Author: "He, Jiang" / Publication Type: Electronic Resources - Searchworks@Jio Institute Digital Library Search Results

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247 results on '"He, Jiang"'

1. Development of CD46 targeted alpha theranostics in prostate cancer using 134Ce/225Ac-Macropa-PEG4-YS5

Author: Bobba, Kondapa Naidu, Bobba, Kondapa Naidu, Bidkar, Anil P, Wadhwa, Anju, Meher, Niranjan, Drona, Suchi, Sorlin, Alexandre M, Bidlingmaier, Scott, Zhang, Li, Wilson, David M, Chan, Emily, Greenland, Nancy Y, Aggarwal, Rahul, VanBrocklin, Henry F, He, Jiang, Chou, Jonathan, Seo, Youngho, Liu, Bin, Flavell, Robert R, Bobba, Kondapa Naidu, Bobba, Kondapa Naidu, Bidkar, Anil P, Wadhwa, Anju, Meher, Niranjan, Drona, Suchi, Sorlin, Alexandre M, Bidlingmaier, Scott, Zhang, Li, Wilson, David M, Chan, Emily, Greenland, Nancy Y, Aggarwal, Rahul, VanBrocklin, Henry F, He, Jiang, Chou, Jonathan, Seo, Youngho, Liu, Bin, and Flavell, Robert R
Published: 2024

2. Validation of human telomere length multi-ancestry meta-analysis association signals identifies POP5 and KBTBD6 as human telomere length regulation genes

Author: Keener, Rebecca, Keener, Rebecca, Chhetri, Surya B, Connelly, Carla J, Taub, Margaret A, Conomos, Matthew P, Weinstock, Joshua, Ni, Bohan, Strober, Benjamin, Aslibekyan, Stella, Auer, Paul L, Barwick, Lucas, Becker, Lewis C, Blangero, John, Bleecker, Eugene R, Brody, Jennifer A, Cade, Brian E, Celedon, Juan C, Chang, Yi-Cheng, Cupples, L Adrienne, Custer, Brian, Freedman, Barry I, Gladwin, Mark T, Heckbert, Susan R, Hou, Lifang, Irvin, Marguerite R, Isasi, Carmen R, Johnsen, Jill M, Kenny, Eimear E, Kooperberg, Charles, Minster, Ryan L, Naseri, Take, Viali, Satupa’itea, Nekhai, Sergei, Pankratz, Nathan, Peyser, Patricia A, Taylor, Kent D, Telen, Marilyn J, Wu, Baojun, Yanek, Lisa R, Yang, Ivana V, Albert, Christine, Arnett, Donna K, Ashley-Koch, Allison E, Barnes, Kathleen C, Bis, Joshua C, Blackwell, Thomas W, Boerwinkle, Eric, Burchard, Esteban G, Carson, April P, Chen, Zhanghua, Chen, Yii-Der Ida, Darbar, Dawood, de Andrade, Mariza, Ellinor, Patrick T, Fornage, Myriam, Gelb, Bruce D, Gilliland, Frank D, He, Jiang, Islam, Talat, Kaab, Stefan, Kardia, Sharon LR, Kelly, Shannon, Konkle, Barbara A, Kumar, Rajesh, Loos, Ruth JF, Martinez, Fernando D, McGarvey, Stephen T, Meyers, Deborah A, Mitchell, Braxton D, Montgomery, Courtney G, North, Kari E, Palmer, Nicholette D, Peralta, Juan M, Raby, Benjamin A, Redline, Susan, Rich, Stephen S, Roden, Dan, Rotter, Jerome I, Ruczinski, Ingo, Schwartz, David, Sciurba, Frank, Shoemaker, M Benjamin, Silverman, Edwin K, Sinner, Moritz F, Smith, Nicholas L, Smith, Albert V, Tiwari, Hemant K, Vasan, Ramachandran S, Weiss, Scott T, Williams, L Keoki, Zhang, Yingze, Ziv, Elad, Raffield, Laura M, Reiner, Alexander P, Arvanitis, Marios, Greider, Carol W, Mathias, Rasika A, Battle, Alexis, Keener, Rebecca, Keener, Rebecca, Chhetri, Surya B, Connelly, Carla J, Taub, Margaret A, Conomos, Matthew P, Weinstock, Joshua, Ni, Bohan, Strober, Benjamin, Aslibekyan, Stella, Auer, Paul L, Barwick, Lucas, Becker, Lewis C, Blangero, John, Bleecker, Eugene R, Brody, Jennifer A, Cade, Brian E, Celedon, Juan C, Chang, Yi-Cheng, Cupples, L Adrienne, Custer, Brian, Freedman, Barry I, Gladwin, Mark T, Heckbert, Susan R, Hou, Lifang, Irvin, Marguerite R, Isasi, Carmen R, Johnsen, Jill M, Kenny, Eimear E, Kooperberg, Charles, Minster, Ryan L, Naseri, Take, Viali, Satupa’itea, Nekhai, Sergei, Pankratz, Nathan, Peyser, Patricia A, Taylor, Kent D, Telen, Marilyn J, Wu, Baojun, Yanek, Lisa R, Yang, Ivana V, Albert, Christine, Arnett, Donna K, Ashley-Koch, Allison E, Barnes, Kathleen C, Bis, Joshua C, Blackwell, Thomas W, Boerwinkle, Eric, Burchard, Esteban G, Carson, April P, Chen, Zhanghua, Chen, Yii-Der Ida, Darbar, Dawood, de Andrade, Mariza, Ellinor, Patrick T, Fornage, Myriam, Gelb, Bruce D, Gilliland, Frank D, He, Jiang, Islam, Talat, Kaab, Stefan, Kardia, Sharon LR, Kelly, Shannon, Konkle, Barbara A, Kumar, Rajesh, Loos, Ruth JF, Martinez, Fernando D, McGarvey, Stephen T, Meyers, Deborah A, Mitchell, Braxton D, Montgomery, Courtney G, North, Kari E, Palmer, Nicholette D, Peralta, Juan M, Raby, Benjamin A, Redline, Susan, Rich, Stephen S, Roden, Dan, Rotter, Jerome I, Ruczinski, Ingo, Schwartz, David, Sciurba, Frank, Shoemaker, M Benjamin, Silverman, Edwin K, Sinner, Moritz F, Smith, Nicholas L, Smith, Albert V, Tiwari, Hemant K, Vasan, Ramachandran S, Weiss, Scott T, Williams, L Keoki, Zhang, Yingze, Ziv, Elad, Raffield, Laura M, Reiner, Alexander P, Arvanitis, Marios, Greider, Carol W, Mathias, Rasika A, and Battle, Alexis
Abstract: Genome-wide association studies (GWAS) have become well-powered to detect loci associated with telomere length. However, no prior work has validated genes nominated by GWAS to examine their role in telomere length regulation. We conducted a multi-ancestry meta-analysis of 211,369 individuals and identified five novel association signals. Enrichment analyses of chromatin state and cell-type heritability suggested that blood/immune cells are the most relevant cell type to examine telomere length association signals. We validated specific GWAS associations by overexpressing KBTBD6 or POP5 and demonstrated that both lengthened telomeres. CRISPR/Cas9 deletion of the predicted causal regions in K562 blood cells reduced expression of these genes, demonstrating that these loci are related to transcriptional regulation of KBTBD6 and POP5. Our results demonstrate the utility of telomere length GWAS in the identification of telomere length regulation mechanisms and validate KBTBD6 and POP5 as genes affecting telomere length regulation.
Published: 2024

3. Glycolytic lactate in diabetic kidney disease.

Author: Darshi, Manjula, Darshi, Manjula, Kugathasan, Luxcia, Maity, Soumya, Sridhar, Vikas, Fernandez, Roman, Limonte, Christine, Grajeda, Brian, Saliba, Afaf, Zhang, Guanshi, Drel, Viktor, Kim, Jiwan, Montellano, Richard, Tumova, Jana, Montemayor, Daniel, Wang, Zhu, Liu, Jian-Jun, Wang, Jiexun, Perkins, Bruce, Lytvyn, Yuliya, Natarajan, Loki, Lim, Su, Feldman, Harold, Toto, Robert, Sedor, John, Patel, Jiten, Waikar, Sushrut, Brown, Julia, Osman, Yahya, He, Jiang, Chen, Jing, Reeves, W, de Boer, Ian, Roy, Sourav, Vallon, Volker, Hallan, Stein, Gelfond, Jonathan, Cherney, David, Sharma, Kumar, Darshi, Manjula, Darshi, Manjula, Kugathasan, Luxcia, Maity, Soumya, Sridhar, Vikas, Fernandez, Roman, Limonte, Christine, Grajeda, Brian, Saliba, Afaf, Zhang, Guanshi, Drel, Viktor, Kim, Jiwan, Montellano, Richard, Tumova, Jana, Montemayor, Daniel, Wang, Zhu, Liu, Jian-Jun, Wang, Jiexun, Perkins, Bruce, Lytvyn, Yuliya, Natarajan, Loki, Lim, Su, Feldman, Harold, Toto, Robert, Sedor, John, Patel, Jiten, Waikar, Sushrut, Brown, Julia, Osman, Yahya, He, Jiang, Chen, Jing, Reeves, W, de Boer, Ian, Roy, Sourav, Vallon, Volker, Hallan, Stein, Gelfond, Jonathan, Cherney, David, and Sharma, Kumar
Abstract: Lactate elevation is a well-characterized biomarker of mitochondrial dysfunction, but its role in diabetic kidney disease (DKD) is not well defined. Urine lactate was measured in patients with type 2 diabetes (T2D) in 3 cohorts (HUNT3, SMART2D, CRIC). Urine and plasma lactate were measured during euglycemic and hyperglycemic clamps in participants with type 1 diabetes (T1D). Patients in the HUNT3 cohort with DKD had elevated urine lactate levels compared with age- and sex-matched controls. In patients in the SMART2D and CRIC cohorts, the third tertile of urine lactate/creatinine was associated with more rapid estimated glomerular filtration rate decline, relative to first tertile. Patients with T1D demonstrated a strong association between glucose and lactate in both plasma and urine. Glucose-stimulated lactate likely derives in part from proximal tubular cells, since lactate production was attenuated with sodium-glucose cotransporter-2 (SGLT2) inhibition in kidney sections and in SGLT2-deficient mice. Several glycolytic genes were elevated in human diabetic proximal tubules. Lactate levels above 2.5 mM potently inhibited mitochondrial oxidative phosphorylation in human proximal tubule (HK2) cells. We conclude that increased lactate production under diabetic conditions can contribute to mitochondrial dysfunction and become a feed-forward component to DKD pathogenesis.
Published: 2024

4. Treatment of prostate cancer with CD46 targeted 225Ac alpha particle radioimmunotherapy

Author: Bidkar, Anil P, Bidkar, Anil P, Wang, Sinan, Bobba, Kondapa Naidu, Chan, Emily, Bidlingmaier, Scott, Egusa, Emily A, Peter, Robin, Ali, Umama, Meher, Niranjan, Wadhwa, Anju, Dhrona, Suchi, Dasari, Chandrashekhar, Beckford-Vera, Denis, Su, Yang, Tang, Ryan, Zhang, Li, He, Jiang, Wilson, David M, Aggarwal, Rahul, VanBrocklin, Henry F, Seo, Youngho, Chou, Jonathan, Liu, Bin, Flavell, Robert R, Bidkar, Anil P, Bidkar, Anil P, Wang, Sinan, Bobba, Kondapa Naidu, Chan, Emily, Bidlingmaier, Scott, Egusa, Emily A, Peter, Robin, Ali, Umama, Meher, Niranjan, Wadhwa, Anju, Dhrona, Suchi, Dasari, Chandrashekhar, Beckford-Vera, Denis, Su, Yang, Tang, Ryan, Zhang, Li, He, Jiang, Wilson, David M, Aggarwal, Rahul, VanBrocklin, Henry F, Seo, Youngho, Chou, Jonathan, Liu, Bin, and Flavell, Robert R
Published: 2023

5. Ultraprocessed Foods and Kidney Disease Progression, Mortality, and Cardiovascular Disease Risk in the CRIC Study.

Author: Sullivan, Valerie, Sullivan, Valerie, Appel, Lawrence, Anderson, Cheryl, Kim, Hyunju, Unruh, Mark, Lash, James, Trego, Marsha, Sondheimer, James, Dobre, Mirela, Pradhan, Nishigandha, Rao, Panduranga, Chen, Jing, He, Jiang, Rebholz, Casey, Sullivan, Valerie, Sullivan, Valerie, Appel, Lawrence, Anderson, Cheryl, Kim, Hyunju, Unruh, Mark, Lash, James, Trego, Marsha, Sondheimer, James, Dobre, Mirela, Pradhan, Nishigandha, Rao, Panduranga, Chen, Jing, He, Jiang, and Rebholz, Casey
Abstract: RATIONALE & OBJECTIVE: Ultraprocessed foods are widely consumed in the United States and are associated with cardiovascular disease (CVD), mortality, and kidney function decline in the general population. We investigated associations between ultraprocessed food intake and chronic kidney disease (CKD) progression, all-cause mortality, and incident CVD in adults with chronic kidney disease (CKD). STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Chronic Renal Insufficiency Cohort Study participants who completed baseline dietary questionnaires. EXPOSURE: Ultraprocessed food intake (in servings per day) classified according to the NOVA system. OUTCOMES: CKD progression (≥50% decrease in estimated glomerular filtration rate [eGFR] or initiation of kidney replacement therapy), all-cause mortality, and incident CVD (myocardial infarction, congestive heart failure, or stroke). ANALYTICAL APPROACH: Cox proportional hazards models adjusted for demographic, lifestyle, and health covariates. RESULTS: There were 1,047 CKD progression events observed during a median follow-up of 7 years. Greater ultraprocessed food intake was associated with higher risk of CKD progression (tertile 3 vs tertile 1, HR, 1.22; 95% CI, 1.04-1.42; P=0.01 for trend). The association differed by baseline kidney function, such that greater intake was associated with higher risk among people with CKD stages 1/2 (eGFR≥60mL/min/1.73m2; tertile 3 vs tertile 1, HR, 2.61; 95% CI, 1.32-5.18) but not stages 3a-5 (eGFR<60mL/min/1.73m2; P=0.003 for interaction). There were 1,104 deaths observed during a median follow-up of 14 years. Greater ultraprocessed food intake was associated with higher risk of mortality (tertile 3 vs tertile 1, HR, 1.21; 95% CI, 1.04-1.40; P=0.004 for trend). LIMITATIONS: Self-reported diet. CONCLUSIONS: Greater ultraprocessed food intake may be associated with CKD progression in earlier stages of CKD and is associated with higher risk of all-cause mortality i
Published: 2023

6. Concordance of MERFISH spatial transcriptomics with bulk and single-cell RNA sequencing.

Author: Liu, Jonathan, Liu, Jonathan, Tran, Vanessa, Vemuri, Venkata Naga Pranathi, Byrne, Ashley, Borja, Michael, Kim, Yang Joon, Agarwal, Snigdha, Wang, Ruofan, Awayan, Kyle, Murti, Abhishek, Taychameekiatchai, Aris, Wang, Bruce, Emanuel, George, He, Jiang, Haliburton, John, Oliveira Pisco, Angela, Neff, Norma F, Liu, Jonathan, Liu, Jonathan, Tran, Vanessa, Vemuri, Venkata Naga Pranathi, Byrne, Ashley, Borja, Michael, Kim, Yang Joon, Agarwal, Snigdha, Wang, Ruofan, Awayan, Kyle, Murti, Abhishek, Taychameekiatchai, Aris, Wang, Bruce, Emanuel, George, He, Jiang, Haliburton, John, Oliveira Pisco, Angela, and Neff, Norma F
Abstract: Spatial transcriptomics extends single-cell RNA sequencing (scRNA-seq) by providing spatial context for cell type identification and analysis. Imaging-based spatial technologies such as multiplexed error-robust fluorescence in situ hybridization (MERFISH) can achieve single-cell resolution, directly mapping single-cell identities to spatial positions. MERFISH produces a different data type than scRNA-seq, and a technical comparison between the two modalities is necessary to ascertain how to best integrate them. We performed MERFISH on the mouse liver and kidney and compared the resulting bulk and single-cell RNA statistics with those from the Tabula Muris Senis cell atlas and from two Visium datasets. MERFISH quantitatively reproduced the bulk RNA-seq and scRNA-seq results with improvements in overall dropout rates and sensitivity. Finally, we found that MERFISH independently resolved distinct cell types and spatial structure in both the liver and kidney. Computational integration with the Tabula Muris Senis atlas did not enhance these results. We conclude that MERFISH provides a quantitatively comparable method for single-cell gene expression and can identify cell types without the need for computational integration with scRNA-seq atlases.
Published: 2023

7. CD46 targeted 212Pb alpha particle radioimmunotherapy for prostate cancer treatment.

Author: Li, Jun, Li, Jun, Huang, Tao, Hua, Jun, Wang, Qiong, Su, Yang, Chen, Ping, Bidlingmaier, Scott, Li, Allan, Xie, Zhongqiu, Bidkar, Anil P, Shen, Sui, Shi, Weibin, Seo, Youngho, Flavell, Robert R, Gioeli, Daniel, Dreicer, Robert, Li, Hui, Liu, Bin, He, Jiang, Li, Jun, Li, Jun, Huang, Tao, Hua, Jun, Wang, Qiong, Su, Yang, Chen, Ping, Bidlingmaier, Scott, Li, Allan, Xie, Zhongqiu, Bidkar, Anil P, Shen, Sui, Shi, Weibin, Seo, Youngho, Flavell, Robert R, Gioeli, Daniel, Dreicer, Robert, Li, Hui, Liu, Bin, and He, Jiang
Abstract: We recently identified CD46 as a novel prostate cancer cell surface antigen that shows lineage independent expression in both adenocarcinoma and small cell neuroendocrine subtypes of metastatic castration resistant prostate cancer (mCRPC), discovered an internalizing human monoclonal antibody YS5 that binds to a tumor selective CD46 epitope, and developed a microtubule inhibitor-based antibody drug conjugate that is in a multi-center phase I trial for mCRPC (NCT03575819). Here we report the development of a novel CD46-targeted alpha therapy based on YS5. We conjugated 212Pb, an in vivo generator of alpha-emitting 212Bi and 212Po, to YS5 through the chelator TCMC to create the radioimmunoconjugate, 212Pb-TCMC-YS5. We characterized 212Pb-TCMC-YS5 in vitro and established a safe dose in vivo. We next studied therapeutic efficacy of a single dose of 212Pb-TCMC-YS5 using three prostate cancer small animal models: a subcutaneous mCRPC cell line-derived xenograft (CDX) model (subcu-CDX), an orthotopically grafted mCRPC CDX model (ortho-CDX), and a prostate cancer patient-derived xenograft model (PDX). In all three models, a single dose of 0.74 MBq (20 µCi) 212Pb-TCMC-YS5 was well tolerated and caused potent and sustained inhibition of established tumors, with significant increases of survival in treated animals. A lower dose (0.37 MBq or 10 µCi 212Pb-TCMC-YS5) was also studied on the PDX model, which also showed a significant effect on tumor growth inhibition and prolongation of animal survival. These results demonstrate that 212Pb-TCMC-YS5 has an excellent therapeutic window in preclinical models including PDXs, opening a direct path for clinical translation of this novel CD46-targeted alpha radioimmunotherapy for mCRPC treatment.
Published: 2023

8. The genetic determinants of recurrent somatic mutations in 43,693 blood genomes.

Author: Weinstock, Joshua S, Weinstock, Joshua S, Laurie, Cecelia A, Broome, Jai G, Taylor, Kent D, Guo, Xiuqing, Shuldiner, Alan R, O'Connell, Jeffrey R, Lewis, Joshua P, Boerwinkle, Eric, Barnes, Kathleen C, Chami, Nathalie, Kenny, Eimear E, Loos, Ruth JF, Fornage, Myriam, Redline, Susan, Cade, Brian E, Gilliland, Frank D, Chen, Zhanghua, Gauderman, W James, Kumar, Rajesh, Grammer, Leslie, Schleimer, Robert P, Psaty, Bruce M, Bis, Joshua C, Brody, Jennifer A, Silverman, Edwin K, Yun, Jeong H, Qiao, Dandi, Weiss, Scott T, Lasky-Su, Jessica, DeMeo, Dawn L, Palmer, Nicholette D, Freedman, Barry I, Bowden, Donald W, Cho, Michael H, Vasan, Ramachandran S, Johnson, Andrew D, Yanek, Lisa R, Becker, Lewis C, Kardia, Sharon, He, Jiang, Kaplan, Robert, Heckbert, Susan R, Smith, Nicholas L, Wiggins, Kerri L, Arnett, Donna K, Irvin, Marguerite R, Tiwari, Hemant, Correa, Adolfo, Raffield, Laura M, Gao, Yan, de Andrade, Mariza, Rotter, Jerome I, Rich, Stephen S, Manichaikul, Ani W, Konkle, Barbara A, Johnsen, Jill M, Wheeler, Marsha M, Custer, Brian S, Duggirala, Ravindranath, Curran, Joanne E, Blangero, John, Gui, Hongsheng, Xiao, Shujie, Williams, L Keoki, Meyers, Deborah A, Li, Xingnan, Ortega, Victor, McGarvey, Stephen, Gu, C Charles, Chen, Yii-Der Ida, Lee, Wen-Jane, Shoemaker, M Benjamin, Darbar, Dawood, Roden, Dan, Albert, Christine, Kooperberg, Charles, Desai, Pinkal, Blackwell, Thomas W, Abecasis, Goncalo R, Smith, Albert V, Kang, Hyun M, Mathias, Rasika, Natarajan, Pradeep, Jaiswal, Siddhartha, Reiner, Alexander P, Bick, Alexander G, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Weinstock, Joshua S, Weinstock, Joshua S, Laurie, Cecelia A, Broome, Jai G, Taylor, Kent D, Guo, Xiuqing, Shuldiner, Alan R, O'Connell, Jeffrey R, Lewis, Joshua P, Boerwinkle, Eric, Barnes, Kathleen C, Chami, Nathalie, Kenny, Eimear E, Loos, Ruth JF, Fornage, Myriam, Redline, Susan, Cade, Brian E, Gilliland, Frank D, Chen, Zhanghua, Gauderman, W James, Kumar, Rajesh, Grammer, Leslie, Schleimer, Robert P, Psaty, Bruce M, Bis, Joshua C, Brody, Jennifer A, Silverman, Edwin K, Yun, Jeong H, Qiao, Dandi, Weiss, Scott T, Lasky-Su, Jessica, DeMeo, Dawn L, Palmer, Nicholette D, Freedman, Barry I, Bowden, Donald W, Cho, Michael H, Vasan, Ramachandran S, Johnson, Andrew D, Yanek, Lisa R, Becker, Lewis C, Kardia, Sharon, He, Jiang, Kaplan, Robert, Heckbert, Susan R, Smith, Nicholas L, Wiggins, Kerri L, Arnett, Donna K, Irvin, Marguerite R, Tiwari, Hemant, Correa, Adolfo, Raffield, Laura M, Gao, Yan, de Andrade, Mariza, Rotter, Jerome I, Rich, Stephen S, Manichaikul, Ani W, Konkle, Barbara A, Johnsen, Jill M, Wheeler, Marsha M, Custer, Brian S, Duggirala, Ravindranath, Curran, Joanne E, Blangero, John, Gui, Hongsheng, Xiao, Shujie, Williams, L Keoki, Meyers, Deborah A, Li, Xingnan, Ortega, Victor, McGarvey, Stephen, Gu, C Charles, Chen, Yii-Der Ida, Lee, Wen-Jane, Shoemaker, M Benjamin, Darbar, Dawood, Roden, Dan, Albert, Christine, Kooperberg, Charles, Desai, Pinkal, Blackwell, Thomas W, Abecasis, Goncalo R, Smith, Albert V, Kang, Hyun M, Mathias, Rasika, Natarajan, Pradeep, Jaiswal, Siddhartha, Reiner, Alexander P, Bick, Alexander G, and NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
Abstract: Nononcogenic somatic mutations are thought to be uncommon and inconsequential. To test this, we analyzed 43,693 National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine blood whole genomes from 37 cohorts and identified 7131 non-missense somatic mutations that are recurrently mutated in at least 50 individuals. These recurrent non-missense somatic mutations (RNMSMs) are not clearly explained by other clonal phenomena such as clonal hematopoiesis. RNMSM prevalence increased with age, with an average 50-year-old having 27 RNMSMs. Inherited germline variation associated with RNMSM acquisition. These variants were found in genes involved in adaptive immune function, proinflammatory cytokine production, and lymphoid lineage commitment. In addition, the presence of eight specific RNMSMs associated with blood cell traits at effect sizes comparable to Mendelian genetic mutations. Overall, we found that somatic mutations in blood are an unexpectedly common phenomenon with ancestry-specific determinants and human health consequences.
Published: 2023

