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2. Text Messaging and Home Blood Pressure Monitoring for Patients with Uncontrolled Hypertension: Proposal for a Feasibility Pilot Randomized Controlled Trial

Author

Campos, Claudia L, Jones, Deanna, Snively, Beverly M, Rocco, Michael, Pedley, Carolyn, Atwater, Sara, and Moore, Justin B

Subjects
Medicine, Computer applications to medicine. Medical informatics, R858-859.7
Abstract

BackgroundA decrease in blood pressure, even modestly (ie, 2 mmHg), lowers cardiovascular morbidity and mortality. Low patient adherence to antihypertensive medication is the most significant modifiable patient-related barrier to achieving controlled blood pressure. Preliminary studies have shown that SMS text messaging and home blood pressure monitoring (HBPM) can be effective in promoting medication adherence and blood pressure control. The best strategy to engage with older patients of low socioeconomic status who are low adopters of technology and disproportionally affected by uncontrolled hypertension is still unknown. ObjectiveThe objective of this study is to improve blood pressure control in the older, low socioeconomic status population. The study will test two aims: First, we aim to evaluate the feasibility of conducting a randomized controlled trial by using an SMS-based approach among nonadherent, older patients of low socioeconomic status who have uncontrolled hypertension. Feasibility will be assessed in terms of recruitment rates per month (primary outcome); patient acceptability will be evaluated by monitoring retention rates and SMS response rates and using the validated Systems Usability Scale (secondary outcomes). Second, we aim to estimate the effects of the SMS approach on lowering blood pressure and adherence to antihypertensive medications. MethodsWe will recruit 24 patients of low socioeconomic status with uncontrolled hypertension (systolic BP>140 mmHg or diastolic BP>90 mmHg) showing low medication adherence and taking at least two antihypertensives, who have presented to two outpatient clinics of Wake Forest Baptist Health (Winston Salem, North Carolina, USA). Participants will be randomly assigned to either SMS and HBPM (n=12) or usual care and HBPM (n=12) intervention. Clinicians adjusting the patients’ medications will be blinded to the study assignment. Text messages will be sent from a secure platform to assess medication adherence and HBPM on a weekly basis. The content and delivery frequency of the proposed SMS intervention are based on input from three focus groups conducted in Spring 2019. Participants in both study arms will receive education on HBPM and using an HBPM device. We hypothesize that we will successfully recruit 24 participants and the intervention will be acceptable to the participants. It will also improve medication adherence (assessed by question Medication Adherence Questionnaire scores) and blood pressure control. ResultsOur study was funded in July 2020. As of May 2021, we have enrolled 6 participants. ConclusionsOur findings will help design a larger efficacy trial to advance the field of eHealth delivery systems particularly for older adults of low socioeconomic status. This study addresses a highly significant topic and targets a population of high morbidity and mortality that has been traditionally underrepresented in clinical trials. Trial RegistrationClinicalTrials.gov NCT03596242; https://clinicaltrials.gov/ct2/show/NCT03596242 International Registered Report Identifier (IRRID)PRR1-10.2196/18984

Published
2021
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3. Rare coding variants in RCN3 are associated with blood pressure

Author

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, Morrison, Alanna C, Levy, Daniel, Chakravarti, Aravinda, Arnett, Donna K, and Zhu, Xiaofeng

Subjects
Biological Sciences, Genetics, Hypertension, Human Genome, Precision Medicine, Biotechnology, Cardiovascular, Minority Health, 2.1 Biological and endogenous factors, Good Health and Well Being, Blood Pressure, Genetic Linkage, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Whole Genome Sequencing, Rare variant analysis, Blood pressure, Whole genome sequencing, Samoan Obesity, Lifestyle and Genetic Adaptations Study (OLaGA) Group, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Information and Computing Sciences, Medical and Health Sciences, Bioinformatics, Biological sciences, Biomedical and clinical sciences
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

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

Author

Kelly, Tanika N, Sun, Xiao, He, Karen Y, Brown, Michael R, Taliun, Sarah A Gagliano, Hellwege, Jacklyn N, Irvin, Marguerite R, Mi, Xuenan, Brody, Jennifer A, Franceschini, Nora, Guo, Xiuqing, Hwang, Shih-Jen, de Vries, Paul S, Gao, Yan, Moscati, Arden, Nadkarni, Girish N, Yanek, Lisa R, Elfassy, Tali, Smith, Jennifer A, Chung, Ren-Hua, Beitelshees, Amber L, Patki, Amit, Aslibekyan, Stella, Blobner, Brandon M, Peralta, Juan M, Assimes, Themistocles L, Palmas, Walter R, Liu, Chunyu, Bress, Adam P, Huang, Zhijie, Becker, Lewis C, Hwa, Chii-Min, O’Connell, Jeffrey R, Carlson, Jenna C, Warren, Helen R, Das, Sayantan, Giri, Ayush, Martin, Lisa W, Johnson, W Craig, Fox, Ervin R, Bottinger, Erwin P, Razavi, Alexander C, Vaidya, Dhananjay, Chuang, Lee-Ming, Chang, Yen-Pei C, Naseri, Take, Jain, Deepti, Kang, Hyun Min, Hung, Adriana M, Srinivasasainagendra, Vinodh, Snively, Beverly M, Gu, Dongfeng, Montasser, May E, Reupena, Muagututi A Sefuiva, Heavner, Benjamin D, LeFaive, Jonathon, Hixson, James E, Rice, Kenneth M, Wang, Fei Fei, Nielsen, Jonas B, Huang, Jianfeng, Khan, Alyna T, Zhou, Wei, Nierenberg, Jovia L, Laurie, Cathy C, Armstrong, Nicole D, Shi, Mengyao, Pan, Yang, Stilp, Adrienne M, Emery, Leslie, Wong, Quenna, Hawley, Nicola L, Minster, Ryan L, Curran, Joanne E, Munroe, Patricia B, Weeks, Daniel E, North, Kari E, Tracy, Russell P, Kenny, Eimear E, Shimbo, Daichi, Chakravarti, Aravinda, Rich, Stephen S, Reiner, Alex P, Blangero, John, Redline, Susan, Mitchell, Braxton D, Rao, Dabeeru C, Chen, Yii-Der Ida, Kardia, Sharon LR, Kaplan, Robert C, Mathias, Rasika A, He, Jiang, Psaty, Bruce M, Fornage, Myriam, Loos, Ruth JF, Correa, Adolfo, Boerwinkle, Eric, Rotter, Jerome I, Kooperberg, Charles, and Edwards, Todd L

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Biotechnology, Hypertension, Human Genome, Genetics, 2.1 Biological and endogenous factors, Cardiovascular, Good Health and Well Being, Blood Pressure, Genome-Wide Association Study, Genomics, Humans, Polymorphism, Single Nucleotide, Precision Medicine, allele, blood pressure, genome, hypertension, whole genome sequencing, Samoan Obesity, Lifestyle, and Genetic Adaptations Study (OLaGA) Group, ‡ NHLBI Trans-Omics for Precision Medicine TOPMed) Consortium, Cardiorespiratory Medicine and Haematology, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences
Abstract

BackgroundThe 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.MethodsWe 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.ResultsTwo blood pressure signals achieved genome-wide significance in meta-analyses of stage-1 and stage-2 single variant findings (P

