasika A , Natarajan, Pradeep , Jaiswal, Siddhartha , Bick, Alexander G , Weinstock, Joshua S , Shuldiner, Alan R , Taylor, Kent D , Guo, Xiuqing , Lasky-Su, Jessica , Gilliland, Frank D. , Kumar, Rajesh , Psaty, Bruce M. , Yun, Jeong H. , Weiss, Scott T. , Freedman, Barry I. , Cho, Michael H. , Vasan, Ramachandran S. , He, Jiang , Wiggins, Kerri L. , Andrade, Mariza de , Rich, Stephen S. , Manichaikul, Ani , Konkle, Barbara A. , Custer, Brian , Curran, Joanne E. , Blangero, John , Gui, Hongsheng , Li, Xingnan , Darbar, Dawood , Albert, Christine M. , Kooperberg, Charles , Desai, Pinkal , Abecasis, Gonçalo R.
Science Advances | April 26, 2023 | Volume: 9 | Issue: 17 | Pages: No page available
Nononcogenic somatic mutations are thought to be uncommon and inconsequential. To test this, we analyzed 43,693 National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine blood whole genomes from 37 cohorts and identified 7131 non-missense somatic mutations that are recurrently mutated in at least 50 individuals. These recurrent non-missense somatic mutations (RNMSMs) are not clearly explained by other clonal phenomena such as clonal hematopoiesis. RNMSM prevalence increased with age, with an average 50-year-old having 27 RNMSMs. Inherited germline variation associated with RNMSM acquisition. These variants were found in genes involved in adaptive immune function, proinflammatory cytokine production, and lymphoid lineage commitment. In addition, the presence of eight specific RNMSMs associated with blood cell traits at effect sizes comparable to Mendelian genetic mutations. Overall, we found that somatic mutations in blood are an unexpectedly common phenomenon with ancestry-specific determinants and human health consequences.