9. Multi-ancestry transcriptome-wide association analyses yield insights into tobacco use biology and drug repurposing.

Author: Chen, Fang, Chen, Fang, Wang, Xingyan, Jang, Seon-Kyeong, Quach, Bryan C, Weissenkampen, J Dylan, Khunsriraksakul, Chachrit, Yang, Lina, Sauteraud, Renan, Albert, Christine M, Allred, Nicholette DD, Arnett, Donna K, Ashley-Koch, Allison E, Barnes, Kathleen C, Barr, R Graham, Becker, Diane M, Bielak, Lawrence F, Bis, Joshua C, Blangero, John, Boorgula, Meher Preethi, Chasman, Daniel I, Chavan, Sameer, Chen, Yii-Der I, Chuang, Lee-Ming, Correa, Adolfo, Curran, Joanne E, David, Sean P, Fuentes, Lisa de Las, Deka, Ranjan, Duggirala, Ravindranath, Faul, Jessica D, Garrett, Melanie E, Gharib, Sina A, Guo, Xiuqing, Hall, Michael E, Hawley, Nicola L, He, Jiang, Hobbs, Brian D, Hokanson, John E, Hsiung, Chao A, Hwang, Shih-Jen, Hyde, Thomas M, Irvin, Marguerite R, Jaffe, Andrew E, Johnson, Eric O, Kaplan, Robert, Kardia, Sharon LR, Kaufman, Joel D, Kelly, Tanika N, Kleinman, Joel E, Kooperberg, Charles, Lee, I-Te, Levy, Daniel, Lutz, Sharon M, Manichaikul, Ani W, Martin, Lisa W, Marx, Olivia, McGarvey, Stephen T, Minster, Ryan L, Moll, Matthew, Moussa, Karine A, Naseri, Take, North, Kari E, Oelsner, Elizabeth C, Peralta, Juan M, Peyser, Patricia A, Psaty, Bruce M, Rafaels, Nicholas, Raffield, Laura M, Reupena, Muagututi'a Sefuiva, Rich, Stephen S, Rotter, Jerome I, Schwartz, David A, Shadyab, Aladdin H, Sheu, Wayne H-H, Sims, Mario, Smith, Jennifer A, Sun, Xiao, Taylor, Kent D, Telen, Marilyn J, Watson, Harold, Weeks, Daniel E, Weir, David R, Yanek, Lisa R, Young, Kendra A, Young, Kristin L, Zhao, Wei, Hancock, Dana B, Jiang, Bibo, Vrieze, Scott, Liu, Dajiang J, Chen, Fang, Chen, Fang, Wang, Xingyan, Jang, Seon-Kyeong, Quach, Bryan C, Weissenkampen, J Dylan, Khunsriraksakul, Chachrit, Yang, Lina, Sauteraud, Renan, Albert, Christine M, Allred, Nicholette DD, Arnett, Donna K, Ashley-Koch, Allison E, Barnes, Kathleen C, Barr, R Graham, Becker, Diane M, Bielak, Lawrence F, Bis, Joshua C, Blangero, John, Boorgula, Meher Preethi, Chasman, Daniel I, Chavan, Sameer, Chen, Yii-Der I, Chuang, Lee-Ming, Correa, Adolfo, Curran, Joanne E, David, Sean P, Fuentes, Lisa de Las, Deka, Ranjan, Duggirala, Ravindranath, Faul, Jessica D, Garrett, Melanie E, Gharib, Sina A, Guo, Xiuqing, Hall, Michael E, Hawley, Nicola L, He, Jiang, Hobbs, Brian D, Hokanson, John E, Hsiung, Chao A, Hwang, Shih-Jen, Hyde, Thomas M, Irvin, Marguerite R, Jaffe, Andrew E, Johnson, Eric O, Kaplan, Robert, Kardia, Sharon LR, Kaufman, Joel D, Kelly, Tanika N, Kleinman, Joel E, Kooperberg, Charles, Lee, I-Te, Levy, Daniel, Lutz, Sharon M, Manichaikul, Ani W, Martin, Lisa W, Marx, Olivia, McGarvey, Stephen T, Minster, Ryan L, Moll, Matthew, Moussa, Karine A, Naseri, Take, North, Kari E, Oelsner, Elizabeth C, Peralta, Juan M, Peyser, Patricia A, Psaty, Bruce M, Rafaels, Nicholas, Raffield, Laura M, Reupena, Muagututi'a Sefuiva, Rich, Stephen S, Rotter, Jerome I, Schwartz, David A, Shadyab, Aladdin H, Sheu, Wayne H-H, Sims, Mario, Smith, Jennifer A, Sun, Xiao, Taylor, Kent D, Telen, Marilyn J, Watson, Harold, Weeks, Daniel E, Weir, David R, Yanek, Lisa R, Young, Kendra A, Young, Kristin L, Zhao, Wei, Hancock, Dana B, Jiang, Bibo, Vrieze, Scott, and Liu, Dajiang J
Abstract: Most transcriptome-wide association studies (TWASs) so far focus on European ancestry and lack diversity. To overcome this limitation, we aggregated genome-wide association study (GWAS) summary statistics, whole-genome sequences and expression quantitative trait locus (eQTL) data from diverse ancestries. We developed a new approach, TESLA (multi-ancestry integrative study using an optimal linear combination of association statistics), to integrate an eQTL dataset with a multi-ancestry GWAS. By exploiting shared phenotypic effects between ancestries and accommodating potential effect heterogeneities, TESLA improves power over other TWAS methods. When applied to tobacco use phenotypes, TESLA identified 273 new genes, up to 55% more compared with alternative TWAS methods. These hits and subsequent fine mapping using TESLA point to target genes with biological relevance. In silico drug-repurposing analyses highlight several drugs with known efficacy, including dextromethorphan and galantamine, and new drugs such as muscle relaxants that may be repurposed for treating nicotine addiction.
Published: 2023

10. A generalized covariate-adjusted top-scoring pair algorithm with applications to diabetic kidney disease stage classification in the Chronic Renal Insufficiency Cohort (CRIC) Study.

Author: Kwan, Brian, Kwan, Brian, Fuhrer, Tobias, Montemayor, Daniel, Fink, Jeffery C, He, Jiang, Hsu, Chi-Yuan, Messer, Karen, Nelson, Robert G, Pu, Minya, Ricardo, Ana C, Rincon-Choles, Hernan, Shah, Vallabh O, Ye, Hongping, Zhang, Jing, Sharma, Kumar, Natarajan, Loki, Kwan, Brian, Kwan, Brian, Fuhrer, Tobias, Montemayor, Daniel, Fink, Jeffery C, He, Jiang, Hsu, Chi-Yuan, Messer, Karen, Nelson, Robert G, Pu, Minya, Ricardo, Ana C, Rincon-Choles, Hernan, Shah, Vallabh O, Ye, Hongping, Zhang, Jing, Sharma, Kumar, and Natarajan, Loki
Abstract: BackgroundThe growing amount of high dimensional biomolecular data has spawned new statistical and computational models for risk prediction and disease classification. Yet, many of these methods do not yield biologically interpretable models, despite offering high classification accuracy. An exception, the top-scoring pair (TSP) algorithm derives parameter-free, biologically interpretable single pair decision rules that are accurate and robust in disease classification. However, standard TSP methods do not accommodate covariates that could heavily influence feature selection for the top-scoring pair. Herein, we propose a covariate-adjusted TSP method, which uses residuals from a regression of features on the covariates for identifying top scoring pairs. We conduct simulations and a data application to investigate our method, and compare it to existing classifiers, LASSO and random forests.ResultsOur simulations found that features that were highly correlated with clinical variables had high likelihood of being selected as top scoring pairs in the standard TSP setting. However, through residualization, our covariate-adjusted TSP was able to identify new top scoring pairs, that were largely uncorrelated with clinical variables. In the data application, using patients with diabetes (n = 977) selected for metabolomic profiling in the Chronic Renal Insufficiency Cohort (CRIC) study, the standard TSP algorithm identified (valine-betaine, dimethyl-arg) as the top-scoring metabolite pair for classifying diabetic kidney disease (DKD) severity, whereas the covariate-adjusted TSP method identified the pair (pipazethate, octaethylene glycol) as top-scoring. Valine-betaine and dimethyl-arg had, respectively, ≥ 0.4 absolute correlation with urine albumin and serum creatinine, known prognosticators of DKD. Thus without covariate-adjustment the top-scoring pair largely reflected known markers of disease severity, whereas covariate-adjusted TSP uncovered features liberated from conf
Published: 2023

11. Aberrant activation of TCL1A promotes stem cell expansion in clonal haematopoiesis.

Author: Weinstock, Joshua, Weinstock, Joshua, Gopakumar, Jayakrishnan, Burugula, Bala, Uddin, Md, Jahn, Nikolaus, Belk, Julia, Bouzid, Hind, Daniel, Bence, Miao, Zhuang, Ly, Nghi, Mack, Taralynn, Luna, Sofia, Prothro, Katherine, Mitchell, Shaneice, Laurie, Cecelia, Broome, Jai, Taylor, Kent, Guo, Xiuqing, Sinner, Moritz, von Falkenhausen, Aenne, Kääb, Stefan, Shuldiner, Alan, OConnell, Jeffrey, Lewis, Joshua, Boerwinkle, Eric, Barnes, Kathleen, Chami, Nathalie, Kenny, Eimear, Loos, Ruth, Fornage, Myriam, Hou, Lifang, Lloyd-Jones, Donald, Redline, Susan, Cade, Brian, Psaty, Bruce, Bis, Joshua, Brody, Jennifer, Silverman, Edwin, Yun, Jeong, Qiao, Dandi, Palmer, Nicholette, Freedman, Barry, Bowden, Donald, Cho, Michael, DeMeo, Dawn, Vasan, Ramachandran, Yanek, Lisa, Becker, Lewis, Kardia, Sharon, Peyser, Patricia, He, Jiang, Rienstra, Michiel, Van der Harst, Pim, Kaplan, Robert, Heckbert, Susan, Smith, Nicholas, Wiggins, Kerri, Arnett, Donna, Irvin, Marguerite, Tiwari, Hemant, Cutler, Michael, Knight, Stacey, Muhlestein, J, Correa, Adolfo, Raffield, Laura, Gao, Yan, de Andrade, Mariza, Rotter, Jerome, Rich, Stephen, Tracy, Russell, Konkle, Barbara, Johnsen, Jill, Wheeler, Marsha, Smith, J, Melander, Olle, Nilsson, Peter, Custer, Brian, Duggirala, Ravindranath, Curran, Joanne, Blangero, John, McGarvey, Stephen, Williams, L, Xiao, Shujie, Yang, Mao, Gu, C, Chen, Yii-Der, Lee, Wen-Jane, Kane, John, Pullinger, Clive, Shoemaker, M, Darbar, Dawood, Roden, Dan, Albert, Christine, Kooperberg, Charles, Zhou, Ying, Manson, JoAnn, Desai, Pinkal, Johnson, Andrew, Mathias, Rasika, Blackwell, Thomas, Weinstock, Joshua, Weinstock, Joshua, Gopakumar, Jayakrishnan, Burugula, Bala, Uddin, Md, Jahn, Nikolaus, Belk, Julia, Bouzid, Hind, Daniel, Bence, Miao, Zhuang, Ly, Nghi, Mack, Taralynn, Luna, Sofia, Prothro, Katherine, Mitchell, Shaneice, Laurie, Cecelia, Broome, Jai, Taylor, Kent, Guo, Xiuqing, Sinner, Moritz, von Falkenhausen, Aenne, Kääb, Stefan, Shuldiner, Alan, OConnell, Jeffrey, Lewis, Joshua, Boerwinkle, Eric, Barnes, Kathleen, Chami, Nathalie, Kenny, Eimear, Loos, Ruth, Fornage, Myriam, Hou, Lifang, Lloyd-Jones, Donald, Redline, Susan, Cade, Brian, Psaty, Bruce, Bis, Joshua, Brody, Jennifer, Silverman, Edwin, Yun, Jeong, Qiao, Dandi, Palmer, Nicholette, Freedman, Barry, Bowden, Donald, Cho, Michael, DeMeo, Dawn, Vasan, Ramachandran, Yanek, Lisa, Becker, Lewis, Kardia, Sharon, Peyser, Patricia, He, Jiang, Rienstra, Michiel, Van der Harst, Pim, Kaplan, Robert, Heckbert, Susan, Smith, Nicholas, Wiggins, Kerri, Arnett, Donna, Irvin, Marguerite, Tiwari, Hemant, Cutler, Michael, Knight, Stacey, Muhlestein, J, Correa, Adolfo, Raffield, Laura, Gao, Yan, de Andrade, Mariza, Rotter, Jerome, Rich, Stephen, Tracy, Russell, Konkle, Barbara, Johnsen, Jill, Wheeler, Marsha, Smith, J, Melander, Olle, Nilsson, Peter, Custer, Brian, Duggirala, Ravindranath, Curran, Joanne, Blangero, John, McGarvey, Stephen, Williams, L, Xiao, Shujie, Yang, Mao, Gu, C, Chen, Yii-Der, Lee, Wen-Jane, Kane, John, Pullinger, Clive, Shoemaker, M, Darbar, Dawood, Roden, Dan, Albert, Christine, Kooperberg, Charles, Zhou, Ying, Manson, JoAnn, Desai, Pinkal, Johnson, Andrew, Mathias, Rasika, and Blackwell, Thomas
Abstract: Mutations in a diverse set of driver genes increase the fitness of haematopoietic stem cells (HSCs), leading to clonal haematopoiesis1. These lesions are precursors for blood cancers2-6, but the basis of their fitness advantage remains largely unknown, partly owing to a paucity of large cohorts in which the clonal expansion rate has been assessed by longitudinal sampling. Here, to circumvent this limitation, we developed a method to infer the expansion rate from data from a single time point. We applied this method to 5,071 people with clonal haematopoiesis. A genome-wide association study revealed that a common inherited polymorphism in the TCL1A promoter was associated with a slower expansion rate in clonal haematopoiesis overall, but the effect varied by driver gene. Those carrying this protective allele exhibited markedly reduced growth rates or prevalence of clones with driver mutations in TET2, ASXL1, SF3B1 and SRSF2, but this effect was not seen in clones with driver mutations in DNMT3A. TCL1A was not expressed in normal or DNMT3A-mutated HSCs, but the introduction of mutations in TET2 or ASXL1 led to the expression of TCL1A protein and the expansion of HSCs in vitro. The protective allele restricted TCL1A expression and expansion of mutant HSCs, as did experimental knockdown of TCL1A expression. Forced expression of TCL1A promoted the expansion of human HSCs in vitro and mouse HSCs in vivo. Our results indicate that the fitness advantage of several commonly mutated driver genes in clonal haematopoiesis may be mediated by TCL1A activation.
Published: 2023

12. PCSK9 Promotes Hypoxia-Induced EC Pyroptosis by Regulating Smac Mitochondrion-Cytoplasm Translocation in Critical Limb Ischemia

Author: Zhang, Meixin, Chen, Yixi, Qiu, Yumin, Sun, Jiapan, He, Jiang, Liu, Zhefu, Shi, Jian, Wei, Wenbin, Wu, Guifu, Liang, Jianwen, Zhang, Meixin, Chen, Yixi, Qiu, Yumin, Sun, Jiapan, He, Jiang, Liu, Zhefu, Shi, Jian, Wei, Wenbin, Wu, Guifu, and Liang, Jianwen
Abstract: Hypoxia-induced endothelial cell death and impaired angiogenesis are the main pathophysiological features of critical limb ischemia. Mechanistically, proprotein convertase subtilisin/kexin type 9 (PCSK9) promoted Smac translocation from mitochondria to the cytoplasm. Inhibition of Smac release into the cytoplasm attenuated PCSK9-mediated hypoxia-induced pyroptosis. Functionally, PCSK9 overexpression impaired angiogenesis in vitro and reduced blood perfusion in mice with lower limb ischemia, but the effect was reversed by PCSK9 inhibition. This study demonstrates that PCSK9 aggravates pyroptosis by regulating Smac mitochondrion-cytoplasm translocation in the vascular endothelium, providing novel insights into PCSK9 as a potential therapeutic target in critical limb ischemia. © 2023 The Authors
Published: 2023

13. In-orbit background and sky survey simulation study of POLAR-2/LPD

Author: Feng, Zu-Ke, Liu, Hong-Bang, Xie, Fei, Feng, Huan-Bo, Mai, Qian-Nan, Tuo, Jiang-Chuan, Zhong, Qian, Sun, Jian-Chao, He, Jiang, Wang, Yuan-Hao, Liu, Qian, Yi, Di-Fan, Ma, Rui-Ting, Wang, Bin-Long, Tang, Zhen-Yu, Zhang, Shuang-Nan, Liang, En-Wei, Feng, Zu-Ke, Liu, Hong-Bang, Xie, Fei, Feng, Huan-Bo, Mai, Qian-Nan, Tuo, Jiang-Chuan, Zhong, Qian, Sun, Jian-Chao, He, Jiang, Wang, Yuan-Hao, Liu, Qian, Yi, Di-Fan, Ma, Rui-Ting, Wang, Bin-Long, Tang, Zhen-Yu, Zhang, Shuang-Nan, and Liang, En-Wei
Abstract: The Low-Energy X-ray Polarization Detector (LPD) is one of the payloads in the POLAR-2 experiment, designed as an external payload for the China Space Station (CSS) deployment in early 2024. LPD is specifically designed to observe the polarization of Gamma-Ray Bursts (GRBs) prompt emission in the energy range of 2-10 keV, with a wide field of view (FoV) of 90 degrees in preliminary design. This observation is achieved using an array of X-ray photoelectric polarimeters based on gas pixel detectors. Due to the wide FoV configuration, the in-orbit background count rate in the soft X-ray range is high, while GRBs themselves also exhibit a high flux in this energy band. In order to assess the contribution of various background components to the total count rate, we conducted detailed simulations using the GEANT4 C++ package. Our simulations encompassed the main interactions within the instrument materials and provided insights into various background components within the wide FoV scheme. The simulation results reveal that among the background components, the primary contributors are the cosmic X-ray background (CXB) and bright X-ray sources. The total background count rate of LPD, after applying the charged particle background rejection algorithm, is approximately 0.55 counts/cm^2/s on average, and it varies with the detector's orbit and pointing direction. Furthermore, we performed comprehensive simulations and comparative analyses of the CXB and X-ray bright sources under different FoVs and detector pointings. These analyses provide valuable insights into the background characteristic for soft X-ray polarimeter with wide FoV.
Published: 2023

14. Local-Global Temporal Difference Learning for Satellite Video Super-Resolution

Author: Xiao, Yi, Yuan, Qiangqiang, Jiang, Kui, Jin, Xianyu, He, Jiang, Zhang, Liangpei, Lin, Chia-wen, Xiao, Yi, Yuan, Qiangqiang, Jiang, Kui, Jin, Xianyu, He, Jiang, Zhang, Liangpei, and Lin, Chia-wen
Abstract: Optical-flow-based and kernel-based approaches have been extensively explored for temporal compensation in satellite Video Super-Resolution (VSR). However, these techniques are less generalized in large-scale or complex scenarios, especially in satellite videos. In this paper, we propose to exploit the well-defined temporal difference for efficient and effective temporal compensation. To fully utilize the local and global temporal information within frames, we systematically modeled the short-term and long-term temporal discrepancies since we observed that these discrepancies offer distinct and mutually complementary properties. Specifically, we devise a Short-term Temporal Difference Module (S-TDM) to extract local motion representations from RGB difference maps between adjacent frames, which yields more clues for accurate texture representation. To explore the global dependency in the entire frame sequence, a Long-term Temporal Difference Module (L-TDM) is proposed, where the differences between forward and backward segments are incorporated and activated to guide the modulation of the temporal feature, leading to a holistic global compensation. Moreover, we further propose a Difference Compensation Unit (DCU) to enrich the interaction between the spatial distribution of the target frame and temporal compensated results, which helps maintain spatial consistency while refining the features to avoid misalignment. Rigorous objective and subjective evaluations conducted across five mainstream video satellites demonstrate that our method performs favorably against state-of-the-art approaches. Code will be available at https://github.com/XY-boy/LGTD, Comment: Accepted by IEEE TCSVT
Published: 2023
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15. Including measures of chronic kidney disease to improve cardiovascular risk prediction by SCORE2 and SCORE2-OP

Author: Interne Geneeskunde Vasculaire, Nefro Vasculaire Geneeskunde, Circulatory Health, MS Interne Geneeskunde, Matsushita, Kunihiro, Kaptoge, Stephen, Hageman, Steven H.J., Sang, Yingying, Ballew, Shoshana H., Grams, Morgan E., Surapaneni, Aditya, Sun, Luanluan, Arnlov, Johan, Bozic, Milica, Brenner, Hermann, Brunskill, Nigel J., Chang, Alex R., Chinnadurai, Rajkumar, Cirillo, Massimo, Correa, Adolfo, Ebert, Natalie, Eckardt, Kai Uwe, Gansevoort, Ron T., Gutierrez, Orlando, Hadaegh, Farzad, He, Jiang, Hwang, Shih Jen, Jafar, Tazeen H., Jassal, Simerjot K., Kayama, Takamasa, Kovesdy, Csaba P., Landman, Gijs W., Levey, Andrew S., Lloyd-Jones, Donald M., Major, Rupert W., Miura, Katsuyuki, Muntner, Paul, Nadkarni, Girish N., Nowak, Christoph, Ohkubo, Takayoshi, Pena, Michelle J., Polkinghorne, Kevan R., Sairenchi, Toshimi, Schaeffner, Elke, Schneider, Markus P., Shalev, Varda, Shlipak, Michael G., Solbu, Marit D., Stempniewicz, Nikita, Tollitt, James, Valdivielso, José M., Van Der Leeuw, Joep, Dorresteijn, Jannick A.N., Visseren, Frank L.J., Interne Geneeskunde Vasculaire, Nefro Vasculaire Geneeskunde, Circulatory Health, MS Interne Geneeskunde, Matsushita, Kunihiro, Kaptoge, Stephen, Hageman, Steven H.J., Sang, Yingying, Ballew, Shoshana H., Grams, Morgan E., Surapaneni, Aditya, Sun, Luanluan, Arnlov, Johan, Bozic, Milica, Brenner, Hermann, Brunskill, Nigel J., Chang, Alex R., Chinnadurai, Rajkumar, Cirillo, Massimo, Correa, Adolfo, Ebert, Natalie, Eckardt, Kai Uwe, Gansevoort, Ron T., Gutierrez, Orlando, Hadaegh, Farzad, He, Jiang, Hwang, Shih Jen, Jafar, Tazeen H., Jassal, Simerjot K., Kayama, Takamasa, Kovesdy, Csaba P., Landman, Gijs W., Levey, Andrew S., Lloyd-Jones, Donald M., Major, Rupert W., Miura, Katsuyuki, Muntner, Paul, Nadkarni, Girish N., Nowak, Christoph, Ohkubo, Takayoshi, Pena, Michelle J., Polkinghorne, Kevan R., Sairenchi, Toshimi, Schaeffner, Elke, Schneider, Markus P., Shalev, Varda, Shlipak, Michael G., Solbu, Marit D., Stempniewicz, Nikita, Tollitt, James, Valdivielso, José M., Van Der Leeuw, Joep, Dorresteijn, Jannick A.N., and Visseren, Frank L.J.
Published: 2023

16. Rare variants in long non-coding RNAs are associated with blood lipid levels in the TOPMed whole-genome sequencing study.