Published
2022

6. A genetic association study of circulating coagulation factor VIII and von Willebrand factor levels

Author

Abe, Namiko, Abecasis, Gonçalo, Aguet, Francois, Albert, Christine, Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Deborah, Ardlie, Kristin, Arking, Dan, Arnett, Donna K, Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Ayas, Najib, Balasubramanian, Adithya, Barnard, John, Barnes, Kathleen, Barr, R. Graham, Barron-Casella, Emily, Barwick, Lucas, Beaty, Terri, Beck, Gerald, Becker, Diane, Becker, Lewis, Beer, Rebecca, Beitelshees, Amber, Benjamin, Emelia, Benos, Takis, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Blue, Nathan, Boerwinkle, Eric, Bowden, Donald W., Bowler, Russell, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Brown, Deborah, Bunting, Karen, Burchard, Esteban, Bustamante, Carlos, Buth, Erin, Cade, Brian, Cardwell, Jonathan, Carey, Vincent, Carrier, Julie, Carson, April P., Carty, Cara, Casaburi, Richard, Casas Romero, Juan P, Casella, James, Castaldi, Peter, Chaffin, Mark, Chang, Christy, Chang, Yi-Cheng, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Ida Chen, Yii-Der, Cho, Michael, Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Chung, Ren-Hua, Clish, Clary, Comhair, Suzy, Conomos, Matthew, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L. Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, David, Sean, Davis, Colleen, Daya, Michelle, de Andrade, Mariza, de las Fuentes, Lisa, de Vries, Paul, DeBaun, Michael, Deka, Ranjan, DeMeo, Dawn, Devine, Scott, Dinh, Huyen, Doddapaneni, Harsha, Duan, Qing, Dugan-Perez, Shannon, Duggirala, Ravi, Durda, Jon Peter, Dutcher, Susan K., Eaton, Charles, Ekunwe, Lynette, El Boueiz, Adel, Ellinor, Patrick, Emery, Leslie, Erzurum, Serpil, Farber, Charles, Farek, Jesse, Fingerlin, Tasha, Flickinger, Matthew, Fornage, Myriam, Franceschini, Nora, Frazar, Chris, Fu, Mao, Fullerton, Stephanie M., Fulton, Lucinda, Gabriel, Stacey, Gan, Weiniu, Gao, Shanshan, Gao, Yan, Gass, Margery, Geiger, Heather, Gelb, Bruce, Geraci, Mark, Germer, Soren, Gerszten, Robert, Ghosh, Auyon, Gibbs, Richard, Gignoux, Chris, Gladwin, Mark, Glahn, David, Gogarten, Stephanie, Gong, Da-Wei, Goring, Harald, Graw, Sharon, Gray, Kathryn J., Grine, Daniel, Gross, Colin, Gu, C. Charles, Guan, Yue, Guo, Xiuqing, Gupta, Namrata, Haessler, Jeff, Hall, Michael, Han, Yi, Hanly, Patrick, Harris, Daniel, Hawley, Nicola L., He, Jiang, Heavner, Ben, Heckbert, Susan, Hernandez, Ryan, Herrington, David, Hersh, Craig, Hidalgo, Bertha, Hixson, James, Hobbs, Brian, Hokanson, John, Hong, Elliott, Hoth, Karin, Hsiung, Chao (Agnes), Hu, Jianhong, Hung, Yi-Jen, Huston, Haley, Hwu, Chii Min, Irvin, Marguerite Ryan, Jackson, Rebecca, Jain, Deepti, Jaquish, Cashell, Johnsen, Jill, Johnson, Andrew, Johnson, Craig, Johnston, Rich, Jones, Kimberly, Kang, Hyun Min, Kaplan, Robert, Kardia, Sharon, Kelly, Shannon, Kenny, Eimear, Kessler, Michael, Khan, Alyna, Khan, Ziad, Kim, Wonji, Kimoff, John, Kinney, Greg, Konkle, Barbara, Kooperberg, Charles, Kramer, Holly, Lange, Christoph, Lange, Ethan, Lange, Leslie, Laurie, Cathy, Laurie, Cecelia, LeBoff, Meryl, Lee, Jiwon, Lee, Sandra, Lee, Wen-Jane, LeFaive, Jonathon, Levine, David, Levy, Dan, Lewis, Joshua, Li, Xiaohui, Li, Yun, Lin, Henry, Lin, Honghuang, Lin, Xihong, Liu, Simin, Liu, Yongmei, Liu, Yu, Loos, Ruth J. F., Lubitz, Steven, Lunetta, Kathryn, Luo, James, Magalang, Ulysses, Mahaney, Michael, Make, Barry, Manichaikul, Ani, Manning, Alisa, Manson, JoAnn, Martin, Lisa, Marton, Melissa, Mathai, Susan, Mathias, Rasika, May, Susanne, McArdle, Patrick, McDonald, Merry-Lynn, McFarland, Sean, McGarvey, Stephen, McGoldrick, Daniel, McHugh, Caitlin, McNeil, Becky, Mei, Hao, Meigs, James, Menon, Vipin, Mestroni, Luisa, Metcalf, Ginger, Meyers, Deborah A, Mignot, Emmanuel, Mikulla, Julie, Min, Nancy, Minear, Mollie, Minster, Ryan L, Mitchell, Braxton D., Moll, Matt, Momin, Zeineen, Montasser, May E., Montgomery, Courtney, Muzny, Donna, Mychaleckyj, Josyf C, Nadkarni, Girish, Naik, Rakhi, Naseri, Take, Natarajan, Pradeep, Nekhai, Sergei, Nelson, Sarah C., Neltner, Bonnie, Nessner, Caitlin, Nickerson, Deborah, Nkechinyere, Osuji, North, Kari, O'Connell, Jeff, O'Connor, Tim, Ochs-Balcom, Heather, Okwuonu, Geoffrey, Pack, Allan, Paik, David T., Palmer, Nicholette, Pankow, James, Papanicolaou, George, Parker, Cora, Peloso, Gina, Peralta, Juan Manuel, Perez, Marco, Perry, James, Peters, Ulrike, Peyser, Patricia, Phillips, Lawrence S, Pleiness, Jacob, Pollin, Toni, Post, Wendy, Becker, Julia Powers, Boorgula, Meher Preethi, Preuss, Michael, Psaty, Bruce, Qasba, Pankaj, Qiao, Dandi, Qin, Zhaohui, Rafaels, Nicholas, Raffield, Laura, Rajendran, Mahitha, Ramachandran, Vasan S., Rao, D. C., Rasmussen-Torvik, Laura, Ratan, Aakrosh, Redline, Susan, Reed, Robert, Reeves, Catherine, Regan, Elizabeth, Reiner, Alex, Reupena, Muagututi‘a Sefuiva, Rice, Ken, Rich, Stephen, Robillard, Rebecca, Robine, Nicolas, Roden, Dan, Roselli, Carolina, Rotter, Jerome, Ruczinski, Ingo, Runnels, Alexi, Russell, Pamela, Ruuska, Sarah, Ryan, Kathleen, Sabino, Ester Cerdeira, Saleheen, Danish, Salimi, Shabnam, Salvi, Sejal, Salzberg, Steven, Sandow, Kevin, Sankaran, Vijay G., Santibanez, Jireh, Schwander, Karen, Schwartz, David, Sciurba, Frank, Seidman, Christine, Seidman, Jonathan, Sériès, Frédéric, Sheehan, Vivien, Sherman, Stephanie L., Shetty, Amol, Shetty, Aniket, Hui-Heng Sheu, Wayne, Shoemaker, M. Benjamin, Silver, Brian, Silverman, Edwin, Skomro, Robert, Smith, Albert Vernon, Smith, Jennifer, Smith, Josh, Smith, Nicholas, Smith, Tanja, Smoller, Sylvia, Snively, Beverly, Snyder, Michael, Sofer, Tamar, Sotoodehnia, Nona, Stilp, Adrienne M., Storm, Garrett, Streeten, Elizabeth, Su, Jessica Lasky, Sung, Yun Ju, Sylvia, Jody, Szpiro, Adam, Taliun, Daniel, Tang, Hua, Taub, Margaret, Taylor, Kent D., Taylor, Matthew, Taylor, Simeon, Telen, Marilyn, Thornton, Timothy A., Threlkeld, Machiko, Tinker, Lesley, Tirschwell, David, Tishkoff, Sarah, Tiwari, Hemant, Tong, Catherine, Tracy, Russell, Tsai, Michael, Vaidya, Dhananjay, Van Den Berg, David, VandeHaar, Peter, Vrieze, Scott, Walker, Tarik, Wallace, Robert, Walts, Avram, Wang, Fei Fei, Wang, Heming, Wang, Jiongming, Watson, Karol, Watt, Jennifer, Weeks, Daniel E., Weinstock, Joshua, Weir, Bruce, Weiss, Scott T, Weng, Lu-Chen, Wessel, Jennifer, Willer, Cristen, Williams, Kayleen, Williams, L. Keoki, Wilson, Carla, Wilson, James, Winterkorn, Lara, Wong, Quenna, Wu, Joseph, Xu, Huichun, Yanek, Lisa, Yang, Ivana, Yu, Ketian, Zekavat, Seyedeh Maryam, Zhang, Yingze, Zhao, Snow Xueyan, Zhao, Wei, Zhu, Xiaofeng, Ziv, Elad, Zody, Michael, Zoellner, Sebastian, Lindstrom, Sara, Wang, Lu, Smith, Erin N., Gordon, William, van Hylckama Vlieg, Astrid, Brody, Jennifer A., Pattee, Jack W., Haessler, Jeffrey, Brumpton, Ben M., Chasman, Daniel I., Suchon, Pierre, Chen, Ming-Huei, Turman, Constance, Germain, Marine, Wiggins, Kerri L., MacDonald, James, Braekkan, Sigrid K., Armasu, Sebastian M., Pankratz, Nathan, Jackson, Rabecca D., Nielsen, Jonas B., Giulianini, Franco, Puurunen, Marja K., Ibrahim, Manal, Heckbert, Susan R., Bammler, Theo K., Frazer, Kelly A., McCauley, Bryan M., Taylor, Kent, Pankow, James S., Reiner, Alexander P., Gabrielsen, Maiken E., Deleuze, Jean-François, O'Donnell, Chris J., Kim, Jihye, McKnight, Barbara, Kraft, Peter, Hansen, John-Bjarne, Rosendaal, Frits R., Heit, John A., Psaty, Bruce M., Tang, Weihong, Hveem, Kristian, Ridker, Paul M., Morange, Pierre-Emmanuel, Johnson, Andrew D., Kabrhel, Christopher, AlexandreTrégouët, David, Smith, Nicholas L., de Vries, Paul S., Reventun, Paula, Brown, Michael R., Heath, Adam S., Huffman, Jennifer E., Le, Ngoc-Quynh, Bebo, Allison, Temprano-Sagrera, Gerard, Raffield, Laura M., Ozel, Ayse Bilge, Thibord, Florian, Lewis, Joshua P., Rodriguez, Benjamin A. T., Polasek, Ozren, Yanek, Lisa R., Carrasquilla, German D., Marioni, Riccardo E., Kleber, Marcus E., Trégouët, David-Alexandre, Yao, Jie, Li-Gao, Ruifang, Joshi, Peter K., Trompet, Stella, Martinez-Perez, Angel, Ghanbari, Mohsen, Howard, Tom E., Reiner, Alex P., Arvanitis, Marios, Ryan, Kathleen A., Bartz, Traci M., Rudan, Igor, Faraday, Nauder, Linneberg, Allan, Davies, Gail, Delgado, Graciela E., Klaric, Lucija, Noordam, Raymond, van Rooij, Frank, Curran, Joanne E., Wheeler, Marsha M., Osburn, William O., O'Connell, Jeffrey R., Beswick, Andrew, Kolcic, Ivana, Souto, Juan Carlos, Becker, Lewis C., Hansen, Torben, Doyle, Margaret F., Harris, Sarah E., Moissl, Angela P., Rich, Stephen S., Campbell, Harry, Stott, David J., Soria, Jose Manuel, de Maat, Moniek P. M., Brody, Lawrence C., Auer, Paul L., Ben-Shlomo, Yoav, Hayward, Caroline, Mathias, Rasika A., Kilpeläinen, Tuomas O., Lange, Leslie A., Cox, Simon R., März, Winfried, Rotter, Jerome I., Mook-Kanamori, Dennis O., Wilson, James F., van der Harst, Pim, Jukema, J. Wouter, Ikram, M. Arfan, Desch, Karl C., Sabater-Lleal, Maria, Lowenstein, Charles J., and Morrison, Alanna C.

Published
2024
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7. Dual-Outcome Intention-to-Treat Analyses in the Women's Health Initiative Randomized Controlled Hormone Therapy Trials.

Author

Prentice, Ross L, Aragaki, Aaron K, Chlebowski, Rowan T, Zhao, Shanshan, Anderson, Garnet L, Rossouw, Jacques E, Wallace, Robert, Banack, Hailey, Shadyab, Aladdin H, Qi, Lihong, Snively, Beverly M, Gass, Margery, and Manson, JoAnn E

Subjects
Humans, Gallbladder Diseases, Cardiovascular Diseases, Estrogens, Conjugated (USP), Estrogen Replacement Therapy, Incidence, Risk Factors, Postmenopause, Aged, Middle Aged, United States, Female, Fractures, Bone, Randomized Controlled Trials as Topic, Medroxyprogesterone Acetate, Intention to Treat Analysis, Cox model, cancer, cardiovascular disease, diabetes, dual outcomes, fractures, hazard ratio, menopausal hormone therapy, Clinical Research, Clinical Trials and Supportive Activities, Estrogen, Contraception/Reproduction, Aging, Good Health and Well Being, Mathematical Sciences, Medical and Health Sciences, Epidemiology
Abstract

Dual-outcome intention-to-treat hazard rate analyses have potential to complement single-outcome analyses for the evaluation of treatments or exposures in relation to multivariate time-to-response outcomes. Here we consider pairs formed from important clinical outcomes to obtain further insight into influences of menopausal hormone therapy on chronic disease. As part of the Women's Health Initiative, randomized, placebo-controlled hormone therapy trials of conjugated equine estrogens (CEE) among posthysterectomy participants and of these same estrogens plus medroxyprogesterone acetate (MPA) among participants with an intact uterus were carried out at 40 US clinical centers (1993-2016). These data provide the context for analyses covering the trial intervention periods and a nearly 20-year (median) cumulative duration of follow-up. The rates of multiple outcome pairs were significantly influenced by hormone therapy, especially over cumulative follow-up, providing potential clinical and mechanistic insights. For example, among women randomized to either regimen, hazard ratios for pairs defined by fracture during intervention followed by death from any cause were reduced and hazard ratios for pairs defined by gallbladder disease followed by death were increased, though these findings may primarily reflect single-outcome associations. In comparison, hazard ratios for diabetes followed by death were reduced with CEE but not with CEE + MPA, and those for hypertension followed by death were increased with CEE + MPA but not with CEE.

Published
2020

8. Epigenome-wide DNA methylation association study of circulating IgE levels identifies novel targets for asthma

Author

Abe, Namiko, Abecasis, Gonçalo, Aguet, Francois, Albert, Christine, Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Deborah, Ardlie, Kristin, Arking, Dan, Arnett, Donna K., Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Ayas, Najib, Balasubramanian, Adithya, Barnard, John, Barnes, Kathleen, Barr, R. Graham, Barron-Casella, Emily, Barwick, Lucas, Beaty, Terri, Beck, Gerald, Becker, Diane, Becker, Lewis, Beer, Rebecca, Beitelshees, Amber, Benjamin, Emelia, Benos, Takis, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Blue, Nathan, Boerwinkle, Eric, Bowden, Donald W., Bowler, Russell, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Brown, Deborah, Bunting, Karen, Burchard, Esteban, Bustamante, Carlos, Buth, Erin, Cade, Brian, Cardwell, Jonathan, Carey, Vincent, Carrier, Julie, Carson, April P., Carty, Cara, Casaburi, Richard, Casas Romero, Juan P., Casella, James, Castaldi, Peter, Chaffin, Mark, Chang, Christy, Chang, Yi-Cheng, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Ida Chen, Yii-Der, Cho, Michael, Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Chung, Ren-Hua, Clish, Clary, Comhair, Suzy, Conomos, Matthew, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L. Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, David, Sean, Davis, Colleen, Daya, Michelle, de Andrade, Mariza, de las Fuentes, Lisa, de Vries, Paul, DeBaun, Michael, Deka, Ranjan, DeMeo, Dawn, Devine, Scott, Dinh, Huyen, Doddapaneni, Harsha, Duan, Qing, Dugan-Perez, Shannon, Duggirala, Ravi, Durda, Jon Peter, Dutcher, Susan K., Eaton, Charles, Ekunwe, Lynette, El Boueiz, Adel, Ellinor, Patrick, Emery, Leslie, Erzurum, Serpil, Farber, Charles, Farek, Jesse, Fingerlin, Tasha, Flickinger, Matthew, Fornage, Myriam, Franceschini, Nora, Frazar, Chris, Fu, Mao, Fullerton, Stephanie M., Fulton, Lucinda, Gabriel, Stacey, Gan, Weiniu, Gao, Shanshan, Gao, Yan, Gass, Margery, Geiger, Heather, Gelb, Bruce, Geraci, Mark, Germer, Soren, Gerszten, Robert, Ghosh, Auyon, Gibbs, Richard, Gignoux, Chris, Gladwin, Mark, Glahn, David, Gogarten, Stephanie, Gong, Da-Wei, Goring, Harald, Graw, Sharon, Gray, Kathryn J., Grine, Daniel, Gross, Colin, Gu, C. Charles, Guan, Yue, Guo, Xiuqing, Gupta, Namrata, Haessler, Jeff, Hall, Michael, Han, Yi, Hanly, Patrick, Harris, Daniel, Hawley, Nicola L., He, Jiang, Heavner, Ben, Heckbert, Susan, Hernandez, Ryan, Herrington, David, Hersh, Craig, Hidalgo, Bertha, Hixson, James, Hobbs, Brian, Hokanson, John, Hong, Elliott, Hoth, Karin, Hsiung, Chao (Agnes), Hu, Jianhong, Hung, Yi-Jen, Huston, Haley, Hwu, Chii Min, Irvin, Marguerite Ryan, Jackson, Rebecca, Jain, Deepti, Jaquish, Cashell, Johnsen, Jill, Johnson, Andrew, Johnson, Craig, Johnston, Rich, Jones, Kimberly, Kang, Hyun Min, Kaplan, Robert, Kardia, Sharon, Kelly, Shannon, Kenny, Eimear, Kessler, Michael, Khan, Alyna, Khan, Ziad, Kim, Wonji, Kimoff, John, Kinney, Greg, Konkle, Barbara, Kooperberg, Charles, Kramer, Holly, Lange, Christoph, Lange, Ethan, Lange, Leslie, Laurie, Cathy, Laurie, Cecelia, LeBoff, Meryl, Lee, Jiwon, Lee, Sandra, Lee, Wen-Jane, LeFaive, Jonathon, Levine, David, Levy, Daniel, Lewis, Joshua, Li, Xiaohui, Li, Yun, Lin, Henry, Lin, Honghuang, Lin, Xihong, Liu, Simin, Liu, Yongmei, Liu, Yu, Loos, Ruth J.F., Lubitz, Steven, Lunetta, Kathryn, Luo, James, Magalang, Ulysses, Mahaney, Michael, Make, Barry, Manichaikul, Ani, Manning, Alisa, Manson, JoAnn, Martin, Lisa, Marton, Melissa, Mathai, Susan, Mathias, Rasika, May, Susanne, McArdle, Patrick, McDonald, Merry-Lynn, McFarland, Sean, McGarvey, Stephen, McGoldrick, Daniel, McHugh, Caitlin, McNeil, Becky, Mei, Hao, Meigs, James, Menon, Vipin, Mestroni, Luisa, Metcalf, Ginger, Meyers, Deborah A., Mignot, Emmanuel, Mikulla, Julie, Min, Nancy, Minear, Mollie, Minster, Ryan L., Mitchell, Braxton D., Moll, Matt, Momin, Zeineen, Montasser, May E., Montgomery, Courtney, Muzny, Donna, Mychaleckyj, Josyf C., Nadkarni, Girish, Naik, Rakhi, Naseri, Take, Natarajan, Pradeep, Nekhai, Sergei, Nelson, Sarah C., Neltner, Bonnie, Nessner, Caitlin, Nickerson, Deborah, Nkechinyere, Osuji, North, Kari, O'Connell, Jeff, O'Connor, Tim, Ochs-Balcom, Heather, Okwuonu, Geoffrey, Pack, Allan, Paik, David T., Palmer, Nicholette, Pankow, James, Papanicolaou, George, Parker, Cora, Peloso, Gina, Peralta, Juan Manuel, Perez, Marco, Perry, James, Peters, Ulrike, Peyser, Patricia, Phillips, Lawrence S., Pleiness, Jacob, Pollin, Toni, Post, Wendy, Powers Becker, Julia, Preethi Boorgula, Meher, Preuss, Michael, Psaty, Bruce, Qasba, Pankaj, Qiao, Dandi, Qin, Zhaohui, Rafaels, Nicholas, Raffield, Laura, Rajendran, Mahitha, Ramachandran, Vasan S., Rao, D.C., Rasmussen-Torvik, Laura, Ratan, Aakrosh, Redline, Susan, Reed, Robert, Reeves, Catherine, Regan, Elizabeth, Reiner, Alex, Reupena, Muagututi‘a Sefuiva, Rice, Ken, Rich, Stephen, Robillard, Rebecca, Robine, Nicolas, Roden, Dan, Roselli, Carolina, Rotter, Jerome, Ruczinski, Ingo, Runnels, Alexi, Russell, Pamela, Ruuska, Sarah, Ryan, Kathleen, Sabino, Ester Cerdeira, Saleheen, Danish, Salimi, Shabnam, Salvi, Sejal, Salzberg, Steven, Sandow, Kevin, Sankaran, Vijay G., Santibanez, Jireh, Schwander, Karen, Schwartz, David, Sciurba, Frank, Seidman, Christine, Seidman, Jonathan, Sériès, Frédéric, Sheehan, Vivien, Sherman, Stephanie L., Shetty, Amol, Shetty, Aniket, Sheu, Wayne Hui-Heng, Shoemaker, M. Benjamin, Silver, Brian, Silverman, Edwin, Skomro, Robert, Smith, Albert Vernon, Smith, Jennifer, Smith, Josh, Smith, Nicholas, Smith, Tanja, Smoller, Sylvia, Snively, Beverly, Snyder, Michael, Sofer, Tamar, Sotoodehnia, Nona, Stilp, Adrienne M., Storm, Garrett, Streeten, Elizabeth, Su, Jessica Lasky, Sung, Yun Ju, Sylvia, Jody, Szpiro, Adam, Taliun, Daniel, Tang, Hua, Taub, Margaret, Taylor, Kent, Taylor, Matthew, Taylor, Simeon, Telen, Marilyn, Thornton, Timothy A., Threlkeld, Machiko, Tinker, Lesley, Tirschwell, David, Tishkoff, Sarah, Tiwari, Hemant, Tong, Catherine, Tracy, Russell, Tsai, Michael, Vaidya, Dhananjay, Van Den Berg, David, VandeHaar, Peter, Vrieze, Scott, Walker, Tarik, Wallace, Robert, Walts, Avram, Wang, Fei Fei, Wang, Heming, Wang, Jiongming, Watson, Karol, Watt, Jennifer, Weeks, Daniel E., Weinstock, Joshua, Weir, Bruce, Weiss, Scott T., Weng, Lu-Chen, Wessel, Jennifer, Willer, Cristen, Williams, Kayleen, Williams, L. Keoki, Williams, Scott, Wilson, Carla, Wilson, James, Winterkorn, Lara, Wong, Quenna, Wu, Baojun, Wu, Joseph, Xu, Huichun, Yanek, Lisa, Yang, Ivana, Yu, Ketian, Zekavat, Seyedeh Maryam, Zhang, Yingze, Zhao, Snow Xueyan, Zhao, Wei, Zhu, Xiaofeng, Ziv, Elad, Zody, Michael, Zoellner, Sebastian, Recto, Kathryn, Kachroo, Priyadarshini, Huan, Tianxiao, Lee, Gha Young, Bui, Helena, Lee, Dong Heon, Gereige, Jessica, Yao, Chen, Hwang, Shih-Jen, Joehanes, Roby, O’Connor, George T., and DeMeo, Dawn L.

Published
2023
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9. Cognitive resilience among APOE ε4 carriers in the oldest old

Author

Hayden, Kathleen M, Gaussoin, Sarah A, Hunter, Jaimie C, Manson, JoAnn E, Sachs, Bonnie C, Shadyab, Aladdin H, Tindle, Hilary A, Mossavar‐Rahmani, Yasmin, Mozhui, Khyobeni, Snively, Beverly M, Rapp, Stephen R, and Resnick, Susan M

Subjects
Health Services and Systems, Health Sciences, Aging, Clinical Trials and Supportive Activities, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain Disorders, Alzheimer's Disease, Neurodegenerative, Acquired Cognitive Impairment, Prevention, Clinical Research, Cardiovascular, Behavioral and Social Science, Dementia, Aged, Aged, 80 and over, Apolipoprotein E4, Cholesterol, Cognition, Cognition Disorders, Female, Health Status, Humans, Logistic Models, Male, Middle Aged, Neuropsychological Tests, Odds Ratio, Resilience, Psychological, Risk Factors, APOE epsilon, cognitive resilience, mild cognitive impairment, oldest old, probable dementia, APOE ε, Clinical Sciences, Psychology, Cognitive Sciences, Geriatrics, Clinical sciences, Health services and systems, Clinical and health psychology
Abstract

ObjectivesRelatively few APOE ε4+ carriers survive to old age (age 80+) without cognitive impairment (CI); thus, little is known about distinguishing characteristics of resilient APOE ε4+ carriers. Herein, we describe the sociodemographic characteristics of a large sample of resilient APOE ε4+ women from the Women's Health Initiative Memory Study (WHIMS) and compare them to noncarriers and APOE ε4+ women who developed CI before age 80.MethodsWomen were recruited for clinical trials evaluating postmenopausal hormone therapy and incidence of dementia. During posttrial follow-up, cognitive status was adjudicated annually. Among 5716 women, we compared groups by APOE ε4 status using logistic regression, covarying for treatment, demographics, lifestyle, cardiovascular and physical function, well-being, and self-rated general health.ResultsAmong 557 APOE ε4+ women, those who survived to age 80+ without CI had higher baseline self-rated general health (odds ratio [OR]: 1.02; 95% confidence interval [CI], 1.01-1.04) and cognitive scores (OR: 1.18; 95% CI, 1.12-1.25) than those who did not reach age 80 without CI. Baseline high total cholesterol and low-density lipoprotein (LDL) levels were similar across APOE ε4+ groups but were higher compared with APOE ε4- women. Among women who survived to 80+ without CI, more APOE ε4+ women had a history of high total cholesterol (P = .003) and LDL cholesterol (OR: 1.01; 95% CI, 1.00-1.01). There were no differences in hypertension, diabetes, or other vascular risk factors in APOE ε4+ women compared with noncarriers.ConclusionsResults highlight the importance of baseline cognitive function and general health for late-life cognition among ε4+ women.

Published
2019

10. Leveraging linkage evidence to identify low-frequency and rare variants on 16p13 associated with blood pressure using TOPMed whole genome sequencing data

Author

He, Karen Y, Li, Xiaoyin, Kelly, Tanika N, Liang, Jingjing, Cade, Brian E, Assimes, Themistocles L, Becker, Lewis C, Beitelshees, Amber L, Bress, Adam P, Chang, Yen-Pei Christy, Chen, Yii-Der Ida, de Vries, Paul S, Fox, Ervin R, Franceschini, Nora, Furniss, Anna, Gao, Yan, Guo, Xiuqing, Haessler, Jeffrey, 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, Palmas, Walter, Reiner, Alex P, Shimbo, Daichi, Smith, Jennifer A, Snively, Beverly M, Yanek, Lisa R, Boerwinkle, Eric, Correa, Adolfo, Cupples, L Adrienne, He, Jiang, Kardia, Sharon LR, Kooperberg, Charles, Mathias, Rasika A, Mitchell, Braxton D, Psaty, Bruce M, Vasan, Ramachandran S, Rao, DC, Rich, Stephen S, Rotter, Jerome I, Wilson, James G, Chakravarti, Aravinda, Morrison, Alanna C, Levy, Daniel, Arnett, Donna K, Redline, Susan, and Zhu, Xiaofeng

Subjects
Biological Sciences, Genetics, Heart Disease, Biotechnology, Human Genome, Cardiovascular, Minority Health, Precision Medicine, Clinical Research, 2.1 Biological and endogenous factors, Good Health and Well Being, Alternative Splicing, Blood Pressure, Chromosomes, Human, Pair 16, Exome, Female, Follow-Up Studies, Genetic Linkage, Genetic Variation, Genome, Human, Genome-Wide Association Study, High-Throughput Nucleotide Sequencing, Humans, Male, RNA Splicing Factors, Recombinases, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Blood Pressure Working Group, Complementary and Alternative Medicine, Paediatrics and Reproductive Medicine, Genetics & Heredity, Reproductive medicine
Abstract

In this study, we investigated low-frequency and rare variants associated with blood pressure (BP) by focusing on a linkage region on chromosome 16p13. We used whole genome sequencing (WGS) data obtained through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program on 395 Cleveland Family Study (CFS) European Americans (CFS-EA). By analyzing functional coding variants and non-coding rare variants with CADD score > 10 residing within the chromosomal region in families with linkage evidence, we observed 25 genes with nominal statistical evidence (burden or SKAT p

Published
2019

12. Whole genome sequence analyses of brain imaging measures in the Framingham Study

Author

Sarnowski, Chloé, Satizabal, Claudia L, DeCarli, Charles, Pitsillides, Achilleas N, Cupples, L Adrienne, Vasan, Ramachandran S, Wilson, James G, Bis, Joshua C, Fornage, Myriam, Beiser, Alexa S, DeStefano, Anita L, Dupuis, Josée, Seshadri, Sudha, Arnett, Donna K, Becker, Diane, Bis, Joshua, Boerwinkle, Eric, Bowers, Michael, Bressler, Jan, Correa, Adolfo, DeStefano, Anita, Ding, Jingzhong ding, Fardo, David, Lugo, Alex Garcia, Glahn, David, Gonzalez, Hector, Hayden, Kathleen, Heckbert, Susan, Hoth, Karin, Hughes, Timothy, Jaquish, Cashell, Jian, Xueqiu, Knowles, Emma, Launer, Lenore, Lin, Honghuang, Longstreth, Will, Mayeux, Richard, Misra, Biswapriya, Mosley, Thomas, Nyquist, Paul, Olivier, Michael, Peprah, Emmanuel, Psaty, Bruce, Purcell, Shaun, Rotter, Jerome, Satizabal, Claudia, Schellenberg, Gerard, Simino, Jeannette, Smith, Jennifer, Smoller, Sylvia, Snively, Beverly, Sokolow, Sophie, Wehr, Kate, Yanek, Lisa, Yang, Qiong, Namiko, Abe, Goncalo, Abecasis, Christine, Albert, Nicholette (Nichole) Palmer, Allred, Laura, Almasy, Alvaro, Alonso, Seth, Ament, Peter, Anderson, Pramod, Anugu, Deborah, Applebaum-Bowden, Dan, Arking, Donna K, Arnett, Allison, Ashley-Koch, Stella, Aslibekyan, Tim, Assimes, Paul, Auer, Dimitrios, Avramopoulos, John, Barnard, Kathleen, Barnes, Graham, Barr R, Emily, Barron-Casella, Terri, Beaty, Diane, Becker, Lewis, Becker, Rebecca, Beer, Ferdouse, Begum, Amber, Beitelshees, Emelia, Benjamin, Marcos, Bezerra, Larry, Bielak, Joshua, Bis, Thomas, Blackwell, John, Blangero, Eric, Boerwinkle, Ingrid, Borecki, Russell, Bowler, Jennifer, Brody, Ulrich, Broeckel, Jai, Broome, Karen, Bunting, Esteban, Burchard, and Jonathan, Cardwell