Author: Wang, Yuxuan, Wang, Yuxuan, Selvaraj, Margaret, Li, Xihao, Li, Zilin, Holdcraft, Jacob, Arnett, Donna, Bis, Joshua, Blangero, John, Boerwinkle, Eric, Bowden, Donald, Cade, Brian, Carlson, Jenna, Carson, April, Chen, Yii-Der, Curran, Joanne, de Vries, Paul, Dutcher, Susan, Ellinor, Patrick, Floyd, James, Fornage, Myriam, Freedman, Barry, Gabriel, Stacey, Germer, Soren, Gibbs, Richard, Guo, Xiuqing, He, Jiang, Heard-Costa, Nancy, Hildalgo, Bertha, Hou, Lifang, Irvin, Marguerite, Joehanes, Roby, Kaplan, Robert, Kardia, Sharon, Kelly, Tanika, Kim, Ryan, Kooperberg, Charles, Kral, Brian, Levy, Daniel, Li, Changwei, Liu, Chunyu, Lloyd-Jone, Don, Loos, Ruth, Mahaney, Michael, Martin, Lisa, Mathias, Rasika, Minster, Ryan, Mitchell, Braxton, Montasser, May, Morrison, Alanna, Murabito, Joanne, Naseri, Take, OConnell, Jeffrey, Palmer, Nicholette, Preuss, Michael, Psaty, Bruce, Raffield, Laura, Rao, Dabeeru, Redline, Susan, Reiner, Alexander, Rich, Stephen, Ruepena, Muagututia, Sheu, Wayne, Smith, Jennifer, Smith, Albert, Tiwari, Hemant, Tsai, Michael, Viaud-Martinez, Karine, Wang, Zhe, Yanek, Lisa, Zhao, Wei, Lin, Xihong, Natarajan, Pradeep, Peloso, Gina, Rotter, Jerome, Wang, Yuxuan, Wang, Yuxuan, Selvaraj, Margaret, Li, Xihao, Li, Zilin, Holdcraft, Jacob, Arnett, Donna, Bis, Joshua, Blangero, John, Boerwinkle, Eric, Bowden, Donald, Cade, Brian, Carlson, Jenna, Carson, April, Chen, Yii-Der, Curran, Joanne, de Vries, Paul, Dutcher, Susan, Ellinor, Patrick, Floyd, James, Fornage, Myriam, Freedman, Barry, Gabriel, Stacey, Germer, Soren, Gibbs, Richard, Guo, Xiuqing, He, Jiang, Heard-Costa, Nancy, Hildalgo, Bertha, Hou, Lifang, Irvin, Marguerite, Joehanes, Roby, Kaplan, Robert, Kardia, Sharon, Kelly, Tanika, Kim, Ryan, Kooperberg, Charles, Kral, Brian, Levy, Daniel, Li, Changwei, Liu, Chunyu, Lloyd-Jone, Don, Loos, Ruth, Mahaney, Michael, Martin, Lisa, Mathias, Rasika, Minster, Ryan, Mitchell, Braxton, Montasser, May, Morrison, Alanna, Murabito, Joanne, Naseri, Take, OConnell, Jeffrey, Palmer, Nicholette, Preuss, Michael, Psaty, Bruce, Raffield, Laura, Rao, Dabeeru, Redline, Susan, Reiner, Alexander, Rich, Stephen, Ruepena, Muagututia, Sheu, Wayne, Smith, Jennifer, Smith, Albert, Tiwari, Hemant, Tsai, Michael, Viaud-Martinez, Karine, Wang, Zhe, Yanek, Lisa, Zhao, Wei, Lin, Xihong, Natarajan, Pradeep, Peloso, Gina, and Rotter, Jerome
Abstract: Long non-coding RNAs (lncRNAs) are known to perform important regulatory functions in lipid metabolism. Large-scale whole-genome sequencing (WGS) studies and new statistical methods for variant set tests now provide an opportunity to assess more associations between rare variants in lncRNA genes and complex traits across the genome. In this study, we used high-coverage WGS from 66,329 participants of diverse ancestries with measurement of blood lipids and lipoproteins (LDL-C, HDL-C, TC, and TG) in the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) program to investigate the role of lncRNAs in lipid variability. We aggregated rare variants for 165,375 lncRNA genes based on their genomic locations and conducted rare-variant aggregate association tests using the STAAR (variant-set test for association using annotation information) framework. We performed STAAR conditional analysis adjusting for common variants in known lipid GWAS loci and rare-coding variants in nearby protein-coding genes. Our analyses revealed 83 rare lncRNA variant sets significantly associated with blood lipid levels, all of which were located in known lipid GWAS loci (in a ±500-kb window of a Global Lipids Genetics Consortium index variant). Notably, 61 out of 83 signals (73%) were conditionally independent of common regulatory variation and rare protein-coding variation at the same loci. We replicated 34 out of 61 (56%) conditionally independent associations using the independent UK Biobank WGS data. Our results expand the genetic architecture of blood lipids to rare variants in lncRNAs.
Published: 2023

17. A statistical framework for powerful multi-trait rare variant analysis in large-scale whole-genome sequencing studies

Author: Li, Xihao, Chen, Han, Selvaraj, Margaret Sunitha, Van Buren, Eric, Zhou, Hufeng, Wang, Yuxuan, Sun, Ryan, McCaw, Zachary R, Yu, Zhi, Arnett, Donna K, Bis, Joshua C, Blangero, John, Boerwinkle, Eric, Bowden, Donald W, Brody, Jennifer A, Cade, Brian E, Carson, April P, Carlson, Jenna C, Chami, Nathalie, Chen, Yii-Der Ida, Curran, Joanne E, de Vries, Paul S, Fornage, Myriam, Franceschini, Nora, Freedman, Barry I, Gu, Charles, Heard-Costa, Nancy L, He, Jiang, Hou, Lifang, Hung, Yi-Jen, Irvin, Marguerite R, Kaplan, Robert C, Kardia, Sharon L R, Kelly, Tanika, Konigsberg, Iain, Kooperberg, Charles, Kral, Brian G, Li, Changwei, Loos, Ruth J F, Mahaney, Michael C, Martin, Lisa W, Mathias, Rasika A, Minster, Ryan L, Mitchell, Braxton D, Montasser, May E, Morrison, Alanna C, Palmer, Nicholette D, Peyser, Patricia A, Psaty, Bruce M, Raffield, Laura M, Li, Xihao, Chen, Han, Selvaraj, Margaret Sunitha, Van Buren, Eric, Zhou, Hufeng, Wang, Yuxuan, Sun, Ryan, McCaw, Zachary R, Yu, Zhi, Arnett, Donna K, Bis, Joshua C, Blangero, John, Boerwinkle, Eric, Bowden, Donald W, Brody, Jennifer A, Cade, Brian E, Carson, April P, Carlson, Jenna C, Chami, Nathalie, Chen, Yii-Der Ida, Curran, Joanne E, de Vries, Paul S, Fornage, Myriam, Franceschini, Nora, Freedman, Barry I, Gu, Charles, Heard-Costa, Nancy L, He, Jiang, Hou, Lifang, Hung, Yi-Jen, Irvin, Marguerite R, Kaplan, Robert C, Kardia, Sharon L R, Kelly, Tanika, Konigsberg, Iain, Kooperberg, Charles, Kral, Brian G, Li, Changwei, Loos, Ruth J F, Mahaney, Michael C, Martin, Lisa W, Mathias, Rasika A, Minster, Ryan L, Mitchell, Braxton D, Montasser, May E, Morrison, Alanna C, Palmer, Nicholette D, Peyser, Patricia A, Psaty, Bruce M, and Raffield, Laura M
Abstract: Large-scale whole-genome sequencing (WGS) studies have improved our understanding of the contributions of coding and noncoding rare variants to complex human traits. Leveraging association effect sizes across multiple traits in WGS rare variant association analysis can improve statistical power over single-trait analysis, and also detect pleiotropic genes and regions. Existing multi-trait methods have limited ability to perform rare variant analysis of large-scale WGS data. We propose MultiSTAAR, a statistical framework and computationally-scalable analytical pipeline for functionally-informed multi-trait rare variant analysis in large-scale WGS studies. MultiSTAAR accounts for relatedness, population structure and correlation among phenotypes by jointly analyzing multiple traits, and further empowers rare variant association analysis by incorporating multiple functional annotations. We applied MultiSTAAR to jointly analyze three lipid traits (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides) in 61,861 multi-ethnic samples from the Trans-Omics for Precision Medicine (TOPMed) Program. We discovered new associations with lipid traits missed by single-trait analysis, including rare variants within an enhancer of NIPSNAP3A and an intergenic region on chromosome 1.
Published: 2023

18. Rare variants in long non-coding RNAs are associated with blood lipid levels in the TOPMed whole-genome sequencing study

Author: Wang, Yuxuan, Selvaraj, Margaret Sunitha, Li, Xihao, Li, Zilin, Holdcraft, Jacob A., Arnett, Donna K., Bis, Joshua C., Blangero, John, Boerwinkle, Eric, Bowden, Donald W., Cade, Brian E., Carlson, Jenna C., Carson, April P., Chen, Yii Der Ida, Curran, Joanne E., de Vries, Paul S., Dutcher, Susan K., Ellinor, Patrick T., Floyd, James S., Fornage, Myriam, Freedman, Barry I., Gabriel, Stacey, Germer, Soren, Gibbs, Richard A., Guo, Xiuqing, He, Jiang, Heard-Costa, Nancy, Hildalgo, Bertha, Hou, Lifang, Irvin, Marguerite R., Joehanes, Roby, Kaplan, Robert C., Kardia, Sharon LR, Kelly, Tanika N., Kim, Ryan, Kooperberg, Charles, Kral, Brian G., Levy, Daniel, Li, Changwei, Liu, Chunyu, Lloyd-Jone, Don, Loos, Ruth J.F., Mahaney, Michael C., Martin, Lisa W., Mathias, Rasika A., Minster, Ryan L., Mitchell, Braxton D., Montasser, May E., Morrison, Alanna C., Murabito, Joanne M., Wang, Yuxuan, Selvaraj, Margaret Sunitha, Li, Xihao, Li, Zilin, Holdcraft, Jacob A., Arnett, Donna K., Bis, Joshua C., Blangero, John, Boerwinkle, Eric, Bowden, Donald W., Cade, Brian E., Carlson, Jenna C., Carson, April P., Chen, Yii Der Ida, Curran, Joanne E., de Vries, Paul S., Dutcher, Susan K., Ellinor, Patrick T., Floyd, James S., Fornage, Myriam, Freedman, Barry I., Gabriel, Stacey, Germer, Soren, Gibbs, Richard A., Guo, Xiuqing, He, Jiang, Heard-Costa, Nancy, Hildalgo, Bertha, Hou, Lifang, Irvin, Marguerite R., Joehanes, Roby, Kaplan, Robert C., Kardia, Sharon LR, Kelly, Tanika N., Kim, Ryan, Kooperberg, Charles, Kral, Brian G., Levy, Daniel, Li, Changwei, Liu, Chunyu, Lloyd-Jone, Don, Loos, Ruth J.F., Mahaney, Michael C., Martin, Lisa W., Mathias, Rasika A., Minster, Ryan L., Mitchell, Braxton D., Montasser, May E., Morrison, Alanna C., and Murabito, Joanne M.
Abstract: Long non-coding RNAs (lncRNAs) are known to perform important regulatory functions in lipid metabolism. Large-scale whole-genome sequencing (WGS) studies and new statistical methods for variant set tests now provide an opportunity to assess more associations between rare variants in lncRNA genes and complex traits across the genome. In this study, we used high-coverage WGS from 66,329 participants of diverse ancestries with measurement of blood lipids and lipoproteins (LDL-C, HDL-C, TC, and TG) in the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) program to investigate the role of lncRNAs in lipid variability. We aggregated rare variants for 165,375 lncRNA genes based on their genomic locations and conducted rare-variant aggregate association tests using the STAAR (variant-set test for association using annotation information) framework. We performed STAAR conditional analysis adjusting for common variants in known lipid GWAS loci and rare-coding variants in nearby protein-coding genes. Our analyses revealed 83 rare lncRNA variant sets significantly associated with blood lipid levels, all of which were located in known lipid GWAS loci (in a ±500-kb window of a Global Lipids Genetics Consortium index variant). Notably, 61 out of 83 signals (73%) were conditionally independent of common regulatory variation and rare protein-coding variation at the same loci. We replicated 34 out of 61 (56%) conditionally independent associations using the independent UK Biobank WGS data. Our results expand the genetic architecture of blood lipids to rare variants in lncRNAs.
Published: 2023

19. A statistical framework for powerful multi-trait rare variant analysis in large-scale whole-genome sequencing studies

Author: Li, Xihao, Chen, Han, Selvaraj, Margaret Sunitha, Van Buren, Eric, Zhou, Hufeng, Wang, Yuxuan, Sun, Ryan, McCaw, Zachary R, Yu, Zhi, Arnett, Donna K, Bis, Joshua C, Blangero, John, Boerwinkle, Eric, Bowden, Donald W, Brody, Jennifer A, Cade, Brian E, Carson, April P, Carlson, Jenna C, Chami, Nathalie, Chen, Yii-Der Ida, Curran, Joanne E, de Vries, Paul S, Fornage, Myriam, Franceschini, Nora, Freedman, Barry I, Gu, Charles, Heard-Costa, Nancy L, He, Jiang, Hou, Lifang, Hung, Yi-Jen, Irvin, Marguerite R, Kaplan, Robert C, Kardia, Sharon L R, Kelly, Tanika, Konigsberg, Iain, Kooperberg, Charles, Kral, Brian G, Li, Changwei, Loos, Ruth J F, Mahaney, Michael C, Martin, Lisa W, Mathias, Rasika A, Minster, Ryan L, Mitchell, Braxton D, Montasser, May E, Morrison, Alanna C, Palmer, Nicholette D, Peyser, Patricia A, Psaty, Bruce M, Raffield, Laura M, Li, Xihao, Chen, Han, Selvaraj, Margaret Sunitha, Van Buren, Eric, Zhou, Hufeng, Wang, Yuxuan, Sun, Ryan, McCaw, Zachary R, Yu, Zhi, Arnett, Donna K, Bis, Joshua C, Blangero, John, Boerwinkle, Eric, Bowden, Donald W, Brody, Jennifer A, Cade, Brian E, Carson, April P, Carlson, Jenna C, Chami, Nathalie, Chen, Yii-Der Ida, Curran, Joanne E, de Vries, Paul S, Fornage, Myriam, Franceschini, Nora, Freedman, Barry I, Gu, Charles, Heard-Costa, Nancy L, He, Jiang, Hou, Lifang, Hung, Yi-Jen, Irvin, Marguerite R, Kaplan, Robert C, Kardia, Sharon L R, Kelly, Tanika, Konigsberg, Iain, Kooperberg, Charles, Kral, Brian G, Li, Changwei, Loos, Ruth J F, Mahaney, Michael C, Martin, Lisa W, Mathias, Rasika A, Minster, Ryan L, Mitchell, Braxton D, Montasser, May E, Morrison, Alanna C, Palmer, Nicholette D, Peyser, Patricia A, Psaty, Bruce M, and Raffield, Laura M
Abstract: Large-scale whole-genome sequencing (WGS) studies have improved our understanding of the contributions of coding and noncoding rare variants to complex human traits. Leveraging association effect sizes across multiple traits in WGS rare variant association analysis can improve statistical power over single-trait analysis, and also detect pleiotropic genes and regions. Existing multi-trait methods have limited ability to perform rare variant analysis of large-scale WGS data. We propose MultiSTAAR, a statistical framework and computationally-scalable analytical pipeline for functionally-informed multi-trait rare variant analysis in large-scale WGS studies. MultiSTAAR accounts for relatedness, population structure and correlation among phenotypes by jointly analyzing multiple traits, and further empowers rare variant association analysis by incorporating multiple functional annotations. We applied MultiSTAAR to jointly analyze three lipid traits (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides) in 61,861 multi-ethnic samples from the Trans-Omics for Precision Medicine (TOPMed) Program. We discovered new associations with lipid traits missed by single-trait analysis, including rare variants within an enhancer of NIPSNAP3A and an intergenic region on chromosome 1.
Published: 2023

20. Rare variants in long non-coding RNAs are associated with blood lipid levels in the TOPMed whole-genome sequencing study

Author: Wang, Yuxuan, Selvaraj, Margaret Sunitha, Li, Xihao, Li, Zilin, Holdcraft, Jacob A., Arnett, Donna K., Bis, Joshua C., Blangero, John, Boerwinkle, Eric, Bowden, Donald W., Cade, Brian E., Carlson, Jenna C., Carson, April P., Chen, Yii Der Ida, Curran, Joanne E., de Vries, Paul S., Dutcher, Susan K., Ellinor, Patrick T., Floyd, James S., Fornage, Myriam, Freedman, Barry I., Gabriel, Stacey, Germer, Soren, Gibbs, Richard A., Guo, Xiuqing, He, Jiang, Heard-Costa, Nancy, Hildalgo, Bertha, Hou, Lifang, Irvin, Marguerite R., Joehanes, Roby, Kaplan, Robert C., Kardia, Sharon LR, Kelly, Tanika N., Kim, Ryan, Kooperberg, Charles, Kral, Brian G., Levy, Daniel, Li, Changwei, Liu, Chunyu, Lloyd-Jone, Don, Loos, Ruth J.F., Mahaney, Michael C., Martin, Lisa W., Mathias, Rasika A., Minster, Ryan L., Mitchell, Braxton D., Montasser, May E., Morrison, Alanna C., Murabito, Joanne M., Wang, Yuxuan, Selvaraj, Margaret Sunitha, Li, Xihao, Li, Zilin, Holdcraft, Jacob A., Arnett, Donna K., Bis, Joshua C., Blangero, John, Boerwinkle, Eric, Bowden, Donald W., Cade, Brian E., Carlson, Jenna C., Carson, April P., Chen, Yii Der Ida, Curran, Joanne E., de Vries, Paul S., Dutcher, Susan K., Ellinor, Patrick T., Floyd, James S., Fornage, Myriam, Freedman, Barry I., Gabriel, Stacey, Germer, Soren, Gibbs, Richard A., Guo, Xiuqing, He, Jiang, Heard-Costa, Nancy, Hildalgo, Bertha, Hou, Lifang, Irvin, Marguerite R., Joehanes, Roby, Kaplan, Robert C., Kardia, Sharon LR, Kelly, Tanika N., Kim, Ryan, Kooperberg, Charles, Kral, Brian G., Levy, Daniel, Li, Changwei, Liu, Chunyu, Lloyd-Jone, Don, Loos, Ruth J.F., Mahaney, Michael C., Martin, Lisa W., Mathias, Rasika A., Minster, Ryan L., Mitchell, Braxton D., Montasser, May E., Morrison, Alanna C., and Murabito, Joanne M.
Abstract: Long non-coding RNAs (lncRNAs) are known to perform important regulatory functions in lipid metabolism. Large-scale whole-genome sequencing (WGS) studies and new statistical methods for variant set tests now provide an opportunity to assess more associations between rare variants in lncRNA genes and complex traits across the genome. In this study, we used high-coverage WGS from 66,329 participants of diverse ancestries with measurement of blood lipids and lipoproteins (LDL-C, HDL-C, TC, and TG) in the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) program to investigate the role of lncRNAs in lipid variability. We aggregated rare variants for 165,375 lncRNA genes based on their genomic locations and conducted rare-variant aggregate association tests using the STAAR (variant-set test for association using annotation information) framework. We performed STAAR conditional analysis adjusting for common variants in known lipid GWAS loci and rare-coding variants in nearby protein-coding genes. Our analyses revealed 83 rare lncRNA variant sets significantly associated with blood lipid levels, all of which were located in known lipid GWAS loci (in a ±500-kb window of a Global Lipids Genetics Consortium index variant). Notably, 61 out of 83 signals (73%) were conditionally independent of common regulatory variation and rare protein-coding variation at the same loci. We replicated 34 out of 61 (56%) conditionally independent associations using the independent UK Biobank WGS data. Our results expand the genetic architecture of blood lipids to rare variants in lncRNAs.
Published: 2023