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Genetics, Human Genome, Brain Disorders, Neurodegenerative, Biotechnology, Clinical Research, Aging, 2.1 Biological and endogenous factors, Neurological, Good Health and Well Being, Aged, Brain, Female, Genetic Variation, Genome-Wide Association Study, Humans, Magnetic Resonance Imaging, Male, Massachusetts, Middle Aged, Organ Size, Phenotype, Prospective Studies, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Neurocognitive Working Group, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveWe sought to identify rare variants influencing brain imaging phenotypes in the Framingham Heart Study by performing whole genome sequence association analyses within the Trans-Omics for Precision Medicine Program.MethodsWe performed association analyses of cerebral and hippocampal volumes and white matter hyperintensity (WMH) in up to 2,180 individuals by testing the association of rank-normalized residuals from mixed-effect linear regression models adjusted for sex, age, and total intracranial volume with individual variants while accounting for familial relatedness. We conducted gene-based tests for rare variants using (1) a sliding-window approach, (2) a selection of functional exonic variants, or (3) all variants.ResultsWe detected new loci in 1p21 for cerebral volume (minor allele frequency [MAF] 0.005, p = 10-8) and in 16q23 for hippocampal volume (MAF 0.05, p = 2.7 × 10-8). Previously identified associations in 12q24 for hippocampal volume (rs7294919, p = 4.4 × 10-4) and in 17q25 for WMH (rs7214628, p = 2.0 × 10-3) were confirmed. Gene-based tests detected associations (p ≤ 2.3 × 10-6) in new loci for cerebral (5q13, 8p12, 9q31, 13q12-q13, 15q24, 17q12, 19q13) and hippocampal volumes (2p12) and WMH (3q13, 4p15) including Alzheimer disease- (UNC5D) and Parkinson disease-associated genes (GBA). Pathway analyses evidenced enrichment of associated genes in immunity, inflammation, and Alzheimer disease and Parkinson disease pathways.ConclusionsWhole genome sequence-wide search reveals intriguing new loci associated with brain measures. Replication of novel loci is needed to confirm these findings.

Published
2018

13. Type 2 Diabetes Variants Disrupt Function of SLC16A11 through Two Distinct Mechanisms

Author

Rusu, Victor, Hoch, Eitan, Mercader, Josep M, Tenen, Danielle E, Gymrek, Melissa, Hartigan, Christina R, DeRan, Michael, von Grotthuss, Marcin, Fontanillas, Pierre, Spooner, Alexandra, Guzman, Gaelen, Deik, Amy A, Pierce, Kerry A, Dennis, Courtney, Clish, Clary B, Carr, Steven A, Wagner, Bridget K, Schenone, Monica, Ng, Maggie CY, Chen, Brian H, Consortium, MEDIA, Shriner, Daniel, Li, Jiang, Chen, Wei-Min, Guo, Xiuqing, Liu, Jiankang, Bielinski, Suzette J, Yanek, Lisa R, Nalls, Michael A, Comeau, Mary E, Rasmussen-Torvik, Laura J, Jensen, Richard A, Evans, Daniel S, Sun, Yan V, An, Ping, Patel, Sanjay R, Lu, Yingchang, Long, Jirong, Armstrong, Loren L, Wagenknecht, Lynne, Yang, Lingyao, Snively, Beverly M, Palmer, Nicholette D, Mudgal, Poorva, Langefeld, Carl D, Keene, Keith L, Freedman, Barry I, Mychaleckyj, Josyf C, Nayak, Uma, Raffel, Leslie J, Goodarzi, Mark O, Chen, Y-D Ida, Taylor, Herman A, Correa, Adolfo, Sims, Mario, Couper, David, Pankow, James S, Boerwinkle, Eric, Adeyemo, Adebowale, Doumatey, Ayo, Chen, Guanjie, Mathias, Rasika A, Vaidya, Dhananjay, Singleton, Andrew B, Zonderman, Alan B, Igo, Robert P, Sedor, John R, Consortium, the FIND, Kabagambe, Edmond K, Siscovick, David S, McKnight, Barbara, Rice, Kenneth, Liu, Yongmei, Hsueh, Wen-Chi, Zhao, Wei, Bielak, Lawrence F, Kraja, Aldi, Province, Michael A, Bottinger, Erwin P, Gottesman, Omri, Cai, Qiuyin, Zheng, Wei, Blot, William J, Lowe, William L, Pacheco, Jennifer A, Crawford, Dana C, Consortium, the eMERGE, Consortium, the DIAGRAM, Grundberg, Elin, Consortium, the MuTHER, Rich, Stephen S, Hayes, M Geoffrey, Shu, Xiao-Ou, Loos, Ruth JF, Borecki, Ingrid B, Peyser, Patricia A, Cummings, Steven R, and Psaty, Bruce M

Subjects
Biological Sciences, Genetics, Clinical Research, Diabetes, Digestive Diseases, Liver Disease, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Basigin, Cell Membrane, Chromosomes, Human, Pair 17, Diabetes Mellitus, Type 2, Gene Knockdown Techniques, Haplotypes, Hepatocytes, Heterozygote, Histone Code, Humans, Liver, Models, Molecular, Monocarboxylic Acid Transporters, MEDIA Consortium, SIGMA T2D Consortium, MCT11, SLC16A11, disease mechanism, fatty acid metabolism, genetics, lipid metabolism, monocarboxylates, precision medicine, solute carrier, type 2 diabetes, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Type 2 diabetes (T2D) affects Latinos at twice the rate seen in populations of European descent. We recently identified a risk haplotype spanning SLC16A11 that explains ∼20% of the increased T2D prevalence in Mexico. Here, through genetic fine-mapping, we define a set of tightly linked variants likely to contain the causal allele(s). We show that variants on the T2D-associated haplotype have two distinct effects: (1) decreasing SLC16A11 expression in liver and (2) disrupting a key interaction with basigin, thereby reducing cell-surface localization. Both independent mechanisms reduce SLC16A11 function and suggest SLC16A11 is the causal gene at this locus. To gain insight into how SLC16A11 disruption impacts T2D risk, we demonstrate that SLC16A11 is a proton-coupled monocarboxylate transporter and that genetic perturbation of SLC16A11 induces changes in fatty acid and lipid metabolism that are associated with increased T2D risk. Our findings suggest that increasing SLC16A11 function could be therapeutically beneficial for T2D. VIDEO ABSTRACT.

Published
2017

16. Genome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci Influencing Erythrocyte Traits and a Role for RBPMS in Erythropoiesis

Author

van Rooij, Frank JA, Qayyum, Rehan, Smith, Albert V, Zhou, Yi, Trompet, Stella, Tanaka, Toshiko, Keller, Margaux F, Chang, Li-Ching, Schmidt, Helena, Yang, Min-Lee, Chen, Ming-Huei, Hayes, James, Johnson, Andrew D, Yanek, Lisa R, Mueller, Christian, Lange, Leslie, Floyd, James S, Ghanbari, Mohsen, Zonderman, Alan B, Jukema, J Wouter, Hofman, Albert, van Duijn, Cornelia M, Desch, Karl C, Saba, Yasaman, Ozel, Ayse B, Snively, Beverly M, Wu, Jer-Yuarn, Schmidt, Reinhold, Fornage, Myriam, Klein, Robert J, Fox, Caroline S, Matsuda, Koichi, Kamatani, Naoyuki, Wild, Philipp S, Stott, David J, Ford, Ian, Slagboom, P Eline, Yang, Jaden, Chu, Audrey Y, Lambert, Amy J, Uitterlinden, André G, Franco, Oscar H, Hofer, Edith, Ginsburg, David, Hu, Bella, Keating, Brendan, Schick, Ursula M, Brody, Jennifer A, Li, Jun Z, Chen, Zhao, Zeller, Tanja, Guralnik, Jack M, Chasman, Daniel I, Peters, Luanne L, Kubo, Michiaki, Becker, Diane M, Li, Jin, Eiriksdottir, Gudny, Rotter, Jerome I, Levy, Daniel, Grossmann, Vera, Patel, Kushang V, Chen, Chien-Hsiun, Project, The BioBank Japan, Ridker, Paul M, Tang, Hua, Launer, Lenore J, Rice, Kenneth M, Li-Gao, Ruifang, Ferrucci, Luigi, Evans, Michelle K, Choudhuri, Avik, Trompouki, Eirini, Abraham, Brian J, Yang, Song, Takahashi, Atsushi, Kamatani, Yoichiro, Kooperberg, Charles, Harris, Tamara B, Jee, Sun Ha, Coresh, Josef, Tsai, Fuu-Jen, Longo, Dan L, Chen, Yuan-Tsong, Felix, Janine F, Yang, Qiong, Psaty, Bruce M, Boerwinkle, Eric, Becker, Lewis C, Mook-Kanamori, Dennis O, Wilson, James G, Gudnason, Vilmundur, O'Donnell, Christopher J, Dehghan, Abbas, Cupples, L Adrienne, Nalls, Michael A, Morris, Andrew P, Okada, Yukinori, Reiner, Alexander P, and Zon, Leonard I

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Hematology, Human Genome, Minority Health, 2.1 Biological and endogenous factors, Africa, Alleles, Animals, Bayes Theorem, Erythrocytes, Erythropoiesis, Ethnicity, Europe, Asia, Eastern, Female, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Male, RNA-Binding Proteins, Racial Groups, Zebrafish, BioBank Japan Project, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Genome-wide association studies (GWASs) have identified loci for erythrocyte traits in primarily European ancestry populations. We conducted GWAS meta-analyses of six erythrocyte traits in 71,638 individuals from European, East Asian, and African ancestries using a Bayesian approach to account for heterogeneity in allelic effects and variation in the structure of linkage disequilibrium between ethnicities. We identified seven loci for erythrocyte traits including a locus (RBPMS/GTF2E2) associated with mean corpuscular hemoglobin and mean corpuscular volume. Statistical fine-mapping at this locus pointed to RBPMS at this locus and excluded nearby GTF2E2. Using zebrafish morpholino to evaluate loss of function, we observed a strong in vivo erythropoietic effect for RBPMS but not for GTF2E2, supporting the statistical fine-mapping at this locus and demonstrating that RBPMS is a regulator of erythropoiesis. Our findings show the utility of trans-ethnic GWASs for discovery and characterization of genetic loci influencing hematologic traits.

Published
2017

19. Duration of Adulthood Overweight, Obesity, and Cancer Risk in the Women's Health Initiative: A Longitudinal Study from the United States.

Author

Arnold, Melina, Jiang, Luohua, Stefanick, Marcia L, Johnson, Karen C, Lane, Dorothy S, LeBlanc, Erin S, Prentice, Ross, Rohan, Thomas E, Snively, Beverly M, Vitolins, Mara, Zaslavsky, Oleg, Soerjomataram, Isabelle, and Anton-Culver, Hoda

Subjects
Humans, Neoplasms, Obesity, Body Mass Index, Proportional Hazards Models, Risk Factors, Longitudinal Studies, Prospective Studies, Pregnancy, Time Factors, Adolescent, Adult, Middle Aged, United States, Female, Overweight, Young Adult, Breast Cancer, Cancer, Nutrition, Aging, Clinical Research, Patient Safety, Prevention, Stroke, Metabolic and Endocrine, General & Internal Medicine, Medical and Health Sciences
Abstract

BackgroundHigh body mass index (BMI) has become the leading risk factor of disease burden in high-income countries. While recent studies have suggested that the risk of cancer related to obesity is mediated by time, insights into the dose-response relationship and the cumulative impact of overweight and obesity during the life course on cancer risk remain scarce. To our knowledge, this study is the first to assess the impact of adulthood overweight and obesity duration on the risk of cancer in a large cohort of postmenopausal women.Methods and findingsParticipants from the observational study of the Women's Health Initiative (WHI) with BMI information from at least three occasions during follow-up, free of cancer at baseline, and with complete covariate information were included (n = 73,913). Trajectories of BMI across ages were estimated using a quadratic growth model; overweight duration (BMI ≥ 25 kg/m2), obesity duration (BMI ≥ 30 kg/m2), and weighted cumulative overweight and obese years, which take into account the degree of overweight and obesity over time (a measure similar to pack-years of cigarette smoking), were calculated using predicted BMIs. Cox proportional hazard models were applied to determine the cancer risk associated with overweight and obesity duration. In secondary analyses, the influence of important effect modifiers and confounders, such as smoking status, postmenopausal hormone use, and ethnicity, was assessed. A longer duration of overweight was significantly associated with the incidence of all obesity-related cancers (hazard ratio [HR] per 10-y increment: 1.07, 95% CI 1.06-1.09). For postmenopausal breast and endometrial cancer, every 10-y increase in adulthood overweight duration was associated with a 5% and 17% increase in risk, respectively. On adjusting for intensity of overweight, these figures rose to 8% and 37%, respectively. Risks of postmenopausal breast and endometrial cancer related to overweight duration were much more pronounced in women who never used postmenopausal hormones. This study has limitations because some of the anthropometric information was obtained from retrospective self-reports. Furthermore, data from longitudinal studies with long-term follow-up and repeated anthropometric measures are typically subject to missing data at various time points, which was also the case in this study. Yet, this limitation was partially overcome by using growth curve models, which enabled us to impute data at missing time points for each participant.ConclusionsIn summary, this study showed that a longer duration of overweight and obesity is associated with an increased risk of developing several forms of cancer. Furthermore, the degree of overweight experienced during adulthood seemed to play an important role in the risk of developing cancer, especially for endometrial cancer. Although the observational nature of our study precludes inferring causality or making clinical recommendations, our findings suggest that reducing overweight duration in adulthood could reduce cancer risk and that obesity prevention is important from early onset. If this is true, health care teams should recognize the potential of obesity management in cancer prevention and that excess body weight in women is important to manage regardless of the age of the patient.

Published
2016

22. Physical Functioning Among Women Aged 80 Years and Older With Previous Fracture

Author

Crandall, Carolyn J, LaMonte, Michael J, Snively, Beverly M, LeBoff, Meryl S, Cauley, Jane A, Lewis, Cora E, Wallace, Robert, Li, Wenjun, Chen, Zhao, Robbins, John A, and Wactawski-Wende, Jean

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Health Sciences, Osteoporosis, Aging, Physical Injury - Accidents and Adverse Effects, Rehabilitation, Prevention, Clinical Research, Injuries and accidents, Good Health and Well Being, Aged, 80 and over, Disability Evaluation, Female, Fractures, Bone, Frail Elderly, Geriatric Assessment, Health Status, Health Surveys, Humans, Quality of Life, Survivors, United States, Women's Health, Frailty, Fracture, Physical function, Gerontology, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundThe oldest old are the fastest growing segment of the elderly population. Little is known regarding the associations of fracture history with physical functioning assessed after age 80.MethodsAmong 33,386 women surviving to age 80 years (mean ± SD years 84.6 ± 3.4), we examined the relationship between history of incident fracture after entry into the Women's Health Initiative (follow-up 15.2 ± 1.3 years) and their physical functioning assessed using the RAND-36 instrument most proximal to 2012 end of follow-up.ResultsBaseline mean (±SD) physical function score was 82 (± 18). After adjustment for demographic and medical characteristics, fracture at each site, including hip, upper limb, lower limb, and central body, was associated with significantly lower subsequent physical functioning (all p < .001). Hip, upper leg, spine, and pelvis fractures were particularly related with lower physical functioning scores, 11.7 (95% CI: 10.3, 13.1), 10.5 (8.8, 12.3), 9.8 (8.9, 10.8), and 8.7 (7.2, 10.2) units lower, respectively, compared with women without fracture (each p < .0001). Compared with women without central site fracture, women with central site fractures also had lower physical functioning scores (10.0 [9.3, 10.8] units lower]; p < .0001). In case-only analysis of fractures, older age, less than 1 year since fracture, one or more additional sites fractured, history of cardiovascular disease or cancer, higher body mass index, and no alcohol intake in the past 3 months also were independent predictors of lower physical functioning score (all p < .05).ConclusionsAmong women surviving to 80 years and older, prior fracture is associated with lower current physical functioning, regardless of anatomical site of fracture, independent of other major predictors of disability.

Published
2016

23. Genetic Variants Associated With Quantitative Glucose Homeostasis Traits Translate to Type 2 Diabetes in Mexican Americans: The GUARDIAN (Genetics Underlying Diabetes in Hispanics) Consortium

Author

Palmer, Nicholette D, Goodarzi, Mark O, Langefeld, Carl D, Wang, Nan, Guo, Xiuqing, Taylor, Kent D, Fingerlin, Tasha E, Norris, Jill M, Buchanan, Thomas A, Xiang, Anny H, Haritunians, Talin, Ziegler, Julie T, Williams, Adrienne H, Stefanovski, Darko, Cui, Jinrui, Mackay, Adrienne W, Henkin, Leora F, Bergman, Richard N, Gao, Xiaoyi, Gauderman, James, Varma, Rohit, Hanis, Craig L, Cox, Nancy J, Highland, Heather M, Below, Jennifer E, Williams, Amy L, Burtt, Noel P, Aguilar-Salinas, Carlos A, Huerta-Chagoya, Alicia, Gonzalez-Villalpando, Clicerio, Orozco, Lorena, Haiman, Christopher A, Tsai, Michael Y, Johnson, W Craig, Yao, Jie, Rasmussen-Torvik, Laura, Pankow, James, Snively, Beverly, Jackson, Rebecca D, Liu, Simin, Nadler, Jerry L, Kandeel, Fouad, Chen, Yii-Der I, Bowden, Donald W, Rich, Stephen S, Raffel, Leslie J, Rotter, Jerome I, Watanabe, Richard M, and Wagenknecht, Lynne E

Subjects
Biomedical and Clinical Sciences, Clinical Research, Obesity, Genetics, Diabetes, Human Genome, 2.1 Biological and endogenous factors, Metabolic and endocrine, Blood Glucose, Databases, Factual, Diabetes Mellitus, Type 2, Gene Expression Regulation, Genetic Variation, Genome, Genome-Wide Association Study, Genotype, Hispanic or Latino, Homeostasis, Humans, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences
Abstract

Insulin sensitivity, insulin secretion, insulin clearance, and glucose effectiveness exhibit strong genetic components, although few studies have examined their genetic architecture or influence on type 2 diabetes (T2D) risk. We hypothesized that loci affecting variation in these quantitative traits influence T2D. We completed a multicohort genome-wide association study to search for loci influencing T2D-related quantitative traits in 4,176 Mexican Americans. Quantitative traits were measured by the frequently sampled intravenous glucose tolerance test (four cohorts) or euglycemic clamp (three cohorts), and random-effects models were used to test the association between loci and quantitative traits, adjusting for age, sex, and admixture proportions (Discovery). Analysis revealed a significant (P < 5.00 × 10(-8)) association at 11q14.3 (MTNR1B) with acute insulin response. Loci with P < 0.0001 among the quantitative traits were examined for translation to T2D risk in 6,463 T2D case and 9,232 control subjects of Mexican ancestry (Translation). Nonparametric meta-analysis of the Discovery and Translation cohorts identified significant associations at 6p24 (SLC35B3/TFAP2A) with glucose effectiveness/T2D, 11p15 (KCNQ1) with disposition index/T2D, and 6p22 (CDKAL1) and 11q14 (MTNR1B) with acute insulin response/T2D. These results suggest that T2D and insulin secretion and sensitivity have both shared and distinct genetic factors, potentially delineating genomic components of these quantitative traits that drive the risk for T2D.

Published
2015

24. Whole Genome Sequencing Identifies CRISPLD2 as a Lung Function Gene in Children With Asthma

Author

Abe, Namiko, Abecasis, Goncalo, Albert, Christine, Palmer Allred, Nicholette (Nichole), Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Deborah, Arking, Dan, Arnett, Donna K., Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Barnard, John, Barnes, Kathleen, Barr, R. Graham, Barron-Casella, Emily, Beaty, Terri, Becker, Diane, Becker, Lewis, Beer, Rebecca, Begum, Ferdouse, Beitelshees, Amber, Benjamin, Emelia, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Boerwinkle, Eric, Borecki, Ingrid, Bowler, Russell, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Bunting, Karen, Burchard, Esteban, Cardwell, Jonathan, Carty, Cara, Casaburi, Richard, Casella, James, Chaffin, Mark, Chang, Christy, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Chen, Yii-Der Ida, Cho, Michael H., Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L. Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, Das, Sayantan, David, Sean, Davis, Colleen, Daya, Michelle, de Andrade, Mariza, DeBaun, Michael, Deka, Ranjan, DeMeo, Dawn, Devine, Scott, Do, Ron, Duan, Qing, Duggirala, Ravi, Durda, Peter, Dutcher, Susan, Eaton, Charles, Ekunwe, Lynette, Ellinor, Patrick, Emery, Leslie, Farber, Charles, Farnam, Leanna, Fingerlin, Tasha, Flickinger, Matthew, Fornage, Myriam, Franceschini, Nora, Fu, Mao, Fullerton, Stephanie M., Fulton, Lucinda, Gabriel, Stacey, Gan, Weiniu, Gao, Yan, Gass, Margery, Gelb, Bruce, Geng, Xiaoqi (Priscilla), Germer, Soren, Gignoux, Chris, Gladwin, Mark, Glahn, David, Gogarten, Stephanie, Gong, Da-Wei, Goring, Harald, Gu, C. Charles, Guan, Yue, Guo, Xiuqing, Haessler, Jeff, Hall, Michael, Harris, Daniel, Hawley, Nicola, He, Jiang, Heavner, Ben, Heckbert, Susan, Hernandez, Ryan, Herrington, David, Hersh, Craig, Hidalgo, Bertha, Hixson, James, Hokanson, John, Holly, Kramer, Hong, Elliott, Hoth, Karin, (Agnes) Hsiung, Chao, Huston, Haley, Hwu, Chii Min, Irvin, Marguerite Ryan, Jackson, Rebecca, Jain, Deepti, Jaquish, Cashell, Jhun, Min A., Johnsen, Jill, Johnson, Andrew, Johnson, Craig, Johnston, Rich, Jones, Kimberly, Kachroo, Priyadarshini, Kang, Hyun Min, Kaplan, Robert, Kardia, Sharon, Kathiresan, Sekar, Kaufman, Laura, Kelly, Shannon, Kenny, Eimear, Kessler, Michael, Khan, Alyna, Kinney, Greg, Konkle, Barbara, Kooperberg, Charles, Krauter, Stephanie, Lange, Christoph, Lange, Ethan, Lange, Leslie, Laurie, Cathy, Laurie, Cecelia, LeBoff, Meryl, Lee, Seunggeun Shawn, Lee, Wen-Jane, LeFaive, Jonathon, Levine, David, Levy, Dan, Lewis, Joshua, Li, Yun, Lin, Honghuang, Lin, Keng Han, Liu, Simin, Liu, Yongmei, Loos, Ruth, Lubitz, Steven, Lunetta, Kathryn, Luo, James, Mahaney, Michael, Make, Barry, Manichaikul, Ani, Manson, JoAnn, Margolin, Lauren, Martin, Lisa, Mathai, Susan, Mathias, Rasika, McArdle, Patrick, McDonald, Merry-Lynn, McFarland, Sean, McGarvey, Stephen, Mei, Hao, Meyers, Deborah A., Mikulla, Julie, Min, Nancy, Minear, Mollie, Minster, Ryan L., Mitchell, Braxton, Montasser, May E., Musani, Solomon, Mwasongwe, Stanford, Mychaleckyj, Josyf C., Nadkarni, Girish, Naik, Rakhi, Natarajan, Pradeep, Nekhai, Sergei, Nickerson, Deborah, North, Kari, O'Connell, Jeff, O'Connor, Tim, Ochs-Balcom, Heather, Pankow, James, Papanicolaou, George, Parker, Margaret, Parsa, Afshin, Penchev, Sara, Peralta, Juan Manuel, Perez, Marco, Perry, James, Peters, Ulrike, Peyser, Patricia, Phillips, Lawrence S., Phillips, Sam, Pollin, Toni, Post, Wendy, Becker, Julia Powers, Boorgula, Meher Preethi, Preuss, Michael, Prokopenko, Dmitry, Psaty, Bruce, Qasba, Pankaj, Qiao, Dandi, Qin, Zhaohui, Rafaels, Nicholas, Raffield, Laura, Ramachandran, Vasan, Rao, D.C., Rasmussen-Torvik, Laura, Ratan, Aakrosh, Redline, Susan, Reed, Robert, Regan, Elizabeth, Reiner, Alex, Rice, Ken, Rich, Stephen, Roden, Dan, Roselli, Carolina, Rotter, Jerome, Ruczinski, Ingo, Russell, Pamela, Ruuska, Sarah, Ryan, Kathleen, Sakornsakolpat, Phuwanat, Salimi, Shabnam, Salzberg, Steven, Sandow, Kevin, Sankaran, Vijay, Scheller, Christopher, Schmidt, Ellen, Schwander, Karen, Schwartz, David, Sciurba, Frank, Seidman, Christine, Seidman, Jonathan, Sheehan, Vivien, Shetty, Amol, Shetty, Aniket, Sheu, Wayne Hui-Heng, Shoemaker, M. Benjamin, Silver, Brian, Silverman, Edwin, Smith, Jennifer, Smith, Josh, Smith, Nicholas, Smith, Tanja, Smoller, Sylvia, Snively, Beverly, Sofer, Tamar, Sotoodehnia, Nona, Stilp, Adrienne, Streeten, Elizabeth, Sung, Yun Ju, Su-Lasky, Jessica, Sylvia, Jody, Szpiro, Adam, Sztalryd, Carole, Taliun, Daniel, Tang, Hua, Taub, Margaret, Taylor, Kent, Taylor, Simeon, Telen, Marilyn, Thornton, Timothy A., Tinker, Lesley, Tirschwell, David, Tiwari, Hemant, Tracy, Russell, Tsai, Michael, Vaidya, Dhananjay, VandeHaar, Peter, Vrieze, Scott, Walker, Tarik, Wallace, Robert, Walts, Avram, Wan, Emily, Wang, Fei Fei, Watson, Karol, Weeks, Daniel E., Weir, Bruce, Weiss, Scott, Weng, Lu-Chen, Willer, Cristen, Williams, Kayleen, Williams, L. Keoki, Wilson, Carla, Wilson, James, Wong, Quenna, Xu, Huichun, Yanek, Lisa, Yang, Ivana, Yang, Rongze, Zaghloul, Norann, Zekavat, Maryam, Zhang, Yingze, Zhao, Snow Xueyan, Zhao, Wei, Zheng, Xiuwen, Zhi, Degui, Zhou, Xiang, Zody, Michael, Zoellner, Sebastian, Hecker, Julian, Chawes, Bo L., Ahluwalia, Tarunveer S., Kelly, Rachel S., Chu, Su H., Virkud, Yamini V., Huang, Mengna, Barnes, Kathleen C., Burchard, Esteban G., Eng, Celeste, Hu, Donglei, Celedón, Juan C., Levin, Albert M., Gui, Hongsheng, Forno, Erick, Mak, Angel C.Y., Avila, Lydiana, Soto-Quiros, Manuel E., Cloutier, Michelle M., Acosta-Pérez, Edna, Canino, Glorisa, Bønnelykke, Klaus, Bisgaard, Hans, Raby, Benjamin A., Weiss, Scott T., and Lasky-Su, Jessica A.