21. TDiffDe: A Truncated Diffusion Model for Remote Sensing Hyperspectral Image Denoising

Author: He, Jiang, Li, Yajie, L, Jie, Yuan, Qiangqiang, He, Jiang, Li, Yajie, L, Jie, and Yuan, Qiangqiang
Abstract: Hyperspectral images play a crucial role in precision agriculture, environmental monitoring or ecological analysis. However, due to sensor equipment and the imaging environment, the observed hyperspectral images are often inevitably corrupted by various noise. In this study, we proposed a truncated diffusion model, called TDiffDe, to recover the useful information in hyperspectral images gradually. Rather than starting from a pure noise, the input data contains image information in hyperspectral image denoising. Thus, we cut the trained diffusion model from small steps to avoid the destroy of valid information.
Published: 2023

22. EDiffSR: An Efficient Diffusion Probabilistic Model for Remote Sensing Image Super-Resolution

Author: Xiao, Yi, Yuan, Qiangqiang, Jiang, Kui, He, Jiang, Jin, Xianyu, Zhang, Liangpei, Xiao, Yi, Yuan, Qiangqiang, Jiang, Kui, He, Jiang, Jin, Xianyu, and Zhang, Liangpei
Abstract: Recently, convolutional networks have achieved remarkable development in remote sensing image Super-Resoltuion (SR) by minimizing the regression objectives, e.g., MSE loss. However, despite achieving impressive performance, these methods often suffer from poor visual quality with over-smooth issues. Generative adversarial networks have the potential to infer intricate details, but they are easy to collapse, resulting in undesirable artifacts. To mitigate these issues, in this paper, we first introduce Diffusion Probabilistic Model (DPM) for efficient remote sensing image SR, dubbed EDiffSR. EDiffSR is easy to train and maintains the merits of DPM in generating perceptual-pleasant images. Specifically, different from previous works using heavy UNet for noise prediction, we develop an Efficient Activation Network (EANet) to achieve favorable noise prediction performance by simplified channel attention and simple gate operation, which dramatically reduces the computational budget. Moreover, to introduce more valuable prior knowledge into the proposed EDiffSR, a practical Conditional Prior Enhancement Module (CPEM) is developed to help extract an enriched condition. Unlike most DPM-based SR models that directly generate conditions by amplifying LR images, the proposed CPEM helps to retain more informative cues for accurate SR. Extensive experiments on four remote sensing datasets demonstrate that EDiffSR can restore visual-pleasant images on simulated and real-world remote sensing images, both quantitatively and qualitatively. The code of EDiffSR will be available at https://github.com/XY-boy/EDiffSR, Comment: Submitted to IEEE TGRS
Published: 2023

23. Enhanced Catalytic Performance through in Situ Encapsulation of Ultrafine Ru Clusters within a High-Aluminum Zeolite

Author: Yang, Jiangqian, He, Ying, He, Jiang, Liu, Yuanshuai, Geng, Huawei, Chen, Shaohua, Lin, Lu, Liu, Meng, Chen, Tiehong, Jiang, Qike, Weckhuysen, Bert M., Luo, Wenhao, Wu, Zhijie, Yang, Jiangqian, He, Ying, He, Jiang, Liu, Yuanshuai, Geng, Huawei, Chen, Shaohua, Lin, Lu, Liu, Meng, Chen, Tiehong, Jiang, Qike, Weckhuysen, Bert M., Luo, Wenhao, and Wu, Zhijie
Abstract: Zeolite-encapsulated metal clusters have been shown to be an effective bifunctional catalyst for tandem catalysis. Nevertheless, the efficient encapsulation of nanometric metal species into a high-aluminum ZSM-5 zeolite still poses a significant challenge. In this contribution, we have prepared well-dispersed and ultra-small Ru clusters encapsulated within a high-aluminum ZSM-5 zeolite (with a Si/Al ratio of ∼30-40) via an in situ two-stage hydrothermal synthesis method. Small Ru clusters with an average size of ∼1 nm have been identified by scanning transmission electron microscopy and hydrogen chemisorption. Shape-selective hydrogenation experiments with different probe molecules reveal a predominant encapsulation (∼90%) of metal clusters within the MFI zeolite cavities, which significantly enhances thermal stability of metal clusters against sintering. 27Al magic angle spinning nuclear magnetic resonance and Brønsted acid site (BAS) titration experiments show the successful incorporation of aluminum species (>99%) into the zeolite framework and build-up of intimacy between the Ru clusters and BASs at a sub-nanometric level. The resulting Ru@H-ZSM-5 shows an enhanced activity and stability for the crucial hydrodeoxygenation (HDO) of phenol to cyclohexane, in biomass valorization. This synthesis strategy could be of great help for the rational design and development of zeolitic bifunctional catalysts and could be extended to other crystalline porous materials.
Published: 2022

24. NTIRE 2022 Spectral Recovery Challenge and Data Set

Author: Arad, B, Timofte, R, Yahel, R, Morag, N, Bernat, A, Cai, Y, Lin, J, Lin, Z, Wang, H, Zhang, Y, Pfister, H, Van Gool, L, Liu, S, Li, Y, Feng, C, Lei, L, Li, J, Du, S, Wu, C, Leng, Y, Song, R, Zhang, M, Song, C, Zhao, S, Lang, Z, Wei, W, Zhang, L, Dian, R, Shan, T, Guo, A, Liu, J, Agarla, M, Bianco, S, Buzzelli, M, Celona, L, Schettini, R, He, J, Xiao, Y, Xiao, J, Yuan, Q, Kwon, T, Ryu, D, Bae, H, Yang, H, Chang, H, Huang, Z, Chen, W, Kuo, S, Chen, J, Li, H, Sabarinathan, S, Uma, K, Bama, B, Roomi, S, Arad, Boaz, Timofte, Radu, Yahel, Rony, Morag, Nimrod, Bernat, Amir, Cai, Yuanhao, Lin, Jing, Lin, Zudi, Wang, Haoqian, Zhang, Yulun, Pfister, Hanspeter, Van Gool, Luc, Liu, Shuai, Li, Yongqiang, Feng, Chaoyu, Lei, Lei, Li, Jiaojiao, Du, Songcheng, Wu, Chaoxiong, Leng, Yihong, Song, Rui, Zhang, Mingwei, Song, Chongxing, Zhao, Shuyi, Lang, Zhiqiang, Wei, Wei, Zhang, Lei, Dian, Renwei, Shan, Tianci, Guo, Anjing, Feng, Chengguo, Liu, Jinyang, Agarla, Mirko, Bianco, Simone, Buzzelli, Marco, Celona, Luigi, Schettini, Raimondo, He, Jiang, Xiao, Yi, Xiao, Jiajun, Yuan, Qiangqiang, Li, Jie, Zhang, Liangpei, Kwon, Taesung, Ryu, Dohoon, Bae, Hyokyoung, Yang, Hao-Hsiang, Chang, Hua-En, Huang, Zhi-Kai, Chen, Wei-Ting, Kuo, Sy-Yen, Chen, Junyu, Li, Haiwei, Liu, Song, Sabarinathan, Sabarinathan, Bama, B Sathya, Roomi, S. Mohamed Mansoor, Arad, B, Timofte, R, Yahel, R, Morag, N, Bernat, A, Cai, Y, Lin, J, Lin, Z, Wang, H, Zhang, Y, Pfister, H, Van Gool, L, Liu, S, Li, Y, Feng, C, Lei, L, Li, J, Du, S, Wu, C, Leng, Y, Song, R, Zhang, M, Song, C, Zhao, S, Lang, Z, Wei, W, Zhang, L, Dian, R, Shan, T, Guo, A, Liu, J, Agarla, M, Bianco, S, Buzzelli, M, Celona, L, Schettini, R, He, J, Xiao, Y, Xiao, J, Yuan, Q, Kwon, T, Ryu, D, Bae, H, Yang, H, Chang, H, Huang, Z, Chen, W, Kuo, S, Chen, J, Li, H, Sabarinathan, S, Uma, K, Bama, B, Roomi, S, Arad, Boaz, Timofte, Radu, Yahel, Rony, Morag, Nimrod, Bernat, Amir, Cai, Yuanhao, Lin, Jing, Lin, Zudi, Wang, Haoqian, Zhang, Yulun, Pfister, Hanspeter, Van Gool, Luc, Liu, Shuai, Li, Yongqiang, Feng, Chaoyu, Lei, Lei, Li, Jiaojiao, Du, Songcheng, Wu, Chaoxiong, Leng, Yihong, Song, Rui, Zhang, Mingwei, Song, Chongxing, Zhao, Shuyi, Lang, Zhiqiang, Wei, Wei, Zhang, Lei, Dian, Renwei, Shan, Tianci, Guo, Anjing, Feng, Chengguo, Liu, Jinyang, Agarla, Mirko, Bianco, Simone, Buzzelli, Marco, Celona, Luigi, Schettini, Raimondo, He, Jiang, Xiao, Yi, Xiao, Jiajun, Yuan, Qiangqiang, Li, Jie, Zhang, Liangpei, Kwon, Taesung, Ryu, Dohoon, Bae, Hyokyoung, Yang, Hao-Hsiang, Chang, Hua-En, Huang, Zhi-Kai, Chen, Wei-Ting, Kuo, Sy-Yen, Chen, Junyu, Li, Haiwei, Liu, Song, Sabarinathan, Sabarinathan, Bama, B Sathya, and Roomi, S. Mohamed Mansoor
Abstract: This paper reviews the third biennial challenge on spectral reconstruction from RGB images, i.e., the recovery of whole-scene hyperspectral (HS) information from a 3-channel RGB image. This challenge presents the "ARAD_1K" data set: a new, larger-than-ever natural hyperspectral image data set containing 1,000 images. Challenge participants were required to recover hyper-spectral information from synthetically generated JPEG-compressed RGB images simulating capture by a known calibrated camera, operating under partially known parameters, in a setting which includes acquisition noise. The challenge was attended by 241 teams, with 60 teams com-peting in the final testing phase, 12 of which provided de-tailed descriptions of their methodology which are included in this report. The performance of these submissions is re-viewed and provided here as a gauge for the current state-of-the-art in spectral reconstruction from natural RGB images.
Published: 2022

25. Whole genome sequence association analysis of fasting glucose and fasting insulin levels in diverse cohorts from the NHLBI TOPMed program.

Author: DiCorpo, Daniel, DiCorpo, Daniel, Gaynor, Sheila M, Russell, Emily M, Westerman, Kenneth E, Raffield, Laura M, Majarian, Timothy D, Wu, Peitao, Sarnowski, Chloé, Highland, Heather M, Jackson, Anne, Hasbani, Natalie R, de Vries, Paul S, Brody, Jennifer A, Hidalgo, Bertha, Guo, Xiuqing, Perry, James A, O'Connell, Jeffrey R, Lent, Samantha, Montasser, May E, Cade, Brian E, Jain, Deepti, Wang, Heming, D'Oliveira Albanus, Ricardo, Varshney, Arushi, Yanek, Lisa R, Lange, Leslie, Palmer, Nicholette D, Almeida, Marcio, Peralta, Juan M, Aslibekyan, Stella, Baldridge, Abigail S, Bertoni, Alain G, Bielak, Lawrence F, Chen, Chung-Shiuan, Chen, Yii-Der Ida, Choi, Won Jung, Goodarzi, Mark O, Floyd, James S, Irvin, Marguerite R, Kalyani, Rita R, Kelly, Tanika N, Lee, Seonwook, Liu, Ching-Ti, Loesch, Douglas, Manson, JoAnn E, Minster, Ryan L, Naseri, Take, Pankow, James S, Rasmussen-Torvik, Laura J, Reiner, Alexander P, Reupena, Muagututi'a Sefuiva, Selvin, Elizabeth, Smith, Jennifer A, Weeks, Daniel E, Xu, Huichun, Yao, Jie, Zhao, Wei, Parker, Stephen, Alonso, Alvaro, Arnett, Donna K, Blangero, John, Boerwinkle, Eric, Correa, Adolfo, Cupples, L Adrienne, Curran, Joanne E, Duggirala, Ravindranath, He, Jiang, Heckbert, Susan R, Kardia, Sharon LR, Kim, Ryan W, Kooperberg, Charles, Liu, Simin, Mathias, Rasika A, McGarvey, Stephen T, Mitchell, Braxton D, Morrison, Alanna C, Peyser, Patricia A, Psaty, Bruce M, Redline, Susan, Shuldiner, Alan R, Taylor, Kent D, Vasan, Ramachandran S, Viaud-Martinez, Karine A, Florez, Jose C, Wilson, James G, Sladek, Robert, Rich, Stephen S, Rotter, Jerome I, Lin, Xihong, Dupuis, Josée, Meigs, James B, Wessel, Jennifer, Manning, Alisa K, DiCorpo, Daniel, DiCorpo, Daniel, Gaynor, Sheila M, Russell, Emily M, Westerman, Kenneth E, Raffield, Laura M, Majarian, Timothy D, Wu, Peitao, Sarnowski, Chloé, Highland, Heather M, Jackson, Anne, Hasbani, Natalie R, de Vries, Paul S, Brody, Jennifer A, Hidalgo, Bertha, Guo, Xiuqing, Perry, James A, O'Connell, Jeffrey R, Lent, Samantha, Montasser, May E, Cade, Brian E, Jain, Deepti, Wang, Heming, D'Oliveira Albanus, Ricardo, Varshney, Arushi, Yanek, Lisa R, Lange, Leslie, Palmer, Nicholette D, Almeida, Marcio, Peralta, Juan M, Aslibekyan, Stella, Baldridge, Abigail S, Bertoni, Alain G, Bielak, Lawrence F, Chen, Chung-Shiuan, Chen, Yii-Der Ida, Choi, Won Jung, Goodarzi, Mark O, Floyd, James S, Irvin, Marguerite R, Kalyani, Rita R, Kelly, Tanika N, Lee, Seonwook, Liu, Ching-Ti, Loesch, Douglas, Manson, JoAnn E, Minster, Ryan L, Naseri, Take, Pankow, James S, Rasmussen-Torvik, Laura J, Reiner, Alexander P, Reupena, Muagututi'a Sefuiva, Selvin, Elizabeth, Smith, Jennifer A, Weeks, Daniel E, Xu, Huichun, Yao, Jie, Zhao, Wei, Parker, Stephen, Alonso, Alvaro, Arnett, Donna K, Blangero, John, Boerwinkle, Eric, Correa, Adolfo, Cupples, L Adrienne, Curran, Joanne E, Duggirala, Ravindranath, He, Jiang, Heckbert, Susan R, Kardia, Sharon LR, Kim, Ryan W, Kooperberg, Charles, Liu, Simin, Mathias, Rasika A, McGarvey, Stephen T, Mitchell, Braxton D, Morrison, Alanna C, Peyser, Patricia A, Psaty, Bruce M, Redline, Susan, Shuldiner, Alan R, Taylor, Kent D, Vasan, Ramachandran S, Viaud-Martinez, Karine A, Florez, Jose C, Wilson, James G, Sladek, Robert, Rich, Stephen S, Rotter, Jerome I, Lin, Xihong, Dupuis, Josée, Meigs, James B, Wessel, Jennifer, and Manning, Alisa K
Abstract: The genetic determinants of fasting glucose (FG) and fasting insulin (FI) have been studied mostly through genome arrays, resulting in over 100 associated variants. We extended this work with high-coverage whole genome sequencing analyses from fifteen cohorts in NHLBI's Trans-Omics for Precision Medicine (TOPMed) program. Over 23,000 non-diabetic individuals from five race-ethnicities/populations (African, Asian, European, Hispanic and Samoan) were included. Eight variants were significantly associated with FG or FI across previously identified regions MTNR1B, G6PC2, GCK, GCKR and FOXA2. We additionally characterize suggestive associations with FG or FI near previously identified SLC30A8, TCF7L2, and ADCY5 regions as well as APOB, PTPRT, and ROBO1. Functional annotation resources including the Diabetes Epigenome Atlas were compiled for each signal (chromatin states, annotation principal components, and others) to elucidate variant-to-function hypotheses. We provide a catalog of nucleotide-resolution genomic variation spanning intergenic and intronic regions creating a foundation for future sequencing-based investigations of glycemic traits.
Published: 2022

26. The National Heart Lung and Blood Institute Disparities Elimination through Coordinated Interventions to Prevent and Control Heart and Lung Disease Alliance.

Author: Kho, Abel, Kho, Abel, Daumit, Gail L, Truesdale, Kimberly P, Brown, Arleen, Kilbourne, Amy M, Ladapo, Joseph, Wali, Soma, Cicutto, Lisa, Matthews, Alicia K, Smith, Justin D, Davis, Paris D, Schoenthaler, Antoinette, Ogedegbe, Gbenga, Islam, Nadia, Mills, Katherine T, He, Jiang, Watson, Karriem S, Winn, Robert A, Stevens, June, Huebschmann, Amy G, Szefler, Stanley J, Kho, Abel, Kho, Abel, Daumit, Gail L, Truesdale, Kimberly P, Brown, Arleen, Kilbourne, Amy M, Ladapo, Joseph, Wali, Soma, Cicutto, Lisa, Matthews, Alicia K, Smith, Justin D, Davis, Paris D, Schoenthaler, Antoinette, Ogedegbe, Gbenga, Islam, Nadia, Mills, Katherine T, He, Jiang, Watson, Karriem S, Winn, Robert A, Stevens, June, Huebschmann, Amy G, and Szefler, Stanley J
Abstract: ObjectiveTo describe the National Heart Lung and Blood Institute (NHLBI) sponsored Disparities Elimination through Coordinated Interventions to Prevent and Control Heart and Lung Disease (DECIPHeR) Alliance to support late-stage implementation research aimed at reducing disparities in communities with high burdens of cardiovascular and/or pulmonary disease.Study settingNHBLI funded seven DECIPHeR studies and a Coordinating Center. Projects target high-risk diverse populations including racial and ethnic minorities, urban, rural, and low-income communities, disadvantaged children, and persons with serious mental illness. Two projects address multiple cardiovascular risk factors, three focus on hypertension, one on tobacco use, and one on pediatric asthma.Study designThe initial phase supports planning activities for sustainable uptake of evidence-based interventions in targeted communities. The second phase tests late-stage evidence-based implementation strategies.Data collection/extraction methodsNot applicable.Principal findingsWe provide an overview of the DECIPHeR Alliance and individual study designs, populations, and settings, implementation strategies, interventions, and outcomes. We describe the Alliance's organizational structure, designed to promote cross-center partnership and collaboration.ConclusionsThe DECIPHeR Alliance represents an ambitious national effort to develop sustainable implementation of interventions to achieve cardiovascular and pulmonary health equity.
Published: 2022

27. Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of indeterminate potential.

Author: Nakao, Tetsushi, Nakao, Tetsushi, Bick, Alexander G, Taub, Margaret A, Zekavat, Seyedeh M, Uddin, Md M, Niroula, Abhishek, Carty, Cara L, Lane, John, Honigberg, Michael C, Weinstock, Joshua S, Pampana, Akhil, Gibson, Christopher J, Griffin, Gabriel K, Clarke, Shoa L, Bhattacharya, Romit, Assimes, Themistocles L, Emery, Leslie S, Stilp, Adrienne M, Wong, Quenna, Broome, Jai, Laurie, Cecelia A, Khan, Alyna T, Smith, Albert V, Blackwell, Thomas W, Codd, Veryan, Nelson, Christopher P, Yoneda, Zachary T, Peralta, Juan M, Bowden, Donald W, Irvin, Marguerite R, Boorgula, Meher, Zhao, Wei, Yanek, Lisa R, Wiggins, Kerri L, Hixson, James E, Gu, C Charles, Peloso, Gina M, Roden, Dan M, Reupena, Muagututi'a S, Hwu, Chii-Min, DeMeo, Dawn L, North, Kari E, Kelly, Shannon, Musani, Solomon K, Bis, Joshua C, Lloyd-Jones, Donald M, Johnsen, Jill M, Preuss, Michael, Tracy, Russell P, Peyser, Patricia A, Qiao, Dandi, Desai, Pinkal, Curran, Joanne E, Freedman, Barry I, Tiwari, Hemant K, Chavan, Sameer, Smith, Jennifer A, Smith, Nicholas L, Kelly, Tanika N, Hidalgo, Bertha, Cupples, L Adrienne, Weeks, Daniel E, Hawley, Nicola L, Minster, Ryan L, Samoan Obesity, Lifestyle and Genetic Adaptations Study (OLaGA) Group, Deka, Ranjan, Naseri, Take T, de Las Fuentes, Lisa, Raffield, Laura M, Morrison, Alanna C, Vries, Paul S, Ballantyne, Christie M, Kenny, Eimear E, Rich, Stephen S, Whitsel, Eric A, Cho, Michael H, Shoemaker, M Benjamin, Pace, Betty S, Blangero, John, Palmer, Nicholette D, Mitchell, Braxton D, Shuldiner, Alan R, Barnes, Kathleen C, Redline, Susan, Kardia, Sharon LR, Abecasis, Gonçalo R, Becker, Lewis C, Heckbert, Susan R, He, Jiang, Post, Wendy, Arnett, Donna K, Vasan, Ramachandran S, Darbar, Dawood, Weiss, Scott T, McGarvey, Stephen T, de Andrade, Mariza, Chen, Yii-Der Ida, Kaplan, Robert C, Meyers, Deborah A, Custer, Brian S, Nakao, Tetsushi, Nakao, Tetsushi, Bick, Alexander G, Taub, Margaret A, Zekavat, Seyedeh M, Uddin, Md M, Niroula, Abhishek, Carty, Cara L, Lane, John, Honigberg, Michael C, Weinstock, Joshua S, Pampana, Akhil, Gibson, Christopher J, Griffin, Gabriel K, Clarke, Shoa L, Bhattacharya, Romit, Assimes, Themistocles L, Emery, Leslie S, Stilp, Adrienne M, Wong, Quenna, Broome, Jai, Laurie, Cecelia A, Khan, Alyna T, Smith, Albert V, Blackwell, Thomas W, Codd, Veryan, Nelson, Christopher P, Yoneda, Zachary T, Peralta, Juan M, Bowden, Donald W, Irvin, Marguerite R, Boorgula, Meher, Zhao, Wei, Yanek, Lisa R, Wiggins, Kerri L, Hixson, James E, Gu, C Charles, Peloso, Gina M, Roden, Dan M, Reupena, Muagututi'a S, Hwu, Chii-Min, DeMeo, Dawn L, North, Kari E, Kelly, Shannon, Musani, Solomon K, Bis, Joshua C, Lloyd-Jones, Donald M, Johnsen, Jill M, Preuss, Michael, Tracy, Russell P, Peyser, Patricia A, Qiao, Dandi, Desai, Pinkal, Curran, Joanne E, Freedman, Barry I, Tiwari, Hemant K, Chavan, Sameer, Smith, Jennifer A, Smith, Nicholas L, Kelly, Tanika N, Hidalgo, Bertha, Cupples, L Adrienne, Weeks, Daniel E, Hawley, Nicola L, Minster, Ryan L, Samoan Obesity, Lifestyle and Genetic Adaptations Study (OLaGA) Group, Deka, Ranjan, Naseri, Take T, de Las Fuentes, Lisa, Raffield, Laura M, Morrison, Alanna C, Vries, Paul S, Ballantyne, Christie M, Kenny, Eimear E, Rich, Stephen S, Whitsel, Eric A, Cho, Michael H, Shoemaker, M Benjamin, Pace, Betty S, Blangero, John, Palmer, Nicholette D, Mitchell, Braxton D, Shuldiner, Alan R, Barnes, Kathleen C, Redline, Susan, Kardia, Sharon LR, Abecasis, Gonçalo R, Becker, Lewis C, Heckbert, Susan R, He, Jiang, Post, Wendy, Arnett, Donna K, Vasan, Ramachandran S, Darbar, Dawood, Weiss, Scott T, McGarvey, Stephen T, de Andrade, Mariza, Chen, Yii-Der Ida, Kaplan, Robert C, Meyers, Deborah A, and Custer, Brian S
Abstract: Human genetic studies support an inverse causal relationship between leukocyte telomere length (LTL) and coronary artery disease (CAD), but directionally mixed effects for LTL and diverse malignancies. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by expansion of hematopoietic cells bearing leukemogenic mutations, predisposes both hematologic malignancy and CAD. TERT (which encodes telomerase reverse transcriptase) is the most significantly associated germline locus for CHIP in genome-wide association studies. Here, we investigated the relationship between CHIP, LTL, and CAD in the Trans-Omics for Precision Medicine (TOPMed) program (n = 63,302) and UK Biobank (n = 47,080). Bidirectional Mendelian randomization studies were consistent with longer genetically imputed LTL increasing propensity to develop CHIP, but CHIP then, in turn, hastens to shorten measured LTL (mLTL). We also demonstrated evidence of modest mediation between CHIP and CAD by mLTL. Our data promote an understanding of potential causal relationships across CHIP and LTL toward prevention of CAD.
Published: 2022