Published
2019
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26. Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes.

Author

Ng, Maggie CY, Shriner, Daniel, Chen, Brian H, Li, Jiang, Chen, Wei-Min, Guo, Xiuqing, Liu, Jiankang, Bielinski, Suzette J, Yanek, Lisa R, Nalls, Michael A, Comeau, Mary E, Rasmussen-Torvik, Laura J, Jensen, Richard A, Evans, Daniel S, Sun, Yan V, An, Ping, Patel, Sanjay R, Lu, Yingchang, Long, Jirong, Armstrong, Loren L, Wagenknecht, Lynne, Yang, Lingyao, Snively, Beverly M, Palmer, Nicholette D, Mudgal, Poorva, Langefeld, Carl D, Keene, Keith L, Freedman, Barry I, Mychaleckyj, Josyf C, Nayak, Uma, Raffel, Leslie J, Goodarzi, Mark O, Chen, Y-D Ida, Taylor, Herman A, Correa, Adolfo, Sims, Mario, Couper, David, Pankow, James S, Boerwinkle, Eric, Adeyemo, Adebowale, Doumatey, Ayo, Chen, Guanjie, Mathias, Rasika A, Vaidya, Dhananjay, Singleton, Andrew B, Zonderman, Alan B, Igo, Robert P, Sedor, John R, FIND Consortium, Kabagambe, Edmond K, Siscovick, David S, McKnight, Barbara, Rice, Kenneth, Liu, Yongmei, Hsueh, Wen-Chi, Zhao, Wei, Bielak, Lawrence F, Kraja, Aldi, Province, Michael A, Bottinger, Erwin P, Gottesman, Omri, Cai, Qiuyin, Zheng, Wei, Blot, William J, Lowe, William L, Pacheco, Jennifer A, Crawford, Dana C, eMERGE Consortium, DIAGRAM Consortium, Grundberg, Elin, MuTHER Consortium, Rich, Stephen S, Hayes, M Geoffrey, Shu, Xiao-Ou, Loos, Ruth JF, Borecki, Ingrid B, Peyser, Patricia A, Cummings, Steven R, Psaty, Bruce M, Fornage, Myriam, Iyengar, Sudha K, Evans, Michele K, Becker, Diane M, Kao, WH Linda, Wilson, James G, Rotter, Jerome I, Sale, Michèle M, Liu, Simin, Rotimi, Charles N, Bowden, Donald W, and MEta-analysis of type 2 DIabetes in African Americans Consortium

Subjects
FIND Consortium, eMERGE Consortium, DIAGRAM Consortium, MuTHER Consortium, MEta-analysis of type 2 DIabetes in African Americans Consortium, Humans, Diabetes Mellitus, Type 2, HMGA2 Protein, HLA-B27 Antigen, Polymorphism, Single Nucleotide, African Americans, Mutant Chimeric Proteins, KCNQ1 Potassium Channel, Genome-Wide Association Study, Transcription Factor 7-Like 2 Protein, Human Genome, Diabetes, Genetics, 2.1 Biological and endogenous factors, Metabolic and endocrine, Developmental Biology
Abstract

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)

Published
2014

28. Associations between Single Nucleotide Polymorphisms in Iron-Related Genes and Iron Status in Multiethnic Populations

Author

McLaren, Christine E., McLachlan, Stela, Garner, Chad P., Vulpe, Chris D., Gordeuk, Victor R., Eckfeldt, John H., Adams, Paul C., Acton, Ronald T., Murray, Joseph A., Leiendecker-Foster, Catherine, Snively, Beverly M., Barcellos, Lisa F., Cook, James D., and McLaren, Gordon D.

Abstract

The existence of multiple inherited disorders of iron metabolism suggests genetic contributions to iron deficiency. We previously performed a genome-wide association study of iron-related single nucleotide polymorphisms (SNPs) using DNA from white men aged ≥25 y and women ≥50 y in the Hemochromatosis and Iron Overload Screening (HEIRS) Study with serum ferritin (SF) ≤12 µg/L (cases) and controls (SF >100 µg/L in men, SF >50 µg/L in women). We report a follow-up study of white, African-American, Hispanic, and Asian HEIRS participants, analyzed for association between SNPs and eight iron-related outcomes. Three chromosomal regions showed association across multiple populations, including SNPs in the TF and TMPRSS6 genes, and on chromosome 18q21. A novel SNP rs1421312 in TMPRSS6 was associated with serum iron in whites (p = 3.7×10−6) and replicated in African Americans (p = 0.0012).Twenty SNPs in the TF gene region were associated with total iron-binding capacity in whites (p

Published
2012

29. A meta-analysis and genome-wide association study of platelet count and mean platelet volume in african americans.

Author

Qayyum, Rehan, Snively, Beverly M, Ziv, Elad, Nalls, Michael A, Liu, Yongmei, Tang, Weihong, Yanek, Lisa R, Lange, Leslie, Evans, Michele K, Ganesh, Santhi, Austin, Melissa A, Lettre, Guillaume, Becker, Diane M, Zonderman, Alan B, Singleton, Andrew B, Harris, Tamara B, Mohler, Emile R, Logsdon, Benjamin A, Kooperberg, Charles, Folsom, Aaron R, Wilson, James G, Becker, Lewis C, and Reiner, Alexander P

Subjects
Blood Platelets, Humans, Platelet Count, Platelet Aggregation, Genotype, Polymorphism, Single Nucleotide, Adult, Aged, Middle Aged, African Americans, Female, Male, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Genetics, Developmental Biology
Abstract

Several genetic variants associated with platelet count and mean platelet volume (MPV) were recently reported in people of European ancestry. In this meta-analysis of 7 genome-wide association studies (GWAS) enrolling African Americans, our aim was to identify novel genetic variants associated with platelet count and MPV. For all cohorts, GWAS analysis was performed using additive models after adjusting for age, sex, and population stratification. For both platelet phenotypes, meta-analyses were conducted using inverse-variance weighted fixed-effect models. Platelet aggregation assays in whole blood were performed in the participants of the GeneSTAR cohort. Genetic variants in ten independent regions were associated with platelet count (N = 16,388) with p

Published
2012

30. Genome-wide association study of white blood cell count in 16,388 African Americans: the continental origins and genetic epidemiology network (COGENT).

Author

Reiner, Alexander P, Lettre, Guillaume, Nalls, Michael A, Ganesh, Santhi K, Mathias, Rasika, Austin, Melissa A, Dean, Eric, Arepalli, Sampath, Britton, Angela, Chen, Zhao, Couper, David, Curb, J David, Eaton, Charles B, Fornage, Myriam, Grant, Struan FA, Harris, Tamara B, Hernandez, Dena, Kamatini, Naoyuki, Keating, Brendan J, Kubo, Michiaki, LaCroix, Andrea, Lange, Leslie A, Liu, Simin, Lohman, Kurt, Meng, Yan, Mohler, Emile R, Musani, Solomon, Nakamura, Yusuke, O'Donnell, Christopher J, Okada, Yukinori, Palmer, Cameron D, Papanicolaou, George J, Patel, Kushang V, Singleton, Andrew B, Takahashi, Atsushi, Tang, Hua, Taylor, Herman A, Taylor, Kent, Thomson, Cynthia, Yanek, Lisa R, Yang, Lingyao, Ziv, Elad, Zonderman, Alan B, Folsom, Aaron R, Evans, Michele K, Liu, Yongmei, Becker, Diane M, Snively, Beverly M, and Wilson, James G

Subjects
Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 4, Chromosomes, Human, Pair 16, Humans, Microfilament Proteins, Receptors, Cell Surface, Duffy Blood-Group System, Leukocyte Count, Artifacts, Reproducibility of Results, DNA Replication, Phenotype, Polymorphism, Single Nucleotide, African Americans, Asian Continental Ancestry Group, European Continental Ancestry Group, Chemokine CXCL2, Genome-Wide Association Study, Molecular Epidemiology, Genetic Loci, Chromosomes, Human, Pair 1, Pair 4, Pair 16, Receptors, Cell Surface, Polymorphism, Single Nucleotide, Genetics, Developmental Biology
Abstract

Total white blood cell (WBC) and neutrophil counts are lower among individuals of African descent due to the common African-derived "null" variant of the Duffy Antigen Receptor for Chemokines (DARC) gene. Additional common genetic polymorphisms were recently associated with total WBC and WBC sub-type levels in European and Japanese populations. No additional loci that account for WBC variability have been identified in African Americans. In order to address this, we performed a large genome-wide association study (GWAS) of total WBC and cell subtype counts in 16,388 African-American participants from 7 population-based cohorts available in the Continental Origins and Genetic Epidemiology Network. In addition to the DARC locus on chromosome 1q23, we identified two other regions (chromosomes 4q13 and 16q22) associated with WBC in African Americans (P

Published
2011

31. Genome-Wide Association Study Identifies Genetic Loci Associated with Iron Deficiency

Author

McLaren, Christine E., Garner, Chad P., Constantine, Clare C., McLachlan, Stela, Vulpe, Chris D., Snively, Beverly M., Gordeuk, Victor R., Nickerson, Debbie A., Cook, James D., Leiendecker-Foster, Catherine, Beckman, Kenneth B., Eckfeldt, John H., Barcellos, Lisa F., Murray, Joseph A., Adams, Paul C., Acton, Ronald T., Killeen, Anthony A., and McLaren, Gordon D.

Subjects
overload screening heirs, serum ferritin, transferrin saturation, hfe hemochromatosis, binding-capacity, common variants, g277s mutation, tmprss6 gene, metabolism, anemia
Abstract

The existence of multiple inherited disorders of iron metabolism in man, rodents and other vertebrates suggests genetic contributions to iron deficiency. To identify new genomic locations associated with iron deficiency, a genome-wide association study (GWAS) was performed using DNA collected from white men aged ≥25 y and women ≥50 y in the Hemochromatosis and Iron Overload Screening (HEIRS) Study with serum ferritin (SF) ≤ 12 µg/L (cases) and iron replete controls (SF>100 µg/L in men, SF>50 µg/L in women). Regression analysis was used to examine the association between case-control status (336 cases, 343 controls) and quantitative serum iron measures and 331,060 single nucleotide polymorphism (SNP) genotypes, with replication analyses performed in a sample of 71 cases and 161 controls from a population of white male and female veterans screened at a US Veterans Affairs (VA) medical center. Five SNPs identified in the GWAS met genome-wide statistical significance for association with at least one iron measure, rs2698530 on chr. 2p14; rs3811647 on chr. 3q22, a known SNP in the transferrin (TF) gene region; rs1800562 on chr. 6p22, the C282Y mutation in the HFE gene; rs7787204 on chr. 7p21; and rs987710 on chr. 22q11 (GWAS observed P

Published
2011

34. Type 2 Diabetes Variants Disrupt Function of SLC16A11 through Two Distinct Mechanisms

Author

Ng, Maggie C.Y., Shriner, Daniel, Chen, Brian H., Li, Jiang, Chen, Wei-Min, Guo, Xiuqing, Liu, Jiankang, Bielinski, Suzette J., Yanek, Lisa R., Nalls, Michael A., Comeau, Mary E., Rasmussen-Torvik, Laura J., Jensen, Richard A., Evans, Daniel S., Sun, Yan V., An, Ping, Patel, Sanjay R., Lu, Yingchang, Long, Jirong, Armstrong, Loren L., Wagenknecht, Lynne, Yang, Lingyao, Snively, Beverly M., Palmer, Nicholette D., Mudgal, Poorva, Langefeld, Carl D., Keene, Keith L., Freedman, Barry I., Mychaleckyj, Josyf C., Nayak, Uma, Raffel, Leslie J., Goodarzi, Mark O., Chen, Y-D Ida, Taylor, Herman A., Jr., Correa, Adolfo, Sims, Mario, Couper, David, Pankow, James S., Boerwinkle, Eric, Adeyemo, Adebowale, Doumatey, Ayo, Chen, Guanjie, Mathias, Rasika A., Vaidya, Dhananjay, Singleton, Andrew B., Zonderman, Alan B., Igo, Robert P., Jr., Sedor, John R., Kabagambe, Edmond K., Siscovick, David S., McKnight, Barbara, Rice, Kenneth, Liu, Yongmei, Hsueh, Wen-Chi, Zhao, Wei, Bielak, Lawrence F., Kraja, Aldi, Province, Michael A., Bottinger, Erwin P., Gottesman, Omri, Cai, Qiuyin, Zheng, Wei, Blot, William J., Lowe, William L., Pacheco, Jennifer A., Crawford, Dana C., Grundberg, Elin, Rich, Stephen S., Hayes, M. Geoffrey, Shu, Xiao-Ou, Loos, Ruth J.F., Borecki, Ingrid B., Peyser, Patricia A., Cummings, Steven R., Psaty, Bruce M., Fornage, Myriam, Iyengar, Sudha K., Evans, Michele K., Becker, Diane M., Kao, W.H. Linda, Wilson, James G., Rotter, Jerome I., Sale, Michèle M., Liu, Simin, Rotimi, Charles N., Bowden, Donald W., Mercader, Josep M., Huerta-Chagoya, Alicia, García-Ortiz, Humberto, Moreno-Macías, Hortensia, Manning, Alisa, Caulkins, Lizz, Burtt, Noël P., Flannick, Jason, Patterson, Nick, Aguilar-Salinas, Carlos A., Tusié-Luna, Teresa, Altshuler, David, Florez, Jose C., Martínez-Hernández, Angélica, Centeno-Cruz, Federico, Barajas-Olmos, Francisco Martin, Zerrweck, Carlos, Contreras-Cubas, Cecilia, Mendoza-Caamal, Elvia, Revilla-Monsalve, Cristina, Islas-Andrade, Sergio, Córdova, Emilio, Soberón, Xavier, Orozco, Lorena, González-Villalpando, Clicerio, González-Villalpando, María Elena, Haiman, Christopher A., Wilkens, Lynne, Le Marchand, Loic, Monroe, Kristine, Kolonel, Laurence, Arellano-Campos, Olimpia, Ordóñez-Sánchez, Maria L., Rodríguez-Torres, Maribel, Segura-Kato, Yayoi, Rodríguez-Guillén, Rosario, Cruz-Bautista, Ivette, Muñoz-Hernandez, Linda Liliana, Sáenz, Tamara, Gómez, Donají, Alvirde, Ulices, Almeda-Valdés, Paloma, Cortes, Maria L., Rusu, Victor, Hoch, Eitan, Tenen, Danielle E., Gymrek, Melissa, Hartigan, Christina R., DeRan, Michael, von Grotthuss, Marcin, Fontanillas, Pierre, Spooner, Alexandra, Guzman, Gaelen, Deik, Amy A., Pierce, Kerry A., Dennis, Courtney, Clish, Clary B., Carr, Steven A., Wagner, Bridget K., Schenone, Monica, Altshuler, David M., Schreiber, Stuart L., Jacobs, Suzanne B.R., and Lander, Eric S.

Published
2017
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35. Hemochromatosis and Iron-Overload Screening in a Racially Diverse Population

Author

Adams, Paul C, Reboussin, David M, Barton, James C, McLaren, Christine E, Eckfeldt, John H, McLaren, Gordon D, Dawkins, Fitzroy W, Acton, Ronald T, Harris, Emily L, Gordeuk, Victor R, Leiendecker-Foster, Catherine, Speechley, Mark, Snively, Beverly M, Holup, Joan L, Thomson, Elizabeth, and Sholinsky, Phyliss

Subjects
Health Services and Systems, Health Sciences, Liver Disease, Minority Health, Hematology, Chronic Liver Disease and Cirrhosis, Digestive Diseases, Genetics, Arthritis, Diabetes Complications, Female, Ferritins, Gene Frequency, Genotype, Heart Diseases, Hemochromatosis, Hemochromatosis Protein, Histocompatibility Antigens Class I, Homozygote, Humans, Iron, Iron Overload, Liver Diseases, Logistic Models, Male, Membrane Proteins, Mutation, Phenotype, Sex Distribution, Transferrin, United States, Hemochromatosis and Iron Overload Screening (HEIRS) Study Research Investigators, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundIron overload and hemochromatosis are common, treatable conditions. HFE genotypes, levels of serum ferritin, transferrin saturation values, and self-reported medical history were studied in a multiethnic primary care population.MethodsParticipants were recruited from primary care practices and blood-drawing laboratories. Blood samples were tested for transferrin saturation, serum ferritin, and C282Y and H63D mutations of the HFE gene. Before genetic screening, participants were asked whether they had a history of medical conditions related to iron overload.ResultsOf the 99,711 participants, 299 were homozygous for the C282Y mutation. The estimated prevalence of C282Y homozygotes was higher in non-Hispanic whites (0.44 percent) than in Native Americans (0.11 percent), Hispanics (0.027 percent), blacks (0.014 percent), Pacific Islanders (0.012 percent), or Asians (0.000039 percent). Among participants who were homozygous for the C282Y mutation but in whom iron overload had not been diagnosed (227 participants), serum ferritin levels were greater than 300 mug per liter in 78 of 89 men (88 percent) and greater than 200 microg per liter in 79 of 138 women (57 percent). Pacific Islanders and Asians had the highest geometric mean levels of serum ferritin and mean transferrin saturation despite having the lowest prevalence of C282Y homozygotes. There were 364 participants in whom iron overload had not been diagnosed (29 C282Y homozygotes) who had a serum ferritin level greater than 1000 microg per liter. Among men, C282Y homozygotes and compound heterozygotes were more likely to report a history of liver disease than were participants without HFE mutations.ConclusionsThe C282Y mutation is most common in whites, and most C282Y homozygotes have elevations in serum ferritin levels and transferrin saturation. The C282Y mutation does not account for high mean serum ferritin levels and transferrin saturation values in nonwhites.

Published
2005

37. Epigenome-wide DNA methylation association study of circulating IgE levels identifies novel targets for asthma

Author

Recto, Kathryn, primary, Kachroo, Priyadarshini, additional, Huan, Tianxiao, additional, Van Den Berg, David, additional, Lee, Gha Young, additional, Bui, Helena, additional, Lee, Dong Heon, additional, Gereige, Jessica, additional, Yao, Chen, additional, Hwang, Shih-Jen, additional, Joehanes, Roby, additional, Weiss, Scott T., additional, O’Connor, George T., additional, Levy, Daniel, additional, DeMeo, Dawn L., additional, Abe, Namiko, additional, Abecasis, Gonçalo, additional, Aguet, Francois, additional, Albert, Christine, additional, Almasy, Laura, additional, Alonso, Alvaro, additional, Ament, Seth, additional, Anderson, Peter, additional, Anugu, Pramod, additional, Applebaum-Bowden, Deborah, additional, Ardlie, Kristin, additional, Arking, Dan, additional, Arnett, Donna K., additional, Ashley-Koch, Allison, additional, Aslibekyan, Stella, additional, Assimes, Tim, additional, Auer, Paul, additional, Avramopoulos, Dimitrios, additional, Ayas, Najib, additional, Balasubramanian, Adithya, additional, Barnard, John, additional, Barnes, Kathleen, additional, Barr, R. Graham, additional, Barron-Casella, Emily, additional, Barwick, Lucas, additional, Beaty, Terri, additional, Beck, Gerald, additional, Becker, Diane, additional, Becker, Lewis, additional, Beer, Rebecca, additional, Beitelshees, Amber, additional, Benjamin, Emelia, additional, Benos, Takis, additional, Bezerra, Marcos, additional, Bielak, Larry, additional, Bis, Joshua, additional, Blackwell, Thomas, additional, Blangero, John, additional, Blue, Nathan, additional, Boerwinkle, Eric, additional, Bowden, Donald W., additional, Bowler, Russell, additional, Brody, Jennifer, additional, Broeckel, Ulrich, additional, Broome, Jai, additional, Brown, Deborah, additional, Bunting, Karen, additional, Burchard, Esteban, additional, Bustamante, Carlos, additional, Buth, Erin, additional, Cade, Brian, additional, Cardwell, Jonathan, additional, Carey, Vincent, additional, Carrier, Julie, additional, Carson, April P., additional, Carty, Cara, additional, Casaburi, Richard, additional, Casas Romero, Juan P., additional, Casella, James, additional, Castaldi, Peter, additional, Chaffin, Mark, additional, Chang, Christy, additional, Chang, Yi-Cheng, additional, Chasman, Daniel, additional, Chavan, Sameer, additional, Chen, Bo-Juen, additional, Chen, Wei-Min, additional, Ida Chen, Yii-Der, additional, Cho, Michael, additional, Choi, Seung Hoan, additional, Chuang, Lee-Ming, additional, Chung, Mina, additional, Chung, Ren-Hua, additional, Clish, Clary, additional, Comhair, Suzy, additional, Conomos, Matthew, additional, Cornell, Elaine, additional, Correa, Adolfo, additional, Crandall, Carolyn, additional, Crapo, James, additional, Cupples, L. Adrienne, additional, Curran, Joanne, additional, Curtis, Jeffrey, additional, Custer, Brian, additional, Damcott, Coleen, additional, Darbar, Dawood, additional, David, Sean, additional, Davis, Colleen, additional, Daya, Michelle, additional, de Andrade, Mariza, additional, de las Fuentes, Lisa, additional, de Vries, Paul, additional, DeBaun, Michael, additional, Deka, Ranjan, additional, DeMeo, Dawn, additional, Devine, Scott, additional, Dinh, Huyen, additional, Doddapaneni, Harsha, additional, Duan, Qing, additional, Dugan-Perez, Shannon, additional, Duggirala, Ravi, additional, Durda, Jon Peter, additional, Dutcher, Susan K., additional, Eaton, Charles, additional, Ekunwe, Lynette, additional, El Boueiz, Adel, additional, Ellinor, Patrick, additional, Emery, Leslie, additional, Erzurum, Serpil, additional, Farber, Charles, additional, Farek, Jesse, additional, Fingerlin, Tasha, additional, Flickinger, Matthew, additional, Fornage, Myriam, additional, Franceschini, Nora, additional, Frazar, Chris, additional, Fu, Mao, additional, Fullerton, Stephanie M., additional, Fulton, Lucinda, additional, Gabriel, Stacey, additional, Gan, Weiniu, additional, Gao, Shanshan, additional, Gao, Yan, additional, Gass, Margery, additional, Geiger, Heather, additional, Gelb, Bruce, additional, Geraci, Mark, additional, Germer, Soren, additional, Gerszten, Robert, additional, Ghosh, Auyon, additional, Gibbs, Richard, additional, Gignoux, Chris, additional, Gladwin, Mark, additional, Glahn, David, additional, Gogarten, Stephanie, additional, Gong, Da-Wei, additional, Goring, Harald, additional, Graw, Sharon, additional, Gray, Kathryn J., additional, Grine, Daniel, additional, Gross, Colin, additional, Gu, C. Charles, additional, Guan, Yue, additional, Guo, Xiuqing, additional, Gupta, Namrata, additional, Haessler, Jeff, additional, Hall, Michael, additional, Han, Yi, additional, Hanly, Patrick, additional, Harris, Daniel, additional, Hawley, Nicola L., additional, He, Jiang, additional, Heavner, Ben, additional, Heckbert, Susan, additional, Hernandez, Ryan, additional, Herrington, David, additional, Hersh, Craig, additional, Hidalgo, Bertha, additional, Hixson, James, additional, Hobbs, Brian, additional, Hokanson, John, additional, Hong, Elliott, additional, Hoth, Karin, additional, Hsiung, Chao (Agnes), additional, Hu, Jianhong, additional, Hung, Yi-Jen, additional, Huston, Haley, additional, Hwu, Chii Min, additional, Irvin, Marguerite Ryan, additional, Jackson, Rebecca, additional, Jain, Deepti, additional, Jaquish, Cashell, additional, Johnsen, Jill, additional, Johnson, Andrew, additional, Johnson, Craig, additional, Johnston, Rich, additional, Jones, Kimberly, additional, Kang, Hyun Min, additional, Kaplan, Robert, additional, Kardia, Sharon, additional, Kelly, Shannon, additional, Kenny, Eimear, additional, Kessler, Michael, additional, Khan, Alyna, additional, Khan, Ziad, additional, Kim, Wonji, additional, Kimoff, John, additional, Kinney, Greg, additional, Konkle, Barbara, additional, Kooperberg, Charles, additional, Kramer, Holly, additional, Lange, Christoph, additional, Lange, Ethan, additional, Lange, Leslie, additional, Laurie, Cathy, additional, Laurie, Cecelia, additional, LeBoff, Meryl, additional, Lee, Jiwon, additional, Lee, Sandra, additional, Lee, Wen-Jane, additional, LeFaive, Jonathon, additional, Levine, David, additional, Lewis, Joshua, additional, Li, Xiaohui, additional, Li, Yun, additional, Lin, Henry, additional, Lin, Honghuang, additional, Lin, Xihong, additional, Liu, Simin, additional, Liu, Yongmei, additional, Liu, Yu, additional, Loos, Ruth J.F., additional, Lubitz, Steven, additional, Lunetta, Kathryn, additional, Luo, James, additional, Magalang, Ulysses, additional, Mahaney, Michael, additional, Make, Barry, additional, Manichaikul, Ani, additional, Manning, Alisa, additional, Manson, JoAnn, additional, Martin, Lisa, additional, Marton, Melissa, additional, Mathai, Susan, additional, Mathias, Rasika, additional, May, Susanne, additional, McArdle, Patrick, additional, McDonald, Merry-Lynn, additional, McFarland, Sean, additional, McGarvey, Stephen, additional, McGoldrick, Daniel, additional, McHugh, Caitlin, additional, McNeil, Becky, additional, Mei, Hao, additional, Meigs, James, additional, Menon, Vipin, additional, Mestroni, Luisa, additional, Metcalf, Ginger, additional, Meyers, Deborah A., additional, Mignot, Emmanuel, additional, Mikulla, Julie, additional, Min, Nancy, additional, Minear, Mollie, additional, Minster, Ryan L., additional, Mitchell, Braxton D., additional, Moll, Matt, additional, Momin, Zeineen, additional, Montasser, May E., additional, Montgomery, Courtney, additional, Muzny, Donna, additional, Mychaleckyj, Josyf C., additional, Nadkarni, Girish, additional, Naik, Rakhi, additional, Naseri, Take, additional, Natarajan, Pradeep, additional, Nekhai, Sergei, additional, Nelson, Sarah C., additional, Neltner, Bonnie, additional, Nessner, Caitlin, additional, Nickerson, Deborah, additional, Nkechinyere, Osuji, additional, North, Kari, additional, O'Connell, Jeff, additional, O'Connor, Tim, additional, Ochs-Balcom, Heather, additional, Okwuonu, Geoffrey, additional, Pack, Allan, additional, Paik, David T., additional, Palmer, Nicholette, additional, Pankow, James, additional, Papanicolaou, George, additional, Parker, Cora, additional, Peloso, Gina, additional, Peralta, Juan Manuel, additional, Perez, Marco, additional, Perry, James, additional, Peters, Ulrike, additional, Peyser, Patricia, additional, Phillips, Lawrence S., additional, Pleiness, Jacob, additional, Pollin, Toni, additional, Post, Wendy, additional, Powers Becker, Julia, additional, Preethi Boorgula, Meher, additional, Preuss, Michael, additional, Psaty, Bruce, additional, Qasba, Pankaj, additional, Qiao, Dandi, additional, Qin, Zhaohui, additional, Rafaels, Nicholas, additional, Raffield, Laura, additional, Rajendran, Mahitha, additional, Ramachandran, Vasan S., additional, Rao, D.C., additional, Rasmussen-Torvik, Laura, additional, Ratan, Aakrosh, additional, Redline, Susan, additional, Reed, Robert, additional, Reeves, Catherine, additional, Regan, Elizabeth, additional, Reiner, Alex, additional, Reupena, Muagututi‘a Sefuiva, additional, Rice, Ken, additional, Rich, Stephen, additional, Robillard, Rebecca, additional, Robine, Nicolas, additional, Roden, Dan, additional, Roselli, Carolina, additional, Rotter, Jerome, additional, Ruczinski, Ingo, additional, Runnels, Alexi, additional, Russell, Pamela, additional, Ruuska, Sarah, additional, Ryan, Kathleen, additional, Sabino, Ester Cerdeira, additional, Saleheen, Danish, additional, Salimi, Shabnam, additional, Salvi, Sejal, additional, Salzberg, Steven, additional, Sandow, Kevin, additional, Sankaran, Vijay G., additional, Santibanez, Jireh, additional, Schwander, Karen, additional, Schwartz, David, additional, Sciurba, Frank, additional, Seidman, Christine, additional, Seidman, Jonathan, additional, Sériès, Frédéric, additional, Sheehan, Vivien, additional, Sherman, Stephanie L., additional, Shetty, Amol, additional, Shetty, Aniket, additional, Sheu, Wayne Hui-Heng, additional, Shoemaker, M. Benjamin, additional, Silver, Brian, additional, Silverman, Edwin, additional, Skomro, Robert, additional, Smith, Albert Vernon, additional, Smith, Jennifer, additional, Smith, Josh, additional, Smith, Nicholas, additional, Smith, Tanja, additional, Smoller, Sylvia, additional, Snively, Beverly, additional, Snyder, Michael, additional, Sofer, Tamar, additional, Sotoodehnia, Nona, additional, Stilp, Adrienne M., additional, Storm, Garrett, additional, Streeten, Elizabeth, additional, Su, Jessica Lasky, additional, Sung, Yun Ju, additional, Sylvia, Jody, additional, Szpiro, Adam, additional, Taliun, Daniel, additional, Tang, Hua, additional, Taub, Margaret, additional, Taylor, Kent, additional, Taylor, Matthew, additional, Taylor, Simeon, additional, Telen, Marilyn, additional, Thornton, Timothy A., additional, Threlkeld, Machiko, additional, Tinker, Lesley, additional, Tirschwell, David, additional, Tishkoff, Sarah, additional, Tiwari, Hemant, additional, Tong, Catherine, additional, Tracy, Russell, additional, Tsai, Michael, additional, Vaidya, Dhananjay, additional, VandeHaar, Peter, additional, Vrieze, Scott, additional, Walker, Tarik, additional, Wallace, Robert, additional, Walts, Avram, additional, Wang, Fei Fei, additional, Wang, Heming, additional, Wang, Jiongming, additional, Watson, Karol, additional, Watt, Jennifer, additional, Weeks, Daniel E., additional, Weinstock, Joshua, additional, Weir, Bruce, additional, Weng, Lu-Chen, additional, Wessel, Jennifer, additional, Willer, Cristen, additional, Williams, Kayleen, additional, Williams, L. Keoki, additional, Williams, Scott, additional, Wilson, Carla, additional, Wilson, James, additional, Winterkorn, Lara, additional, Wong, Quenna, additional, Wu, Baojun, additional, Wu, Joseph, additional, Xu, Huichun, additional, Yanek, Lisa, additional, Yang, Ivana, additional, Yu, Ketian, additional, Zekavat, Seyedeh Maryam, additional, Zhang, Yingze, additional, Zhao, Snow Xueyan, additional, Zhao, Wei, additional, Zhu, Xiaofeng, additional, Ziv, Elad, additional, Zody, Michael, additional, and Zoellner, Sebastian, additional