28. Absence of long-term changes in urine biomarkers after AKI: findings from the CRIC study.

Author: McCoy, Ian E, McCoy, Ian E, Hsu, Jesse Y, Bonventre, Joseph V, Parikh, Chirag R, Go, Alan S, Liu, Kathleen D, Ricardo, Ana C, Srivastava, Anand, Cohen, Debbie L, He, Jiang, Chen, Jing, Rao, Panduranga S, Muiru, Anthony N, Hsu, Chi-Yuan, McCoy, Ian E, McCoy, Ian E, Hsu, Jesse Y, Bonventre, Joseph V, Parikh, Chirag R, Go, Alan S, Liu, Kathleen D, Ricardo, Ana C, Srivastava, Anand, Cohen, Debbie L, He, Jiang, Chen, Jing, Rao, Panduranga S, Muiru, Anthony N, and Hsu, Chi-Yuan
Abstract: BackgroundMechanisms by which AKI leads to CKD progression remain unclear. Several urine biomarkers have been identified as independent predictors of progressive CKD. It is unknown whether AKI may result in long-term changes in these urine biomarkers, which may mediate the effect of AKI on CKD progression.MethodsWe selected 198 episodes of hospitalized AKI (defined as peak/nadir inpatient serum creatinine values ≥ 1.5) among adult participants in the Chronic Renal Insufficiency Cohort (CRIC) Study. We matched the best non-AKI hospitalization (unique patients) for each AKI hospitalization using pre-hospitalization characteristics including eGFR and urine protein/creatinine ratio. Biomarkers were measured in banked urine samples collected at annual CRIC study visits.ResultsUrine biomarker measurements occurred a median of 7 months before and 5 months after hospitalization. There were no significant differences in the change in urine biomarker-to-creatinine ratio between the AKI and non-AKI groups: KIM-1/Cr + 9% vs + 7%, MCP-1/Cr + 4% vs + 1%, YKL-40/Cr + 7% vs -20%, EGF/Cr -11% vs -8%, UMOD/Cr -2% vs -7% and albumin/Cr + 17% vs + 13% (all p > 0.05).ConclusionIn this cohort of adults with CKD, AKI did not associate with long-term changes in urine biomarkers.
Published: 2022

29. The National Heart Lung and Blood Institute Disparities Elimination through Coordinated Interventions to Prevent and Control Heart and Lung Disease Alliance.

Author: Kho, Abel, Kho, Abel, Daumit, Gail L, Truesdale, Kimberly P, Brown, Arleen, Kilbourne, Amy M, Ladapo, Joseph, Wali, Soma, Cicutto, Lisa, Matthews, Alicia K, Smith, Justin D, Davis, Paris D, Schoenthaler, Antoinette, Ogedegbe, Gbenga, Islam, Nadia, Mills, Katherine T, He, Jiang, Watson, Karriem S, Winn, Robert A, Stevens, June, Huebschmann, Amy G, Szefler, Stanley J, Kho, Abel, Kho, Abel, Daumit, Gail L, Truesdale, Kimberly P, Brown, Arleen, Kilbourne, Amy M, Ladapo, Joseph, Wali, Soma, Cicutto, Lisa, Matthews, Alicia K, Smith, Justin D, Davis, Paris D, Schoenthaler, Antoinette, Ogedegbe, Gbenga, Islam, Nadia, Mills, Katherine T, He, Jiang, Watson, Karriem S, Winn, Robert A, Stevens, June, Huebschmann, Amy G, and Szefler, Stanley J
Abstract: ObjectiveTo describe the National Heart Lung and Blood Institute (NHLBI) sponsored Disparities Elimination through Coordinated Interventions to Prevent and Control Heart and Lung Disease (DECIPHeR) Alliance to support late-stage implementation research aimed at reducing disparities in communities with high burdens of cardiovascular and/or pulmonary disease.Study settingNHBLI funded seven DECIPHeR studies and a Coordinating Center. Projects target high-risk diverse populations including racial and ethnic minorities, urban, rural, and low-income communities, disadvantaged children, and persons with serious mental illness. Two projects address multiple cardiovascular risk factors, three focus on hypertension, one on tobacco use, and one on pediatric asthma.Study designThe initial phase supports planning activities for sustainable uptake of evidence-based interventions in targeted communities. The second phase tests late-stage evidence-based implementation strategies.Data collection/extraction methodsNot applicable.Principal findingsWe provide an overview of the DECIPHeR Alliance and individual study designs, populations, and settings, implementation strategies, interventions, and outcomes. We describe the Alliance's organizational structure, designed to promote cross-center partnership and collaboration.ConclusionsThe DECIPHeR Alliance represents an ambitious national effort to develop sustainable implementation of interventions to achieve cardiovascular and pulmonary health equity.
Published: 2022

30. Whole genome sequence association analysis of fasting glucose and fasting insulin levels in diverse cohorts from the NHLBI TOPMed program.

Author: DiCorpo, Daniel, DiCorpo, Daniel, Gaynor, Sheila M, Russell, Emily M, Westerman, Kenneth E, Raffield, Laura M, Majarian, Timothy D, Wu, Peitao, Sarnowski, Chloé, Highland, Heather M, Jackson, Anne, Hasbani, Natalie R, de Vries, Paul S, Brody, Jennifer A, Hidalgo, Bertha, Guo, Xiuqing, Perry, James A, O'Connell, Jeffrey R, Lent, Samantha, Montasser, May E, Cade, Brian E, Jain, Deepti, Wang, Heming, D'Oliveira Albanus, Ricardo, Varshney, Arushi, Yanek, Lisa R, Lange, Leslie, Palmer, Nicholette D, Almeida, Marcio, Peralta, Juan M, Aslibekyan, Stella, Baldridge, Abigail S, Bertoni, Alain G, Bielak, Lawrence F, Chen, Chung-Shiuan, Chen, Yii-Der Ida, Choi, Won Jung, Goodarzi, Mark O, Floyd, James S, Irvin, Marguerite R, Kalyani, Rita R, Kelly, Tanika N, Lee, Seonwook, Liu, Ching-Ti, Loesch, Douglas, Manson, JoAnn E, Minster, Ryan L, Naseri, Take, Pankow, James S, Rasmussen-Torvik, Laura J, Reiner, Alexander P, Reupena, Muagututi'a Sefuiva, Selvin, Elizabeth, Smith, Jennifer A, Weeks, Daniel E, Xu, Huichun, Yao, Jie, Zhao, Wei, Parker, Stephen, Alonso, Alvaro, Arnett, Donna K, Blangero, John, Boerwinkle, Eric, Correa, Adolfo, Cupples, L Adrienne, Curran, Joanne E, Duggirala, Ravindranath, He, Jiang, Heckbert, Susan R, Kardia, Sharon LR, Kim, Ryan W, Kooperberg, Charles, Liu, Simin, Mathias, Rasika A, McGarvey, Stephen T, Mitchell, Braxton D, Morrison, Alanna C, Peyser, Patricia A, Psaty, Bruce M, Redline, Susan, Shuldiner, Alan R, Taylor, Kent D, Vasan, Ramachandran S, Viaud-Martinez, Karine A, Florez, Jose C, Wilson, James G, Sladek, Robert, Rich, Stephen S, Rotter, Jerome I, Lin, Xihong, Dupuis, Josée, Meigs, James B, Wessel, Jennifer, Manning, Alisa K, DiCorpo, Daniel, DiCorpo, Daniel, Gaynor, Sheila M, Russell, Emily M, Westerman, Kenneth E, Raffield, Laura M, Majarian, Timothy D, Wu, Peitao, Sarnowski, Chloé, Highland, Heather M, Jackson, Anne, Hasbani, Natalie R, de Vries, Paul S, Brody, Jennifer A, Hidalgo, Bertha, Guo, Xiuqing, Perry, James A, O'Connell, Jeffrey R, Lent, Samantha, Montasser, May E, Cade, Brian E, Jain, Deepti, Wang, Heming, D'Oliveira Albanus, Ricardo, Varshney, Arushi, Yanek, Lisa R, Lange, Leslie, Palmer, Nicholette D, Almeida, Marcio, Peralta, Juan M, Aslibekyan, Stella, Baldridge, Abigail S, Bertoni, Alain G, Bielak, Lawrence F, Chen, Chung-Shiuan, Chen, Yii-Der Ida, Choi, Won Jung, Goodarzi, Mark O, Floyd, James S, Irvin, Marguerite R, Kalyani, Rita R, Kelly, Tanika N, Lee, Seonwook, Liu, Ching-Ti, Loesch, Douglas, Manson, JoAnn E, Minster, Ryan L, Naseri, Take, Pankow, James S, Rasmussen-Torvik, Laura J, Reiner, Alexander P, Reupena, Muagututi'a Sefuiva, Selvin, Elizabeth, Smith, Jennifer A, Weeks, Daniel E, Xu, Huichun, Yao, Jie, Zhao, Wei, Parker, Stephen, Alonso, Alvaro, Arnett, Donna K, Blangero, John, Boerwinkle, Eric, Correa, Adolfo, Cupples, L Adrienne, Curran, Joanne E, Duggirala, Ravindranath, He, Jiang, Heckbert, Susan R, Kardia, Sharon LR, Kim, Ryan W, Kooperberg, Charles, Liu, Simin, Mathias, Rasika A, McGarvey, Stephen T, Mitchell, Braxton D, Morrison, Alanna C, Peyser, Patricia A, Psaty, Bruce M, Redline, Susan, Shuldiner, Alan R, Taylor, Kent D, Vasan, Ramachandran S, Viaud-Martinez, Karine A, Florez, Jose C, Wilson, James G, Sladek, Robert, Rich, Stephen S, Rotter, Jerome I, Lin, Xihong, Dupuis, Josée, Meigs, James B, Wessel, Jennifer, and Manning, Alisa K
Abstract: The genetic determinants of fasting glucose (FG) and fasting insulin (FI) have been studied mostly through genome arrays, resulting in over 100 associated variants. We extended this work with high-coverage whole genome sequencing analyses from fifteen cohorts in NHLBI's Trans-Omics for Precision Medicine (TOPMed) program. Over 23,000 non-diabetic individuals from five race-ethnicities/populations (African, Asian, European, Hispanic and Samoan) were included. Eight variants were significantly associated with FG or FI across previously identified regions MTNR1B, G6PC2, GCK, GCKR and FOXA2. We additionally characterize suggestive associations with FG or FI near previously identified SLC30A8, TCF7L2, and ADCY5 regions as well as APOB, PTPRT, and ROBO1. Functional annotation resources including the Diabetes Epigenome Atlas were compiled for each signal (chromatin states, annotation principal components, and others) to elucidate variant-to-function hypotheses. We provide a catalog of nucleotide-resolution genomic variation spanning intergenic and intronic regions creating a foundation for future sequencing-based investigations of glycemic traits.
Published: 2022

31. Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of indeterminate potential.

Author: Nakao, Tetsushi, Nakao, Tetsushi, Bick, Alexander G, Taub, Margaret A, Zekavat, Seyedeh M, Uddin, Md M, Niroula, Abhishek, Carty, Cara L, Lane, John, Honigberg, Michael C, Weinstock, Joshua S, Pampana, Akhil, Gibson, Christopher J, Griffin, Gabriel K, Clarke, Shoa L, Bhattacharya, Romit, Assimes, Themistocles L, Emery, Leslie S, Stilp, Adrienne M, Wong, Quenna, Broome, Jai, Laurie, Cecelia A, Khan, Alyna T, Smith, Albert V, Blackwell, Thomas W, Codd, Veryan, Nelson, Christopher P, Yoneda, Zachary T, Peralta, Juan M, Bowden, Donald W, Irvin, Marguerite R, Boorgula, Meher, Zhao, Wei, Yanek, Lisa R, Wiggins, Kerri L, Hixson, James E, Gu, C Charles, Peloso, Gina M, Roden, Dan M, Reupena, Muagututi'a S, Hwu, Chii-Min, DeMeo, Dawn L, North, Kari E, Kelly, Shannon, Musani, Solomon K, Bis, Joshua C, Lloyd-Jones, Donald M, Johnsen, Jill M, Preuss, Michael, Tracy, Russell P, Peyser, Patricia A, Qiao, Dandi, Desai, Pinkal, Curran, Joanne E, Freedman, Barry I, Tiwari, Hemant K, Chavan, Sameer, Smith, Jennifer A, Smith, Nicholas L, Kelly, Tanika N, Hidalgo, Bertha, Cupples, L Adrienne, Weeks, Daniel E, Hawley, Nicola L, Minster, Ryan L, Samoan Obesity, Lifestyle and Genetic Adaptations Study (OLaGA) Group, Deka, Ranjan, Naseri, Take T, de Las Fuentes, Lisa, Raffield, Laura M, Morrison, Alanna C, Vries, Paul S, Ballantyne, Christie M, Kenny, Eimear E, Rich, Stephen S, Whitsel, Eric A, Cho, Michael H, Shoemaker, M Benjamin, Pace, Betty S, Blangero, John, Palmer, Nicholette D, Mitchell, Braxton D, Shuldiner, Alan R, Barnes, Kathleen C, Redline, Susan, Kardia, Sharon LR, Abecasis, Gonçalo R, Becker, Lewis C, Heckbert, Susan R, He, Jiang, Post, Wendy, Arnett, Donna K, Vasan, Ramachandran S, Darbar, Dawood, Weiss, Scott T, McGarvey, Stephen T, de Andrade, Mariza, Chen, Yii-Der Ida, Kaplan, Robert C, Meyers, Deborah A, Custer, Brian S, Nakao, Tetsushi, Nakao, Tetsushi, Bick, Alexander G, Taub, Margaret A, Zekavat, Seyedeh M, Uddin, Md M, Niroula, Abhishek, Carty, Cara L, Lane, John, Honigberg, Michael C, Weinstock, Joshua S, Pampana, Akhil, Gibson, Christopher J, Griffin, Gabriel K, Clarke, Shoa L, Bhattacharya, Romit, Assimes, Themistocles L, Emery, Leslie S, Stilp, Adrienne M, Wong, Quenna, Broome, Jai, Laurie, Cecelia A, Khan, Alyna T, Smith, Albert V, Blackwell, Thomas W, Codd, Veryan, Nelson, Christopher P, Yoneda, Zachary T, Peralta, Juan M, Bowden, Donald W, Irvin, Marguerite R, Boorgula, Meher, Zhao, Wei, Yanek, Lisa R, Wiggins, Kerri L, Hixson, James E, Gu, C Charles, Peloso, Gina M, Roden, Dan M, Reupena, Muagututi'a S, Hwu, Chii-Min, DeMeo, Dawn L, North, Kari E, Kelly, Shannon, Musani, Solomon K, Bis, Joshua C, Lloyd-Jones, Donald M, Johnsen, Jill M, Preuss, Michael, Tracy, Russell P, Peyser, Patricia A, Qiao, Dandi, Desai, Pinkal, Curran, Joanne E, Freedman, Barry I, Tiwari, Hemant K, Chavan, Sameer, Smith, Jennifer A, Smith, Nicholas L, Kelly, Tanika N, Hidalgo, Bertha, Cupples, L Adrienne, Weeks, Daniel E, Hawley, Nicola L, Minster, Ryan L, Samoan Obesity, Lifestyle and Genetic Adaptations Study (OLaGA) Group, Deka, Ranjan, Naseri, Take T, de Las Fuentes, Lisa, Raffield, Laura M, Morrison, Alanna C, Vries, Paul S, Ballantyne, Christie M, Kenny, Eimear E, Rich, Stephen S, Whitsel, Eric A, Cho, Michael H, Shoemaker, M Benjamin, Pace, Betty S, Blangero, John, Palmer, Nicholette D, Mitchell, Braxton D, Shuldiner, Alan R, Barnes, Kathleen C, Redline, Susan, Kardia, Sharon LR, Abecasis, Gonçalo R, Becker, Lewis C, Heckbert, Susan R, He, Jiang, Post, Wendy, Arnett, Donna K, Vasan, Ramachandran S, Darbar, Dawood, Weiss, Scott T, McGarvey, Stephen T, de Andrade, Mariza, Chen, Yii-Der Ida, Kaplan, Robert C, Meyers, Deborah A, and Custer, Brian S
Abstract: Human genetic studies support an inverse causal relationship between leukocyte telomere length (LTL) and coronary artery disease (CAD), but directionally mixed effects for LTL and diverse malignancies. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by expansion of hematopoietic cells bearing leukemogenic mutations, predisposes both hematologic malignancy and CAD. TERT (which encodes telomerase reverse transcriptase) is the most significantly associated germline locus for CHIP in genome-wide association studies. Here, we investigated the relationship between CHIP, LTL, and CAD in the Trans-Omics for Precision Medicine (TOPMed) program (n = 63,302) and UK Biobank (n = 47,080). Bidirectional Mendelian randomization studies were consistent with longer genetically imputed LTL increasing propensity to develop CHIP, but CHIP then, in turn, hastens to shorten measured LTL (mLTL). We also demonstrated evidence of modest mediation between CHIP and CAD by mLTL. Our data promote an understanding of potential causal relationships across CHIP and LTL toward prevention of CAD.
Published: 2022

32. Enhanced Catalytic Performance through in Situ Encapsulation of Ultrafine Ru Clusters within a High-Aluminum Zeolite

Author: Sub Inorganic Chemistry and Catalysis, Faculteit Betawetenschappen, Inorganic Chemistry and Catalysis, Yang, Jiangqian, He, Ying, He, Jiang, Liu, Yuanshuai, Geng, Huawei, Chen, Shaohua, Lin, Lu, Liu, Meng, Chen, Tiehong, Jiang, Qike, Weckhuysen, Bert M., Luo, Wenhao, Wu, Zhijie, Sub Inorganic Chemistry and Catalysis, Faculteit Betawetenschappen, Inorganic Chemistry and Catalysis, Yang, Jiangqian, He, Ying, He, Jiang, Liu, Yuanshuai, Geng, Huawei, Chen, Shaohua, Lin, Lu, Liu, Meng, Chen, Tiehong, Jiang, Qike, Weckhuysen, Bert M., Luo, Wenhao, and Wu, Zhijie
Published: 2022

33. Plasma Kidney Injury Molecule 1 in CKD: Findings From the Boston Kidney Biopsy Cohort and CRIC Studies.

Author: Schmidt, Insa M, Schmidt, Insa M, Srivastava, Anand, Sabbisetti, Venkata, McMahon, Gearoid M, He, Jiang, Chen, Jing, Kusek, John W, Taliercio, Jonathan, Ricardo, Ana C, Hsu, Chi-Yuan, Kimmel, Paul L, Liu, Kathleen D, Mifflin, Theodore E, Nelson, Robert G, Vasan, Ramachandran S, Xie, Dawei, Zhang, Xiaoming, Palsson, Ragnar, Stillman, Isaac E, Rennke, Helmut G, Feldman, Harold I, Bonventre, Joseph V, Waikar, Sushrut S, Chronic Kidney Disease Biomarkers Consortium and the CRIC Study Investigators, Schmidt, Insa M, Schmidt, Insa M, Srivastava, Anand, Sabbisetti, Venkata, McMahon, Gearoid M, He, Jiang, Chen, Jing, Kusek, John W, Taliercio, Jonathan, Ricardo, Ana C, Hsu, Chi-Yuan, Kimmel, Paul L, Liu, Kathleen D, Mifflin, Theodore E, Nelson, Robert G, Vasan, Ramachandran S, Xie, Dawei, Zhang, Xiaoming, Palsson, Ragnar, Stillman, Isaac E, Rennke, Helmut G, Feldman, Harold I, Bonventre, Joseph V, Waikar, Sushrut S, and Chronic Kidney Disease Biomarkers Consortium and the CRIC Study Investigators
Abstract: Rationale & objectivePlasma kidney injury molecule 1 (KIM-1) is a sensitive marker of proximal tubule injury, but its association with risks of adverse clinical outcomes across a spectrum of kidney diseases is unknown.Study designProspective, observational cohort study.Setting & participants524 individuals enrolled into the Boston Kidney Biopsy Cohort (BKBC) Study undergoing clinically indicated native kidney biopsy with biopsy specimens adjudicated for semiquantitative scores of histopathology by 2 kidney pathologists and 3,800 individuals with common forms of chronic kidney disease (CKD) enrolled into the Chronic Renal Insufficiency Cohort (CRIC) Study.ExposureHistopathologic lesions and clinicopathologic diagnosis in cross-sectional analyses, baseline plasma KIM-1 levels in prospective analyses.OutcomesBaseline plasma KIM-1 levels in cross-sectional analyses, kidney failure (defined as initiation of kidney replacement therapy) and death in prospective analyses.Analytical approachMultivariable-adjusted linear regression models tested associations of plasma KIM-1 levels with histopathologic lesions and clinicopathologic diagnoses. Cox proportional hazards models tested associations of plasma KIM-1 levels with future kidney failure and death.ResultsIn the BKBC Study, higher plasma KIM-1 levels were associated with more severe acute tubular injury, tubulointerstitial inflammation, and more severe mesangial expansion after multivariable adjustment. Participants with diabetic nephropathy, glomerulopathies, and tubulointerstitial disease had significantly higher plasma KIM-1 levels after multivariable adjustment. In the BKBC Study, CKD in 124 participants progressed to kidney failure and 85 participants died during a median follow-up time of 5 years. In the CRIC Study, CKD in 1,153 participants progressed to kidney failure and 1,356 participants died during a median follow-up time of 11.5 years. In both cohorts, each doubling of plasma KIM-1 level was assoc
Published: 2022

34. Whole genome sequence analysis of blood lipid levels in >66,000 individuals.

Author: Selvaraj, Margaret Sunitha, Selvaraj, Margaret Sunitha, Li, Xihao, Li, Zilin, Pampana, Akhil, Zhang, David Y, Park, Joseph, Aslibekyan, Stella, Bis, Joshua C, Brody, Jennifer A, Cade, Brian E, Chuang, Lee-Ming, Chung, Ren-Hua, Curran, Joanne E, de Las Fuentes, Lisa, de Vries, Paul S, Duggirala, Ravindranath, Freedman, Barry I, Graff, Mariaelisa, Guo, Xiuqing, Heard-Costa, Nancy, Hidalgo, Bertha, Hwu, Chii-Min, Irvin, Marguerite R, Kelly, Tanika N, Kral, Brian G, Lange, Leslie, Li, Xiaohui, Lisa, Martin, Lubitz, Steven A, Manichaikul, Ani W, Michael, Preuss, Montasser, May E, Morrison, Alanna C, Naseri, Take, O'Connell, Jeffrey R, Palmer, Nicholette D, Peyser, Patricia A, Reupena, Muagututia S, Smith, Jennifer A, Sun, Xiao, Taylor, Kent D, Tracy, Russell P, Tsai, Michael Y, Wang, Zhe, Wang, Yuxuan, Bao, Wei, Wilkins, John T, Yanek, Lisa R, Zhao, Wei, Arnett, Donna K, Blangero, John, Boerwinkle, Eric, Bowden, Donald W, Chen, Yii-Der Ida, Correa, Adolfo, Cupples, L Adrienne, Dutcher, Susan K, Ellinor, Patrick T, Fornage, Myriam, Gabriel, Stacey, Germer, Soren, Gibbs, Richard, He, Jiang, Kaplan, Robert C, Kardia, Sharon LR, Kim, Ryan, Kooperberg, Charles, Loos, Ruth JF, Viaud-Martinez, Karine A, Mathias, Rasika A, McGarvey, Stephen T, Mitchell, Braxton D, Nickerson, Deborah, North, Kari E, Psaty, Bruce M, Redline, Susan, Reiner, Alexander P, Vasan, Ramachandran S, Rich, Stephen S, Willer, Cristen, Rotter, Jerome I, Rader, Daniel J, Lin, Xihong, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Peloso, Gina M, Natarajan, Pradeep, Selvaraj, Margaret Sunitha, Selvaraj, Margaret Sunitha, Li, Xihao, Li, Zilin, Pampana, Akhil, Zhang, David Y, Park, Joseph, Aslibekyan, Stella, Bis, Joshua C, Brody, Jennifer A, Cade, Brian E, Chuang, Lee-Ming, Chung, Ren-Hua, Curran, Joanne E, de Las Fuentes, Lisa, de Vries, Paul S, Duggirala, Ravindranath, Freedman, Barry I, Graff, Mariaelisa, Guo, Xiuqing, Heard-Costa, Nancy, Hidalgo, Bertha, Hwu, Chii-Min, Irvin, Marguerite R, Kelly, Tanika N, Kral, Brian G, Lange, Leslie, Li, Xiaohui, Lisa, Martin, Lubitz, Steven A, Manichaikul, Ani W, Michael, Preuss, Montasser, May E, Morrison, Alanna C, Naseri, Take, O'Connell, Jeffrey R, Palmer, Nicholette D, Peyser, Patricia A, Reupena, Muagututia S, Smith, Jennifer A, Sun, Xiao, Taylor, Kent D, Tracy, Russell P, Tsai, Michael Y, Wang, Zhe, Wang, Yuxuan, Bao, Wei, Wilkins, John T, Yanek, Lisa R, Zhao, Wei, Arnett, Donna K, Blangero, John, Boerwinkle, Eric, Bowden, Donald W, Chen, Yii-Der Ida, Correa, Adolfo, Cupples, L Adrienne, Dutcher, Susan K, Ellinor, Patrick T, Fornage, Myriam, Gabriel, Stacey, Germer, Soren, Gibbs, Richard, He, Jiang, Kaplan, Robert C, Kardia, Sharon LR, Kim, Ryan, Kooperberg, Charles, Loos, Ruth JF, Viaud-Martinez, Karine A, Mathias, Rasika A, McGarvey, Stephen T, Mitchell, Braxton D, Nickerson, Deborah, North, Kari E, Psaty, Bruce M, Redline, Susan, Reiner, Alexander P, Vasan, Ramachandran S, Rich, Stephen S, Willer, Cristen, Rotter, Jerome I, Rader, Daniel J, Lin, Xihong, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Peloso, Gina M, and Natarajan, Pradeep
Abstract: Blood lipids are heritable modifiable causal factors for coronary artery disease. Despite well-described monogenic and polygenic bases of dyslipidemia, limitations remain in discovery of lipid-associated alleles using whole genome sequencing (WGS), partly due to limited sample sizes, ancestral diversity, and interpretation of clinical significance. Among 66,329 ancestrally diverse (56% non-European) participants, we associate 428M variants from deep-coverage WGS with lipid levels; ~400M variants were not assessed in prior lipids genetic analyses. We find multiple lipid-related genes strongly associated with blood lipids through analysis of common and rare coding variants. We discover several associated rare non-coding variants, largely at Mendelian lipid genes. Notably, we observe rare LDLR intronic variants associated with markedly increased LDL-C, similar to rare LDLR exonic variants. In conclusion, we conducted a systematic whole genome scan for blood lipids expanding the alleles linked to lipids for multiple ancestries and characterize a clinically-relevant rare non-coding variant model for lipids.
Published: 2022

35. Insights From a Large-Scale Whole-Genome Sequencing Study of Systolic Blood Pressure, Diastolic Blood Pressure, and Hypertension.

Author: Kelly, Tanika, Kelly, Tanika, Sun, Xiao, He, Karen, Brown, Michael, Taliun, Sarah, Hellwege, Jacklyn, Irvin, Marguerite, Mi, Xuenan, Brody, Jennifer, Franceschini, Nora, Guo, Xiuqing, Hwang, Shih-Jen, de Vries, Paul, Gao, Yan, Moscati, Arden, Nadkarni, Girish, Yanek, Lisa, Elfassy, Tali, Smith, Jennifer, Chung, Ren-Hua, Beitelshees, Amber, Patki, Amit, Aslibekyan, Stella, Blobner, Brandon, Peralta, Juan, Assimes, Themistocles, Palmas, Walter, Liu, Chunyu, Bress, Adam, Huang, Zhijie, Becker, Lewis, Hwa, Chii-Min, OConnell, Jeffrey, Carlson, Jenna, Warren, Helen, Das, Sayantan, Giri, Ayush, Martin, Lisa, Craig Johnson, W, Fox, Ervin, Bottinger, Erwin, Razavi, Alexander, Vaidya, Dhananjay, Chuang, Lee-Ming, Chang, Yen-Pei, Naseri, Take, Jain, Deepti, Kang, Hyun, Hung, Adriana, Srinivasasainagendra, Vinodh, Snively, Beverly, Gu, Dongfeng, Montasser, May, Reupena, Muagututia, Heavner, Benjamin, LeFaive, Jonathon, Hixson, James, Rice, Kenneth, Wang, Fei, Nielsen, Jonas, Huang, Jianfeng, Khan, Alyna, Zhou, Wei, Nierenberg, Jovia, Laurie, Cathy, Armstrong, Nicole, Shi, Mengyao, Pan, Yang, Stilp, Adrienne, Emery, Leslie, Wong, Quenna, Hawley, Nicola, Minster, Ryan, Curran, Joanne, Munroe, Patricia, Weeks, Daniel, North, Kari, Tracy, Russell, Kenny, Eimear, Shimbo, Daichi, Chakravarti, Aravinda, Rich, Stephen, Reiner, Alex, Blangero, John, Redline, Susan, Mitchell, Braxton, Rao, Dabeeru, Ida Chen, Yii-Der, Kardia, Sharon, Kaplan, Robert, Mathias, Rasika, He, Jiang, Psaty, Bruce, Fornage, Myriam, Loos, Ruth, Correa, Adolfo, Boerwinkle, Eric, Kooperberg, Charles, Edwards, Todd, Kelly, Tanika, Kelly, Tanika, Sun, Xiao, He, Karen, Brown, Michael, Taliun, Sarah, Hellwege, Jacklyn, Irvin, Marguerite, Mi, Xuenan, Brody, Jennifer, Franceschini, Nora, Guo, Xiuqing, Hwang, Shih-Jen, de Vries, Paul, Gao, Yan, Moscati, Arden, Nadkarni, Girish, Yanek, Lisa, Elfassy, Tali, Smith, Jennifer, Chung, Ren-Hua, Beitelshees, Amber, Patki, Amit, Aslibekyan, Stella, Blobner, Brandon, Peralta, Juan, Assimes, Themistocles, Palmas, Walter, Liu, Chunyu, Bress, Adam, Huang, Zhijie, Becker, Lewis, Hwa, Chii-Min, OConnell, Jeffrey, Carlson, Jenna, Warren, Helen, Das, Sayantan, Giri, Ayush, Martin, Lisa, Craig Johnson, W, Fox, Ervin, Bottinger, Erwin, Razavi, Alexander, Vaidya, Dhananjay, Chuang, Lee-Ming, Chang, Yen-Pei, Naseri, Take, Jain, Deepti, Kang, Hyun, Hung, Adriana, Srinivasasainagendra, Vinodh, Snively, Beverly, Gu, Dongfeng, Montasser, May, Reupena, Muagututia, Heavner, Benjamin, LeFaive, Jonathon, Hixson, James, Rice, Kenneth, Wang, Fei, Nielsen, Jonas, Huang, Jianfeng, Khan, Alyna, Zhou, Wei, Nierenberg, Jovia, Laurie, Cathy, Armstrong, Nicole, Shi, Mengyao, Pan, Yang, Stilp, Adrienne, Emery, Leslie, Wong, Quenna, Hawley, Nicola, Minster, Ryan, Curran, Joanne, Munroe, Patricia, Weeks, Daniel, North, Kari, Tracy, Russell, Kenny, Eimear, Shimbo, Daichi, Chakravarti, Aravinda, Rich, Stephen, Reiner, Alex, Blangero, John, Redline, Susan, Mitchell, Braxton, Rao, Dabeeru, Ida Chen, Yii-Der, Kardia, Sharon, Kaplan, Robert, Mathias, Rasika, He, Jiang, Psaty, Bruce, Fornage, Myriam, Loos, Ruth, Correa, Adolfo, Boerwinkle, Eric, Kooperberg, Charles, and Edwards, Todd
Abstract: BACKGROUND: The availability of whole-genome sequencing data in large studies has enabled the assessment of coding and noncoding variants across the allele frequency spectrum for their associations with blood pressure. METHODS: We conducted a multiancestry whole-genome sequencing analysis of blood pressure among 51 456 Trans-Omics for Precision Medicine and Centers for Common Disease Genomics program participants (stage-1). Stage-2 analyses leveraged array data from UK Biobank (N=383 145), Million Veteran Program (N=318 891), and Reasons for Geographic and Racial Differences in Stroke (N=10 643) participants, along with whole-exome sequencing data from UK Biobank (N=199 631) participants. RESULTS: Two blood pressure signals achieved genome-wide significance in meta-analyses of stage-1 and stage-2 single variant findings (P<5×10-8). Among them, a rare intergenic variant at novel locus, LOC100506274, was associated with lower systolic blood pressure in stage-1 (beta [SE]=-32.6 [6.0]; P=4.99×10-8) but not stage-2 analysis (P=0.11). Furthermore, a novel common variant at the known INSR locus was suggestively associated with diastolic blood pressure in stage-1 (beta [SE]=-0.36 [0.07]; P=4.18×10-7) and attained genome-wide significance in stage-2 (beta [SE]=-0.29 [0.03]; P=7.28×10-23). Nineteen additional signals suggestively associated with blood pressure in meta-analysis of single and aggregate rare variant findings (P<1×10-6 and P<1×10-4, respectively). DISCUSSION: We report one promising but unconfirmed rare variant for blood pressure and, more importantly, contribute insights for future blood pressure sequencing studies. Our findings suggest promise of aggregate analyses to complement single variant analysis strategies and the need for larger, diverse samples, and family studies to enable robust rare variant identification.
Published: 2022

36. Rare coding variants in RCN3 are associated with blood pressure.

Author: He, Karen Y, He, Karen Y, Kelly, Tanika N, Wang, Heming, Liang, Jingjing, Zhu, Luke, Cade, Brian E, Assimes, Themistocles L, Becker, Lewis C, Beitelshees, Amber L, Bielak, Lawrence F, Bress, Adam P, Brody, Jennifer A, Chang, Yen-Pei Christy, Chang, Yi-Cheng, de Vries, Paul S, Duggirala, Ravindranath, Fox, Ervin R, Franceschini, Nora, Furniss, Anna L, Gao, Yan, Guo, Xiuqing, Haessler, Jeffrey, Hung, Yi-Jen, Hwang, Shih-Jen, Irvin, Marguerite Ryan, Kalyani, Rita R, Liu, Ching-Ti, Liu, Chunyu, Martin, Lisa Warsinger, Montasser, May E, Muntner, Paul M, Mwasongwe, Stanford, Naseri, Take, Palmas, Walter, Reupena, Muagututi'a Sefuiva, Rice, Kenneth M, Sheu, Wayne H-H, Shimbo, Daichi, Smith, Jennifer A, Snively, Beverly M, Yanek, Lisa R, Zhao, Wei, Blangero, John, Boerwinkle, Eric, Chen, Yii-Der Ida, Correa, Adolfo, Cupples, L Adrienne, Curran, Joanne E, Fornage, Myriam, He, Jiang, Hou, Lifang, Kaplan, Robert C, Kardia, Sharon LR, Kenny, Eimear E, Kooperberg, Charles, Lloyd-Jones, Donald, Loos, Ruth JF, Mathias, Rasika A, McGarvey, Stephen T, Mitchell, Braxton D, North, Kari E, Peyser, Patricia A, Psaty, Bruce M, Raffield, Laura M, Rao, DC, Redline, Susan, Reiner, Alex P, Rich, Stephen S, Rotter, Jerome I, Taylor, Kent D, Tracy, Russell, Vasan, Ramachandran S, Samoan Obesity, Lifestyle and Genetic Adaptations Study (OLaGA) Group, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Morrison, Alanna C, Levy, Daniel, Chakravarti, Aravinda, Arnett, Donna K, Zhu, Xiaofeng, He, Karen Y, He, Karen Y, Kelly, Tanika N, Wang, Heming, Liang, Jingjing, Zhu, Luke, Cade, Brian E, Assimes, Themistocles L, Becker, Lewis C, Beitelshees, Amber L, Bielak, Lawrence F, Bress, Adam P, Brody, Jennifer A, Chang, Yen-Pei Christy, Chang, Yi-Cheng, de Vries, Paul S, Duggirala, Ravindranath, Fox, Ervin R, Franceschini, Nora, Furniss, Anna L, Gao, Yan, Guo, Xiuqing, Haessler, Jeffrey, Hung, Yi-Jen, Hwang, Shih-Jen, Irvin, Marguerite Ryan, Kalyani, Rita R, Liu, Ching-Ti, Liu, Chunyu, Martin, Lisa Warsinger, Montasser, May E, Muntner, Paul M, Mwasongwe, Stanford, Naseri, Take, Palmas, Walter, Reupena, Muagututi'a Sefuiva, Rice, Kenneth M, Sheu, Wayne H-H, Shimbo, Daichi, Smith, Jennifer A, Snively, Beverly M, Yanek, Lisa R, Zhao, Wei, Blangero, John, Boerwinkle, Eric, Chen, Yii-Der Ida, Correa, Adolfo, Cupples, L Adrienne, Curran, Joanne E, Fornage, Myriam, He, Jiang, Hou, Lifang, Kaplan, Robert C, Kardia, Sharon LR, Kenny, Eimear E, Kooperberg, Charles, Lloyd-Jones, Donald, Loos, Ruth JF, Mathias, Rasika A, McGarvey, Stephen T, Mitchell, Braxton D, North, Kari E, Peyser, Patricia A, Psaty, Bruce M, Raffield, Laura M, Rao, DC, Redline, Susan, Reiner, Alex P, Rich, Stephen S, Rotter, Jerome I, Taylor, Kent D, Tracy, Russell, Vasan, Ramachandran S, Samoan Obesity, Lifestyle and Genetic Adaptations Study (OLaGA) Group, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Morrison, Alanna C, Levy, Daniel, Chakravarti, Aravinda, Arnett, Donna K, and Zhu, Xiaofeng
Abstract: BackgroundWhile large genome-wide association studies have identified nearly one thousand loci associated with variation in blood pressure, rare variant identification is still a challenge. In family-based cohorts, genome-wide linkage scans have been successful in identifying rare genetic variants for blood pressure. This study aims to identify low frequency and rare genetic variants within previously reported linkage regions on chromosomes 1 and 19 in African American families from the Trans-Omics for Precision Medicine (TOPMed) program. Genetic association analyses weighted by linkage evidence were completed with whole genome sequencing data within and across TOPMed ancestral groups consisting of 60,388 individuals of European, African, East Asian, Hispanic, and Samoan ancestries.ResultsAssociations of low frequency and rare variants in RCN3 and multiple other genes were observed for blood pressure traits in TOPMed samples. The association of low frequency and rare coding variants in RCN3 was further replicated in UK Biobank samples (N = 403,522), and reached genome-wide significance for diastolic blood pressure (p = 2.01 × 10- 7).ConclusionsLow frequency and rare variants in RCN3 contributes blood pressure variation. This study demonstrates that focusing association analyses in linkage regions greatly reduces multiple-testing burden and improves power to identify novel rare variants associated with blood pressure traits.
Published: 2022

37. Genetic diversity fuels gene discovery for tobacco and alcohol use.

Author: Saunders, Gretchen RB, Saunders, Gretchen RB, Wang, Xingyan, Chen, Fang, Jang, Seon-Kyeong, Liu, Mengzhen, Wang, Chen, Gao, Shuang, Jiang, Yu, Khunsriraksakul, Chachrit, Otto, Jacqueline M, Addison, Clifton, Akiyama, Masato, Albert, Christine M, Aliev, Fazil, Alonso, Alvaro, Arnett, Donna K, Ashley-Koch, Allison E, Ashrani, Aneel A, Barnes, Kathleen C, Barr, R Graham, Bartz, Traci M, Becker, Diane M, Bielak, Lawrence F, Benjamin, Emelia J, Bis, Joshua C, Bjornsdottir, Gyda, Blangero, John, Bleecker, Eugene R, Boardman, Jason D, Boerwinkle, Eric, Boomsma, Dorret I, Boorgula, Meher Preethi, Bowden, Donald W, Brody, Jennifer A, Cade, Brian E, Chasman, Daniel I, Chavan, Sameer, Chen, Yii-Der Ida, Chen, Zhengming, Cheng, Iona, Cho, Michael H, Choquet, Hélène, Cole, John W, Cornelis, Marilyn C, Cucca, Francesco, Curran, Joanne E, de Andrade, Mariza, Dick, Danielle M, Docherty, Anna R, Duggirala, Ravindranath, Eaton, Charles B, Ehringer, Marissa A, Esko, Tõnu, Faul, Jessica D, Fernandes Silva, Lilian, Fiorillo, Edoardo, Fornage, Myriam, Freedman, Barry I, Gabrielsen, Maiken E, Garrett, Melanie E, Gharib, Sina A, Gieger, Christian, Gillespie, Nathan, Glahn, David C, Gordon, Scott D, Gu, Charles C, Gu, Dongfeng, Gudbjartsson, Daniel F, Guo, Xiuqing, Haessler, Jeffrey, Hall, Michael E, Haller, Toomas, Harris, Kathleen Mullan, He, Jiang, Herd, Pamela, Hewitt, John K, Hickie, Ian, Hidalgo, Bertha, Hokanson, John E, Hopfer, Christian, Hottenga, JoukeJan, Hou, Lifang, Huang, Hongyan, Hung, Yi-Jen, Hunter, David J, Hveem, Kristian, Hwang, Shih-Jen, Hwu, Chii-Min, Iacono, William, Irvin, Marguerite R, Jee, Yon Ho, Johnson, Eric O, Joo, Yoonjung Y, Jorgenson, Eric, Justice, Anne E, Kamatani, Yoichiro, Kaplan, Robert C, Kaprio, Jaakko, Kardia, Sharon LR, Keller, Matthew C, Saunders, Gretchen RB, Saunders, Gretchen RB, Wang, Xingyan, Chen, Fang, Jang, Seon-Kyeong, Liu, Mengzhen, Wang, Chen, Gao, Shuang, Jiang, Yu, Khunsriraksakul, Chachrit, Otto, Jacqueline M, Addison, Clifton, Akiyama, Masato, Albert, Christine M, Aliev, Fazil, Alonso, Alvaro, Arnett, Donna K, Ashley-Koch, Allison E, Ashrani, Aneel A, Barnes, Kathleen C, Barr, R Graham, Bartz, Traci M, Becker, Diane M, Bielak, Lawrence F, Benjamin, Emelia J, Bis, Joshua C, Bjornsdottir, Gyda, Blangero, John, Bleecker, Eugene R, Boardman, Jason D, Boerwinkle, Eric, Boomsma, Dorret I, Boorgula, Meher Preethi, Bowden, Donald W, Brody, Jennifer A, Cade, Brian E, Chasman, Daniel I, Chavan, Sameer, Chen, Yii-Der Ida, Chen, Zhengming, Cheng, Iona, Cho, Michael H, Choquet, Hélène, Cole, John W, Cornelis, Marilyn C, Cucca, Francesco, Curran, Joanne E, de Andrade, Mariza, Dick, Danielle M, Docherty, Anna R, Duggirala, Ravindranath, Eaton, Charles B, Ehringer, Marissa A, Esko, Tõnu, Faul, Jessica D, Fernandes Silva, Lilian, Fiorillo, Edoardo, Fornage, Myriam, Freedman, Barry I, Gabrielsen, Maiken E, Garrett, Melanie E, Gharib, Sina A, Gieger, Christian, Gillespie, Nathan, Glahn, David C, Gordon, Scott D, Gu, Charles C, Gu, Dongfeng, Gudbjartsson, Daniel F, Guo, Xiuqing, Haessler, Jeffrey, Hall, Michael E, Haller, Toomas, Harris, Kathleen Mullan, He, Jiang, Herd, Pamela, Hewitt, John K, Hickie, Ian, Hidalgo, Bertha, Hokanson, John E, Hopfer, Christian, Hottenga, JoukeJan, Hou, Lifang, Huang, Hongyan, Hung, Yi-Jen, Hunter, David J, Hveem, Kristian, Hwang, Shih-Jen, Hwu, Chii-Min, Iacono, William, Irvin, Marguerite R, Jee, Yon Ho, Johnson, Eric O, Joo, Yoonjung Y, Jorgenson, Eric, Justice, Anne E, Kamatani, Yoichiro, Kaplan, Robert C, Kaprio, Jaakko, Kardia, Sharon LR, and Keller, Matthew C
Abstract: Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury1-4. These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries5. Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.
Published: 2022

38. Black and White Adults With CKD Hospitalized With Acute Kidney Injury: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

Author: Feldman, Harold, Feldman, Harold, Srivastava, Anand, Bhat, Zeenat, Saraf, Santosh, Chen, Teresa, He, Jiang, Estrella, Michelle, Go, Alan, Hsu, Chi-Yuan, Yang, Jingrong, Derebail, Vimal, Liu, Kathleen, Muiru, Anthony, Feldman, Harold, Feldman, Harold, Srivastava, Anand, Bhat, Zeenat, Saraf, Santosh, Chen, Teresa, He, Jiang, Estrella, Michelle, Go, Alan, Hsu, Chi-Yuan, Yang, Jingrong, Derebail, Vimal, Liu, Kathleen, and Muiru, Anthony
Abstract: RATIONALE & OBJECTIVE: Few studies have investigated racial disparities in acute kidney injury (AKI), in contrast to the extensive literature on racial differences in the risk of kidney failure. We sought to study potential differences in risk in the setting of chronic kidney disease (CKD). STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: We studied 2,720 self-identified Black or White participants with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study from July 1, 2013, to December 31, 2017. EXPOSURE: Self-reported race (Black vs White). OUTCOME: Hospitalized AKI (≥50% increase from nadir to peak serum creatinine). ANALYTICAL APPROACH: Cox regression models adjusting for demographics (age and sex), prehospitalization clinical risk factors (diabetes, blood pressure, cardiovascular disease, estimated glomerular filtration rate, proteinuria, receipt of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers), and socioeconomic status (insurance status and education level). In a subset of participants with genotype data, we adjusted for apolipoprotein L1 gene (APOL1) high-risk status and sickle cell trait. RESULTS: Black participants (n = 1,266) were younger but had a higher burden of prehospitalization clinical risk factors. The incidence rate of first AKI hospitalization among Black participants was 6.3 (95% CI, 5.5-7.2) per 100 person-years versus 5.3 (95% CI, 4.6-6.1) per 100 person-years among White participants. In an unadjusted Cox regression model, Black participants were at a modestly increased risk of incident AKI (HR, 1.22 [95% CI, 1.01-1.48]) compared with White participants. However, this risk was attenuated and no longer significant after adjusting for prehospitalization clinical risk factors (adjusted HR, 1.02 [95% CI, 0.83-1.25]). There were only 11 AKI hospitalizations among individuals with high-risk APOL1 risk status and 14 AKI hospitalizations among individuals with sickle cell tra
Published: 2022

39. Enhanced Catalytic Performance through in Situ Encapsulation of Ultrafine Ru Clusters within a High-Aluminum Zeolite

Author: Sub Inorganic Chemistry and Catalysis, Faculteit Betawetenschappen, Inorganic Chemistry and Catalysis, Yang, Jiangqian, He, Ying, He, Jiang, Liu, Yuanshuai, Geng, Huawei, Chen, Shaohua, Lin, Lu, Liu, Meng, Chen, Tiehong, Jiang, Qike, Weckhuysen, Bert M., Luo, Wenhao, Wu, Zhijie, Sub Inorganic Chemistry and Catalysis, Faculteit Betawetenschappen, Inorganic Chemistry and Catalysis, Yang, Jiangqian, He, Ying, He, Jiang, Liu, Yuanshuai, Geng, Huawei, Chen, Shaohua, Lin, Lu, Liu, Meng, Chen, Tiehong, Jiang, Qike, Weckhuysen, Bert M., Luo, Wenhao, and Wu, Zhijie
Published: 2022

40. A Localization Method of High Energy Transients for All-Sky Gamma-Ray Monitor

Author: Zhao, Yi, Xue, Wangchen, Xiong, Shaolin, Luo, Qi, Wang, Yuanhao, Liu, Jiacong, Yu, Heng, Zhao, Xiaoyun, Huang, Yue, Liao, Jinyuan, Sun, Jianchao, Li, Xiaobo, Yi, Qibin, Cai, Ce, Xiao, Shuo, Xie, Shenglun, Zheng, Chao, Zhang, Yanqiu, Wang, Chenwei, Tan, Wenjun, Guo, Zhiwei, Li, Chaoyang, An, Zhenghua, Chen, Gang, Du, Yanqi, Gao, Min, Gong, Ke, Guo, Dongya, He, Jiang, He, Jianjian, Li, Bing, Li, Gang, Li, Xinqiao, Liang, Jing, Liang, Xiaohua, Liu, Yaqing, Ma, Xiang, Qiao, Rui, Song, Liming, Song, Xinying, Sun, Xilei, Wang, Jin, Wang, Ping, Wen, Xiangyang, Wu, Hong, Xu, Yanbing, Yang, Sheng, Zhang, Dali, Zhang, Fan, Zhang, Hongmei, Zhang, Peng, Zhang, Shu, Zhang, Zhen, Zheng, Shijie, Zhang, Keke, Han, Xingbo, Wu, Haiyan, Hu, Tai, Geng, Hao, Lu, Gaopeng, Xu, Wei, Lyu, Fanchao, Zhang, Hongbo, Lu, Fangjun, Zhang, Shuangnan, Zhao, Yi, Xue, Wangchen, Xiong, Shaolin, Luo, Qi, Wang, Yuanhao, Liu, Jiacong, Yu, Heng, Zhao, Xiaoyun, Huang, Yue, Liao, Jinyuan, Sun, Jianchao, Li, Xiaobo, Yi, Qibin, Cai, Ce, Xiao, Shuo, Xie, Shenglun, Zheng, Chao, Zhang, Yanqiu, Wang, Chenwei, Tan, Wenjun, Guo, Zhiwei, Li, Chaoyang, An, Zhenghua, Chen, Gang, Du, Yanqi, Gao, Min, Gong, Ke, Guo, Dongya, He, Jiang, He, Jianjian, Li, Bing, Li, Gang, Li, Xinqiao, Liang, Jing, Liang, Xiaohua, Liu, Yaqing, Ma, Xiang, Qiao, Rui, Song, Liming, Song, Xinying, Sun, Xilei, Wang, Jin, Wang, Ping, Wen, Xiangyang, Wu, Hong, Xu, Yanbing, Yang, Sheng, Zhang, Dali, Zhang, Fan, Zhang, Hongmei, Zhang, Peng, Zhang, Shu, Zhang, Zhen, Zheng, Shijie, Zhang, Keke, Han, Xingbo, Wu, Haiyan, Hu, Tai, Geng, Hao, Lu, Gaopeng, Xu, Wei, Lyu, Fanchao, Zhang, Hongbo, Lu, Fangjun, and Zhang, Shuangnan
Abstract: Fast and reliable localization of high-energy transients is crucial for characterizing the burst properties and guiding the follow-up observations. Localization based on the relative counts of different detectors has been widely used for all-sky gamma-ray monitors. There are two major methods for this counts distribution localization: $\chi^{2}$ minimization method and the Bayesian method. Here we propose a modified Bayesian method that could take advantage of both the accuracy of the Bayesian method and the simplicity of the $\chi^{2}$ method. With comprehensive simulations, we find that our Bayesian method with Poisson likelihood is generally more applicable for various bursts than $\chi^{2}$ method, especially for weak bursts. We further proposed a location-spectrum iteration approach based on the Bayesian inference, which could alleviate the problems caused by the spectral difference between the burst and location templates. Our method is very suitable for scenarios with limited computation resources or time-sensitive applications, such as in-flight localization software, and low-latency localization for rapid follow-up observations.
Published: 2022

41. Synthetic Circuit-Driven Expression of Heterologous Enzymes for Disease Detection

Author: Koch Institute for Integrative Cancer Research at MIT, Harvard University--MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Howard Hughes Medical Institute, Massachusetts Institute of Technology. Research Laboratory of Electronics, Massachusetts Institute of Technology. Department of Biological Engineering, He, Jiang, Nissim, Lior, Soleimany, Ava P, Binder-Nissim, Adina, Fleming, Heather E, Lu, Timothy K, Bhatia, Sangeeta N, Koch Institute for Integrative Cancer Research at MIT, Harvard University--MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Howard Hughes Medical Institute, Massachusetts Institute of Technology. Research Laboratory of Electronics, Massachusetts Institute of Technology. Department of Biological Engineering, He, Jiang, Nissim, Lior, Soleimany, Ava P, Binder-Nissim, Adina, Fleming, Heather E, Lu, Timothy K, and Bhatia, Sangeeta N
Abstract: The integration of nanotechnology and synthetic biology could lay the framework for new classes of engineered biosensors that produce amplified readouts of disease states. As a proof-of-concept demonstration of this vision, here we present an engineered gene circuit that, in response to cancer-associated transcriptional deregulation, expresses heterologous enzyme biomarkers whose activity can be measured by nanoparticle sensors that generate amplified detection readouts. Specifically, we designed an AND-gate gene circuit that integrates the activity of two ovarian cancer-specific synthetic promoters to drive the expression of a heterologous protein output, secreted Tobacco Etch Virus (TEV) protease, exclusively from within tumor cells. Nanoparticle probes were engineered to carry a TEV-specific peptide substrate in order to measure the activity of the circuit-generated enzyme to yield amplified detection signals measurable in the urine or blood. We applied our integrated sense-and-respond system in a mouse model of disseminated ovarian cancer, where we demonstrated measurement of circuit-specific TEV protease activity both in vivo using exogenously administered nanoparticle sensors and ex vivo using quenched fluorescent probes. We envision that this work will lay the foundation for how synthetic biology and nanotechnology can be meaningfully integrated to achieve next-generation engineered biosensors.
Published: 2022

42. NTIRE 2022 Spectral Recovery Challenge and Data Set

Author: Arad, B, Timofte, R, Yahel, R, Morag, N, Bernat, A, Cai, Y, Lin, J, Lin, Z, Wang, H, Zhang, Y, Pfister, H, Van Gool, L, Liu, S, Li, Y, Feng, C, Lei, L, Li, J, Du, S, Wu, C, Leng, Y, Song, R, Zhang, M, Song, C, Zhao, S, Lang, Z, Wei, W, Zhang, L, Dian, R, Shan, T, Guo, A, Liu, J, Agarla, M, Bianco, S, Buzzelli, M, Celona, L, Schettini, R, He, J, Xiao, Y, Xiao, J, Yuan, Q, Kwon, T, Ryu, D, Bae, H, Yang, H, Chang, H, Huang, Z, Chen, W, Kuo, S, Chen, J, Li, H, Sabarinathan, S, Uma, K, Bama, B, Roomi, S, Arad, Boaz, Timofte, Radu, Yahel, Rony, Morag, Nimrod, Bernat, Amir, Cai, Yuanhao, Lin, Jing, Lin, Zudi, Wang, Haoqian, Zhang, Yulun, Pfister, Hanspeter, Van Gool, Luc, Liu, Shuai, Li, Yongqiang, Feng, Chaoyu, Lei, Lei, Li, Jiaojiao, Du, Songcheng, Wu, Chaoxiong, Leng, Yihong, Song, Rui, Zhang, Mingwei, Song, Chongxing, Zhao, Shuyi, Lang, Zhiqiang, Wei, Wei, Zhang, Lei, Dian, Renwei, Shan, Tianci, Guo, Anjing, Feng, Chengguo, Liu, Jinyang, Agarla, Mirko, Bianco, Simone, Buzzelli, Marco, Celona, Luigi, Schettini, Raimondo, He, Jiang, Xiao, Yi, Xiao, Jiajun, Yuan, Qiangqiang, Li, Jie, Zhang, Liangpei, Kwon, Taesung, Ryu, Dohoon, Bae, Hyokyoung, Yang, Hao-Hsiang, Chang, Hua-En, Huang, Zhi-Kai, Chen, Wei-Ting, Kuo, Sy-Yen, Chen, Junyu, Li, Haiwei, Liu, Song, Sabarinathan, Sabarinathan, Bama, B Sathya, Roomi, S. Mohamed Mansoor, Arad, B, Timofte, R, Yahel, R, Morag, N, Bernat, A, Cai, Y, Lin, J, Lin, Z, Wang, H, Zhang, Y, Pfister, H, Van Gool, L, Liu, S, Li, Y, Feng, C, Lei, L, Li, J, Du, S, Wu, C, Leng, Y, Song, R, Zhang, M, Song, C, Zhao, S, Lang, Z, Wei, W, Zhang, L, Dian, R, Shan, T, Guo, A, Liu, J, Agarla, M, Bianco, S, Buzzelli, M, Celona, L, Schettini, R, He, J, Xiao, Y, Xiao, J, Yuan, Q, Kwon, T, Ryu, D, Bae, H, Yang, H, Chang, H, Huang, Z, Chen, W, Kuo, S, Chen, J, Li, H, Sabarinathan, S, Uma, K, Bama, B, Roomi, S, Arad, Boaz, Timofte, Radu, Yahel, Rony, Morag, Nimrod, Bernat, Amir, Cai, Yuanhao, Lin, Jing, Lin, Zudi, Wang, Haoqian, Zhang, Yulun, Pfister, Hanspeter, Van Gool, Luc, Liu, Shuai, Li, Yongqiang, Feng, Chaoyu, Lei, Lei, Li, Jiaojiao, Du, Songcheng, Wu, Chaoxiong, Leng, Yihong, Song, Rui, Zhang, Mingwei, Song, Chongxing, Zhao, Shuyi, Lang, Zhiqiang, Wei, Wei, Zhang, Lei, Dian, Renwei, Shan, Tianci, Guo, Anjing, Feng, Chengguo, Liu, Jinyang, Agarla, Mirko, Bianco, Simone, Buzzelli, Marco, Celona, Luigi, Schettini, Raimondo, He, Jiang, Xiao, Yi, Xiao, Jiajun, Yuan, Qiangqiang, Li, Jie, Zhang, Liangpei, Kwon, Taesung, Ryu, Dohoon, Bae, Hyokyoung, Yang, Hao-Hsiang, Chang, Hua-En, Huang, Zhi-Kai, Chen, Wei-Ting, Kuo, Sy-Yen, Chen, Junyu, Li, Haiwei, Liu, Song, Sabarinathan, Sabarinathan, Bama, B Sathya, and Roomi, S. Mohamed Mansoor
Abstract: This paper reviews the third biennial challenge on spectral reconstruction from RGB images, i.e., the recovery of whole-scene hyperspectral (HS) information from a 3-channel RGB image. This challenge presents the "ARAD_1K"data set: a new, larger-than-ever natural hyperspectral image data set containing 1,000 images. Challenge participants were required to recover hyper-spectral information from synthetically generated JPEG-compressed RGB images simulating capture by a known calibrated camera, operating under partially known parameters, in a setting which includes acquisition noise. The challenge was attended by 241 teams, with 60 teams com-peting in the final testing phase, 12 of which provided de-tailed descriptions of their methodology which are included in this report. The performance of these submissions is re-viewed and provided here as a gauge for the current state-of-the-art in spectral reconstruction from natural RGB images.
Published: 2022

43. Genomic Alteration Spectrum of Non-Small Cell Lung Cancer Patients in East-China Characterized by Tumor Tissue DNA and Cell-Free DNA

Author: Li,Jie, Chen,Siwen, Xue,Hui, Wang,Haoyi, Huang,Tianwei, Xie,Hongya, He,Jiang, Ke,Cai, Yu,Zhaonan, Ni,Bin, Li,Jie, Chen,Siwen, Xue,Hui, Wang,Haoyi, Huang,Tianwei, Xie,Hongya, He,Jiang, Ke,Cai, Yu,Zhaonan, and Ni,Bin
Abstract: Jie Li,1,&ast; Siwen Chen,1,&ast; Hui Xue,2,&ast; Haoyi Wang,3,&ast; Tianwei Huang,4 Hongya Xie,5 Jiang He,6 Cai Ke,3 Zhaonan Yu,3 Bin Ni4 1Department of General Medical Ward, First Affiliated Hospital of Soochow University, Suzhou, Peopleâs Republic of China; 2Department of Oncology Medical Ward, Hanzhong Central Hospital, Hanzhong, Peopleâs Republic of China; 3Hangzhou D.A. Medical Laboratory, Hangzhou, Peopleâs Republic of China; 4Department of Thoracic Surgery, First Affiliated Hospital of Soochow University, Suzhou, Peopleâs Republic of China; 5Department of Thoracic Surgery, Suzhou Municipal Hospital, Suzhou, Peopleâs Republic of China; 6Department of Thoracic Surgery, Suzhou Wuzhong Peopleâs Hospital, Suzhou, Peopleâs Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Ni, Department of Thoracic Surgery, First Affiliated Hospital of Soochow University, Suzhou, Peopleâs Republic of China, Tel +86 17774015977, Email bin_ni@163.com Zhaonan Yu, Hangzhou D.A. Medical Laboratory, Hangzhou, Peopleâs Republic of China, Tel +86 15558078770, Email yuzhaonan870213@163.comIntroduction: From an oncologic perspective, genetic detection is becoming a frontline clinical test, used to identify actionable alterations for targeted therapy, monitor molecular clonal tumor evolution, indicate disease progression and prognosis, and predict medication efficacy and resistance. From analysis of both tumor tissue and cell-free DNA from a large cohort of non-small cell lung cancer patients in East-China, we characterized the full spectrum of genomic alterations.Methods: The study comprised 3000 unpaired samples including 1351 tumor tissue DNA (tDNA) and 1649 cell-free circulating tumor DNA (cfDNA) samples, from which 67 cancer-related genes were sequenced and the genetic alteration profiles were depicted. Integrative molecular analyses identified the frequently mutated genes, uncovered co-occurring somatic alterat
Published: 2022

44. Quantitative 99mTc Labeling Kit for HYNIC-Conjugated Single Chain Antibody Fragments Targeting Malignant Mesothelioma

Author: He, Jiang, He, Jiang, Feng, Jinjin, Su, Yang, Seo, Youngho, Liu, Bin, He, Jiang, He, Jiang, Feng, Jinjin, Su, Yang, Seo, Youngho, and Liu, Bin
Published: 2020

45. Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants

Author: Zhou, Bin Carrillo-Larco, Rodrigo M. Danaei, Goodarz Riley, Leanne M. Paciorek, Christopher J. Stevens, Gretchen A. and Gregg, Edward W. Bennett, James E. Solomon, Bethlehem and Singleton, Rosie K. Sophiea, Marisa K. Iurilli, Maria L. C. and Lhoste, Victor P. F. Cowan, Melanie J. Savin, Stefan and Woodward, Mark Balanova, Yulia Cifkova, Renata Damasceno, Albertino Elliott, Paul Farzadfar, Farshad He, Jiang and Ikeda, Nayu Kengne, Andre P. Khang, Young-Ho Kim, Hyeon Chang Laxmaiah, Avula Lin, Hsien-Ho Margozzini Maira, Paula and Miranda, J. Jaime Neuhauser, Hannelore Sundstrom, Johan and Varghese, Cherian Widyahening, Indah S. Zdrojewski, Tomasz and Ezzati, Majid Abarca-Gomez, Leandra Abdeen, Ziad A. Rahim, Hanan F. Abdul Abu-Rmeileh, Niveen M. Acosta-Cazares, Benjamin and Adams, Robert J. Aekplakorn, Wichai Afsana, Kaosar and Afzal, Shoaib Agdeppa, Imelda A. Aghazadeh-Attari, Javad and Aguilar-Salinas, Carlos A. Agyemang, Charles Ahmad, Noor Ani and Ahmadi, Ali Ahmadi, Naser Ahmadi, Nastaran Ahmadizar, Fariba and Ahmed, Soheir H. Ahrens, Wolfgang Ajlouni, Kamel and Al-Raddadi, Rajaa Alarouj, Monira AlBuhairan, Fadia and AlDhukair, Shahla Ali, Mohamed M. Alkandari, Abdullah and Alkerwi, Ala'a Allin, Kristine Aly, Eman Amarapurkar, Deepak N. Amougou, Norbert Amouyel, Philippe Andersen, Lars Bo and Anderssen, Sigmund A. Anjana, Ranjit Mohan Ansari-Moghaddam, Alireza Ansong, Daniel Aounallah-Skhiri, Hajer Araujo, Joana and Ariansen, Inger Aris, Tahir Arku, Raphael E. Arlappa, Nimmathota Aryal, Krishna K. Aspelund, Thor Assah, Felix K. and Assuncao, Maria Cecilia F. Auvinen, Juha Avdicova, Maria and Azevedo, Ana Azimi-Nezhad, Mohsen Azizi, Fereidoun Azmin, Mehrdad Babu, Bontha V. Bahijri, Suhad Balakrishna, Nagalla and Balanova, Yulia Bamoshmoosh, Mohamed Banach, Maciej and Banadinovic, Maja Bandosz, Piotr Banegas, Jose R. Baran, Joanna Barbagallo, Carlo M. Barcelo, Alberto Barkat, Amina and Barreto, Marta Barros, Aluisio J. D. Gomes Barros, Mauro Virgilio Bartosiew and Zhou, Bin Carrillo-Larco, Rodrigo M. Danaei, Goodarz Riley, Leanne M. Paciorek, Christopher J. Stevens, Gretchen A. and Gregg, Edward W. Bennett, James E. Solomon, Bethlehem and Singleton, Rosie K. Sophiea, Marisa K. Iurilli, Maria L. C. and Lhoste, Victor P. F. Cowan, Melanie J. Savin, Stefan and Woodward, Mark Balanova, Yulia Cifkova, Renata Damasceno, Albertino Elliott, Paul Farzadfar, Farshad He, Jiang and Ikeda, Nayu Kengne, Andre P. Khang, Young-Ho Kim, Hyeon Chang Laxmaiah, Avula Lin, Hsien-Ho Margozzini Maira, Paula and Miranda, J. Jaime Neuhauser, Hannelore Sundstrom, Johan and Varghese, Cherian Widyahening, Indah S. Zdrojewski, Tomasz and Ezzati, Majid Abarca-Gomez, Leandra Abdeen, Ziad A. Rahim, Hanan F. Abdul Abu-Rmeileh, Niveen M. Acosta-Cazares, Benjamin and Adams, Robert J. Aekplakorn, Wichai Afsana, Kaosar and Afzal, Shoaib Agdeppa, Imelda A. Aghazadeh-Attari, Javad and Aguilar-Salinas, Carlos A. Agyemang, Charles Ahmad, Noor Ani and Ahmadi, Ali Ahmadi, Naser Ahmadi, Nastaran Ahmadizar, Fariba and Ahmed, Soheir H. Ahrens, Wolfgang Ajlouni, Kamel and Al-Raddadi, Rajaa Alarouj, Monira AlBuhairan, Fadia and AlDhukair, Shahla Ali, Mohamed M. Alkandari, Abdullah and Alkerwi, Ala'a Allin, Kristine Aly, Eman Amarapurkar, Deepak N. Amougou, Norbert Amouyel, Philippe Andersen, Lars Bo and Anderssen, Sigmund A. Anjana, Ranjit Mohan Ansari-Moghaddam, Alireza Ansong, Daniel Aounallah-Skhiri, Hajer Araujo, Joana and Ariansen, Inger Aris, Tahir Arku, Raphael E. Arlappa, Nimmathota Aryal, Krishna K. Aspelund, Thor Assah, Felix K. and Assuncao, Maria Cecilia F. Auvinen, Juha Avdicova, Maria and Azevedo, Ana Azimi-Nezhad, Mohsen Azizi, Fereidoun Azmin, Mehrdad Babu, Bontha V. Bahijri, Suhad Balakrishna, Nagalla and Balanova, Yulia Bamoshmoosh, Mohamed Banach, Maciej and Banadinovic, Maja Bandosz, Piotr Banegas, Jose R. Baran, Joanna Barbagallo, Carlo M. Barcelo, Alberto Barkat, Amina and Barreto, Marta Barros, Aluisio J. D. Gomes Barros, Mauro Virgilio Bartosiew
Abstract: Background Hypertension can be detected at the primary health-care level and low-cost treatments can effectively control hypertension. We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories. Methods We used data from 1990 to 2019 on people aged 30-79 years from population-representative studies with measurement of blood pressure and data on blood pressure treatment. We defined hypertension as having systolic blood pressure 140 mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or taking medication for hypertension. We applied a Bayesian hierarchical model to estimate the prevalence of hypertension and the proportion of people with hypertension who had a previous diagnosis (detection), who were taking medication for hypertension (treatment), and whose hypertension was controlled to below 140/90 mm Hg (control). The model allowed for trends over time to be non-linear and to vary by age. Findings The number of people aged 30-79 years with hypertension doubled from 1990 to 2019, from 331 (95% credible interval 306-359) million women and 317 (292-344) million men in 1990 to 626 (584-668) million women and 652 (604-698) million men in 2019, despite stable global age-standardised prevalence. In 2019, age-standardised hypertension prevalence was lowest in Canada and Peru for both men and women; in Taiwan, South Korea, Japan, and some countries in western Europe including Switzerland, Spain, and the UK for women; and in several low-income and middle-income countries such as Eritrea, Bangladesh, Ethiopia, and Solomon Islands for men. Hypertension prevalence surpassed 50% for women in two countries and men in nine countries, in central and eastern Europe, central Asia, Oceania, and Latin America. Globally, 59% (55-62) of women and 49% (46-52) of men with hypertension reported a previous diagnosis of hypertension in 2019, and 47% (43-51) of women and 38% (35-41) of
Published: 2021

46. Zeolite-Tailored Active Site Proximity for the Efficient Production of Pentanoic Biofuels

Author: He, Jiang, Wu, Zhijie, Gu, Qingqing, Liu, Yuanshuai, Chu, Shenqi, Chen, Shaohua, Zhang, Yafeng, Yang, Bing, Chen, Tiehong, Wang, Aiqin, Weckhuysen, Bert M, Zhang, Tao, Luo, Wenhao, He, Jiang, Wu, Zhijie, Gu, Qingqing, Liu, Yuanshuai, Chu, Shenqi, Chen, Shaohua, Zhang, Yafeng, Yang, Bing, Chen, Tiehong, Wang, Aiqin, Weckhuysen, Bert M, Zhang, Tao, and Luo, Wenhao
Abstract: Biofuel production can alleviate reliance on fossil resources and thus carbon dioxide emission. Hydrodeoxygenation (HDO) refers collectively to a series of important biorefinery processes to produce biofuels. Here, well-dispersed and ultra-small Ru metal nanoclusters (ca. 1 nm), confined within the micropores of zeolite Y, provide the required active site intimacy, which significantly boosts the chemoselectivity towards the production of pentanoic biofuels in the direct, one-pot HDO of neat ethyl levulinate. Crucial for improving catalyst stability is the addition of La, which upholds the confined proximity by preventing zeolite lattice deconstruction during catalysis. We have established and extended an understanding of the “intimacy criterion” in catalytic biomass valorization. These findings bring new understanding of HDO reactions over confined proximity sites, leading to potential application for pentanoic biofuels in biomass conversion.
Published: 2021

47. Atrial Fibrillation and Longitudinal Change in Cognitive Function in CKD.

Author: McCauley, Mark D, McCauley, Mark D, Hsu, Jesse Y, Ricardo, Ana C, Darbar, Dawood, Kansal, Mayank, Kurella Tamura, Manjula, Feldman, Harold I, Kusek, John W, Taliercio, Jonathan J, Rao, Panduranga S, Shafi, Tariq, He, Jiang, Wang, Xue, Sha, Daohang, Lamar, Melissa, Go, Alan S, Yaffe, Kristine, Lash, James P, CRIC Study Investigators, McCauley, Mark D, McCauley, Mark D, Hsu, Jesse Y, Ricardo, Ana C, Darbar, Dawood, Kansal, Mayank, Kurella Tamura, Manjula, Feldman, Harold I, Kusek, John W, Taliercio, Jonathan J, Rao, Panduranga S, Shafi, Tariq, He, Jiang, Wang, Xue, Sha, Daohang, Lamar, Melissa, Go, Alan S, Yaffe, Kristine, Lash, James P, and CRIC Study Investigators
Abstract: BackgroundStudies in the general population suggest that atrial fibrillation (AF) is an independent risk factor for decline in cognitive function, but this relationship has not been examined in adults with chronic kidney disease (CKD). We investigated the association between incident AF and changes in cognitive function over time in this population.Methods and resultsWe studied a subgroup of 3254 adults participating in the Chronic Renal Insufficiency Cohort Study. Incident AF was ascertained by 12-lead electrocardiogram (ECG) obtained at a study visit and/or identification of a hospitalization with AF during follow-up. Cognitive function was assessed biennially using the Modified Mini-Mental State Exam. Linear mixed effects regression was used to evaluate the association between incident AF and longitudinal change in cognitive function. Compared with individuals without incident AF (n = 3158), those with incident AF (n = 96) were older, had a higher prevalence of cardiovascular disease and hypertension, and lower estimated glomerular filtration rate. After median follow-up of 6.8 years, we observed no significant multivariable association between incident AF and change in cognitive function test score.ConclusionIn this cohort of adults with CKD, incident AF was not associated with a decline in cognitive function.
Published: 2021

48. Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices.

Author: Natarajan, Pradeep, Natarajan, Pradeep, Pampana, Akhil, Graham, Sarah E, Ruotsalainen, Sanni E, Perry, James A, de Vries, Paul S, Broome, Jai G, Pirruccello, James P, Honigberg, Michael C, Aragam, Krishna, Wolford, Brooke, Brody, Jennifer A, Antonacci-Fulton, Lucinda, Arden, Moscati, Aslibekyan, Stella, Assimes, Themistocles L, Ballantyne, Christie M, Bielak, Lawrence F, Bis, Joshua C, Cade, Brian E, Do, Ron, Doddapaneni, Harsha, Emery, Leslie S, Hung, Yi-Jen, Irvin, Marguerite R, Khan, Alyna T, Lange, Leslie, Lee, Jiwon, Lemaitre, Rozenn N, Martin, Lisa W, Metcalf, Ginger, Montasser, May E, Moon, Jee-Young, Muzny, Donna, O'Connell, Jeffrey R, Palmer, Nicholette D, Peralta, Juan M, Peyser, Patricia A, Stilp, Adrienne M, Tsai, Michael, Wang, Fei Fei, Weeks, Daniel E, Yanek, Lisa R, Wilson, James G, Abecasis, Goncalo, Arnett, Donna K, Becker, Lewis C, Blangero, John, Boerwinkle, Eric, Bowden, Donald W, Chang, Yi-Cheng, Chen, Yii-Der I, Choi, Won Jung, Correa, Adolfo, Curran, Joanne E, Daly, Mark J, Dutcher, Susan K, Ellinor, Patrick T, Fornage, Myriam, Freedman, Barry I, Gabriel, Stacey, Germer, Soren, Gibbs, Richard A, He, Jiang, Hveem, Kristian, Jarvik, Gail P, Kaplan, Robert C, Kardia, Sharon LR, Kenny, Eimear, Kim, Ryan W, Kooperberg, Charles, Laurie, Cathy C, Lee, Seonwook, Lloyd-Jones, Don M, Loos, Ruth JF, Lubitz, Steven A, Mathias, Rasika A, Martinez, Karine A Viaud, McGarvey, Stephen T, Mitchell, Braxton D, Nickerson, Deborah A, North, Kari E, Palotie, Aarno, Park, Cheol Joo, Psaty, Bruce M, Rao, DC, Redline, Susan, Reiner, Alexander P, Seo, Daekwan, Seo, Jeong-Sun, Smith, Albert V, Tracy, Russell P, Vasan, Ramachandran S, Kathiresan, Sekar, Cupples, L Adrienne, Rotter, Jerome I, Morrison, Alanna C, Rich, Stephen S, Ripatti, Samuli, Willer, Cristen, Natarajan, Pradeep, Natarajan, Pradeep, Pampana, Akhil, Graham, Sarah E, Ruotsalainen, Sanni E, Perry, James A, de Vries, Paul S, Broome, Jai G, Pirruccello, James P, Honigberg, Michael C, Aragam, Krishna, Wolford, Brooke, Brody, Jennifer A, Antonacci-Fulton, Lucinda, Arden, Moscati, Aslibekyan, Stella, Assimes, Themistocles L, Ballantyne, Christie M, Bielak, Lawrence F, Bis, Joshua C, Cade, Brian E, Do, Ron, Doddapaneni, Harsha, Emery, Leslie S, Hung, Yi-Jen, Irvin, Marguerite R, Khan, Alyna T, Lange, Leslie, Lee, Jiwon, Lemaitre, Rozenn N, Martin, Lisa W, Metcalf, Ginger, Montasser, May E, Moon, Jee-Young, Muzny, Donna, O'Connell, Jeffrey R, Palmer, Nicholette D, Peralta, Juan M, Peyser, Patricia A, Stilp, Adrienne M, Tsai, Michael, Wang, Fei Fei, Weeks, Daniel E, Yanek, Lisa R, Wilson, James G, Abecasis, Goncalo, Arnett, Donna K, Becker, Lewis C, Blangero, John, Boerwinkle, Eric, Bowden, Donald W, Chang, Yi-Cheng, Chen, Yii-Der I, Choi, Won Jung, Correa, Adolfo, Curran, Joanne E, Daly, Mark J, Dutcher, Susan K, Ellinor, Patrick T, Fornage, Myriam, Freedman, Barry I, Gabriel, Stacey, Germer, Soren, Gibbs, Richard A, He, Jiang, Hveem, Kristian, Jarvik, Gail P, Kaplan, Robert C, Kardia, Sharon LR, Kenny, Eimear, Kim, Ryan W, Kooperberg, Charles, Laurie, Cathy C, Lee, Seonwook, Lloyd-Jones, Don M, Loos, Ruth JF, Lubitz, Steven A, Mathias, Rasika A, Martinez, Karine A Viaud, McGarvey, Stephen T, Mitchell, Braxton D, Nickerson, Deborah A, North, Kari E, Palotie, Aarno, Park, Cheol Joo, Psaty, Bruce M, Rao, DC, Redline, Susan, Reiner, Alexander P, Seo, Daekwan, Seo, Jeong-Sun, Smith, Albert V, Tracy, Russell P, Vasan, Ramachandran S, Kathiresan, Sekar, Cupples, L Adrienne, Rotter, Jerome I, Morrison, Alanna C, Rich, Stephen S, Ripatti, Samuli, and Willer, Cristen
Abstract: Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10-72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10-4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10-5). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids.
Published: 2021

49. Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci.

Author: de Las Fuentes, Lisa, de Las Fuentes, Lisa, Sung, Yun Ju, Noordam, Raymond, Winkler, Thomas, Feitosa, Mary F, Schwander, Karen, Bentley, Amy R, Brown, Michael R, Guo, Xiuqing, Manning, Alisa, Chasman, Daniel I, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Campbell, Archie, Cheng, Ching-Yu, Dorajoo, Rajkumar, Hartwig, Fernando P, Horimoto, ARVR, Li, Changwei, Li-Gao, Ruifang, Liu, Yongmei, Marten, Jonathan, Musani, Solomon K, Ntalla, Ioanna, Rankinen, Tuomo, Richard, Melissa, Sim, Xueling, Smith, Albert V, Tajuddin, Salman M, Tayo, Bamidele O, Vojinovic, Dina, Warren, Helen R, Xuan, Deng, Alver, Maris, Boissel, Mathilde, Chai, Jin-Fang, Chen, Xu, Christensen, Kaare, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Girotto, Giorgia, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Kühnel, Brigitte, Laguzzi, Federica, Li, Xiaoyin, Lyytikäinen, Leo-Pekka, Nolte, Ilja M, Poveda, Alaitz, Rauramaa, Rainer, Riaz, Muhammad, Rueedi, Rico, Shu, Xiao-Ou, Snieder, Harold, Sofer, Tamar, Takeuchi, Fumihiko, Verweij, Niek, Ware, Erin B, Weiss, Stefan, Yanek, Lisa R, Amin, Najaf, Arking, Dan E, Arnett, Donna K, Bergmann, Sven, Boerwinkle, Eric, Brody, Jennifer A, Broeckel, Ulrich, Brumat, Marco, Burke, Gregory, Cabrera, Claudia P, Canouil, Mickaël, Chee, Miao Li, Chen, Yii-Der Ida, Cocca, Massimiliano, Connell, John, de Silva, H Janaka, de Vries, Paul S, Eiriksdottir, Gudny, Faul, Jessica D, Fisher, Virginia, Forrester, Terrence, Fox, Ervin F, Friedlander, Yechiel, Gao, He, Gigante, Bruna, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B, He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven, Ikram, M Arfan, Irvin, Marguerite R, Kähönen, Mika, Kavousi, Maryam, de Las Fuentes, Lisa, de Las Fuentes, Lisa, Sung, Yun Ju, Noordam, Raymond, Winkler, Thomas, Feitosa, Mary F, Schwander, Karen, Bentley, Amy R, Brown, Michael R, Guo, Xiuqing, Manning, Alisa, Chasman, Daniel I, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Campbell, Archie, Cheng, Ching-Yu, Dorajoo, Rajkumar, Hartwig, Fernando P, Horimoto, ARVR, Li, Changwei, Li-Gao, Ruifang, Liu, Yongmei, Marten, Jonathan, Musani, Solomon K, Ntalla, Ioanna, Rankinen, Tuomo, Richard, Melissa, Sim, Xueling, Smith, Albert V, Tajuddin, Salman M, Tayo, Bamidele O, Vojinovic, Dina, Warren, Helen R, Xuan, Deng, Alver, Maris, Boissel, Mathilde, Chai, Jin-Fang, Chen, Xu, Christensen, Kaare, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Girotto, Giorgia, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Kühnel, Brigitte, Laguzzi, Federica, Li, Xiaoyin, Lyytikäinen, Leo-Pekka, Nolte, Ilja M, Poveda, Alaitz, Rauramaa, Rainer, Riaz, Muhammad, Rueedi, Rico, Shu, Xiao-Ou, Snieder, Harold, Sofer, Tamar, Takeuchi, Fumihiko, Verweij, Niek, Ware, Erin B, Weiss, Stefan, Yanek, Lisa R, Amin, Najaf, Arking, Dan E, Arnett, Donna K, Bergmann, Sven, Boerwinkle, Eric, Brody, Jennifer A, Broeckel, Ulrich, Brumat, Marco, Burke, Gregory, Cabrera, Claudia P, Canouil, Mickaël, Chee, Miao Li, Chen, Yii-Der Ida, Cocca, Massimiliano, Connell, John, de Silva, H Janaka, de Vries, Paul S, Eiriksdottir, Gudny, Faul, Jessica D, Fisher, Virginia, Forrester, Terrence, Fox, Ervin F, Friedlander, Yechiel, Gao, He, Gigante, Bruna, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B, He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven, Ikram, M Arfan, Irvin, Marguerite R, Kähönen, Mika, and Kavousi, Maryam
Abstract: Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
Published: 2021

50. Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci.

Author: de Las Fuentes, Lisa, de Las Fuentes, Lisa, Sung, Yun Ju, Noordam, Raymond, Winkler, Thomas, Feitosa, Mary F, Schwander, Karen, Bentley, Amy R, Brown, Michael R, Guo, Xiuqing, Manning, Alisa, Chasman, Daniel I, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Campbell, Archie, Cheng, Ching-Yu, Dorajoo, Rajkumar, Hartwig, Fernando P, Horimoto, ARVR, Li, Changwei, Li-Gao, Ruifang, Liu, Yongmei, Marten, Jonathan, Musani, Solomon K, Ntalla, Ioanna, Rankinen, Tuomo, Richard, Melissa, Sim, Xueling, Smith, Albert V, Tajuddin, Salman M, Tayo, Bamidele O, Vojinovic, Dina, Warren, Helen R, Xuan, Deng, Alver, Maris, Boissel, Mathilde, Chai, Jin-Fang, Chen, Xu, Christensen, Kaare, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Girotto, Giorgia, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Kühnel, Brigitte, Laguzzi, Federica, Li, Xiaoyin, Lyytikäinen, Leo-Pekka, Nolte, Ilja M, Poveda, Alaitz, Rauramaa, Rainer, Riaz, Muhammad, Rueedi, Rico, Shu, Xiao-Ou, Snieder, Harold, Sofer, Tamar, Takeuchi, Fumihiko, Verweij, Niek, Ware, Erin B, Weiss, Stefan, Yanek, Lisa R, Amin, Najaf, Arking, Dan E, Arnett, Donna K, Bergmann, Sven, Boerwinkle, Eric, Brody, Jennifer A, Broeckel, Ulrich, Brumat, Marco, Burke, Gregory, Cabrera, Claudia P, Canouil, Mickaël, Chee, Miao Li, Chen, Yii-Der Ida, Cocca, Massimiliano, Connell, John, de Silva, H Janaka, de Vries, Paul S, Eiriksdottir, Gudny, Faul, Jessica D, Fisher, Virginia, Forrester, Terrence, Fox, Ervin F, Friedlander, Yechiel, Gao, He, Gigante, Bruna, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B, He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven, Ikram, M Arfan, Irvin, Marguerite R, Kähönen, Mika, Kavousi, Maryam, de Las Fuentes, Lisa, de Las Fuentes, Lisa, Sung, Yun Ju, Noordam, Raymond, Winkler, Thomas, Feitosa, Mary F, Schwander, Karen, Bentley, Amy R, Brown, Michael R, Guo, Xiuqing, Manning, Alisa, Chasman, Daniel I, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Campbell, Archie, Cheng, Ching-Yu, Dorajoo, Rajkumar, Hartwig, Fernando P, Horimoto, ARVR, Li, Changwei, Li-Gao, Ruifang, Liu, Yongmei, Marten, Jonathan, Musani, Solomon K, Ntalla, Ioanna, Rankinen, Tuomo, Richard, Melissa, Sim, Xueling, Smith, Albert V, Tajuddin, Salman M, Tayo, Bamidele O, Vojinovic, Dina, Warren, Helen R, Xuan, Deng, Alver, Maris, Boissel, Mathilde, Chai, Jin-Fang, Chen, Xu, Christensen, Kaare, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Girotto, Giorgia, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Kühnel, Brigitte, Laguzzi, Federica, Li, Xiaoyin, Lyytikäinen, Leo-Pekka, Nolte, Ilja M, Poveda, Alaitz, Rauramaa, Rainer, Riaz, Muhammad, Rueedi, Rico, Shu, Xiao-Ou, Snieder, Harold, Sofer, Tamar, Takeuchi, Fumihiko, Verweij, Niek, Ware, Erin B, Weiss, Stefan, Yanek, Lisa R, Amin, Najaf, Arking, Dan E, Arnett, Donna K, Bergmann, Sven, Boerwinkle, Eric, Brody, Jennifer A, Broeckel, Ulrich, Brumat, Marco, Burke, Gregory, Cabrera, Claudia P, Canouil, Mickaël, Chee, Miao Li, Chen, Yii-Der Ida, Cocca, Massimiliano, Connell, John, de Silva, H Janaka, de Vries, Paul S, Eiriksdottir, Gudny, Faul, Jessica D, Fisher, Virginia, Forrester, Terrence, Fox, Ervin F, Friedlander, Yechiel, Gao, He, Gigante, Bruna, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B, He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven, Ikram, M Arfan, Irvin, Marguerite R, Kähönen, Mika, and Kavousi, Maryam
Abstract: Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
Published: 2021

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