Published
2023
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38. Collaborative Care to Improve Quality of Life for Anxiety and Depression in Posttraumatic Epilepsy (CoCarePTE): Protocol for a Randomized Hybrid Effectiveness-Implementation Trial.

Author

Munger Clary, Heidi M, Snively, Beverly M, Cagle, Christian, Kennerly, Richard, Kimball, James N, Alexander, Halley B, Brenes, Gretchen A, Moore, Justin B, and Hurley, Robin A

Subjects
ANXIETY, MENTAL depression, QUALITY of life, POST-traumatic stress, MENTAL health
Abstract

Background: Anxiety and depression in people with epilepsy are common and associated with poor outcomes; yet, they often go untreated due to poor mental health specialist access. Collaborative care is an integrated care model with a strong evidence base in primary care and medical settings, but it has not been evaluated in neurology clinics. Evaluating implementation outcomes when translating evidence-based interventions to new clinical settings to inform future scaling and incorporation into real-world practice is important. Objective: The Collaborative Care for Posttraumatic Epilepsy (CoCarePTE) trial aims to evaluate the effectiveness (improvement in emotional quality of life) and implementation of a collaborative care intervention for people with anxiety or depressive symptoms and posttraumatic epilepsy. Methods: CoCarePTE is a 2-site, randomized, single-blind, hybrid type 1 effectiveness-implementation trial that will randomize 60 adults to receive either neurology-based collaborative care or usual care. Adults receiving neurological care at participating centers with anxiety or depressive symptoms and a history of at least mild traumatic brain injury before epilepsy onset will be enrolled. The collaborative care intervention is a 24-week stepped-care model with video or telephone calls every 2 weeks by a care manager for measurement-based anxiety and depression care, seizure care monitoring, and brief therapy intervention delivery. This is supplemented by antidepressant prescribing recommendations by psychiatrists for neurologists via case conferences and care manager–facilitated team communication. In step 2 of the intervention, individuals with <50% symptom reduction by 10 weeks will receive an added 8-session remote cognitive behavioral therapy program. The study is powered to detect a moderate improvement in emotional quality of life. As a hybrid type 1 trial, effectiveness is the primary focus, with the primary outcome being a change in emotional quality of life at 6 months in the intervention group compared to control. Secondary effectiveness outcomes are 6-month changes in depression, anxiety, and overall quality of life. Implementation outcomes, including fidelity, acceptability, feasibility, and appropriateness, are evaluated before implementation and at 3 months. The primary effectiveness analysis will compare changes in emotional quality of life scores from baseline to 6 months between the intervention and control arms using multiple linear regression modeling, adjusting for study site and using an intent-to-treat approach. Results: Enrollment commenced in 2023, with modifications in the inclusion and exclusion made after the first 6 enrollees due to slow recruitment. Enrollment is expected to continue at least into early 2025. Conclusions: The CoCarePTE trial is novel in its use of a hybrid effectiveness-implementation design to evaluate an evidence-based mental health intervention in epilepsy, and by incorporating seizure care into a collaborative care model. If a significant improvement in emotional quality of life is found in the intervention group compared to usual care, this would support next step scaling or clinical implementation. Trial Registration: ClinicalTrials.gov NCT05353452; https://www.clinicaltrials.gov/study/NCT05353452 International Registered Report Identifier (IRRID): DERR1-10.2196/59329 [ABSTRACT FROM AUTHOR]

Published
2024
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44. An APOO Pseudogene on Chromosome 5q Is Associated With Low-Density Lipoprotein Cholesterol Levels

Author

Montasser, May E., O’Hare, Elizabeth A., Wang, Xiaochun, Howard, Alicia D., McFarland, Rebecca, Perry, James A., Ryan, Kathleen A., Rice, Kenneth, Jaquish, Cashell E., Shuldiner, Alan R., Miller, Michael, Mitchell, Braxton D., Zaghloul, Norann A., Chang, Yen-Pei C., Abe, Namiko, Abecasis, Goncalo, Albert, Christine, Allred, Nicholette P., Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Debora, Arking, Dan, Arnett, Donna K, Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Barnard, John, Barnes, Kathleen, Graham Barr, R., Barron-Casella, Emily, Beaty, Terri, Becker, Diane, Becker, Lewis, Beer, Rebecca, Begum, Ferdouse, Beitelshees, Amber, Benjamin, Emelia, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Boerwinkle, Eric, Borecki, Ingrid, Bowler, Russel, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Bunting, Karen, Burchard, Esteban, Cardwell, Jonathan, Carlson, Sara, Carty, Cara, Casaburi, Richard, Casella, James, Chaffin, Mark, Chang, Christy, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Ida Chen, Yii-Der, Cho, Michael, Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, Das, Sayantan, David, Sean, Davis, Colleen, Daya, Michelle, de Andrade, Mariza, DeBaun, Michael, Deka, Ranjan, DeMeo, Dawn, Devine, Scott, Do, Ron, Duan, Qing, Duggirala, Ravi, Durda, Peter, Dutcher, Susan, Eaton, Charles, Ekunwe, Lynette, Ellinor, Patrick, Emery, Leslie, Farber, Charles, Farnam, Leanna, Fingerlin, Tasha, Flickinger, Matthew, Fornage, Myriam, Franceschini, Nora, Fu, Mao, Fullerton, Malia, Fulton, Lucinda, Gabriel, Stacey, Gan, Weiniu, Gao, Yan, Gass, Margery, Gelb, Bruce, Geng, Xiaoqi (Priscilla), Germer, Soren, Gignoux, Chris, Gladwin, Mark, Glahn, David, Gogarten, Stephanie, Gong, Da-Wei, Goring, Harald, Charles Gu, C., Guan, Yue, Guo, Xiuqing, Haessler, Jeff, Hall, Michael, Harris, Daniel, Hawley, Nicola, He, Jiang, Heavner, Ben, Heckbert, Susan, Hernandez, Ryan, Herrington, David, Hersh, Craig, Hidalgo, Bertha, Hixson, James, Hokanson, John, Hong, Elliott, Hoth, Karin, Hsiung, Chao (Agnes), Huston, Haley, Hwu, Chii Min, Irvin, Marguerite, Jackson, Rebecca, Jain, Deepti, Jaquish, Cashell, Jhun, Min A, Johnsen, Jill, Johnson, Andrew, Johnson, Craig, Johnston, Rich, Jones, Kimberly, Kang, Hyun Min, Kaplan, Robert, Kardia, Sharon, Kathiresan, Sekar, Kaufman, Laura, Kelly, Shannon, Kenny, Eimear, Kessler, Michael, Khan, Alyna, Kinney, Greg, Konkle, Barbara, Kooperberg, Charles, Kramer, Holly, Krauter, Stephanie, Lange, Christoph, Lange, Ethan, Lange, Leslie, Laurie, Cathy, Laurie, Cecelia, LeBoff, Meryl, Lee, Seunggeun, Lee, Wen-Jane, LeFaive, Jonathon, Levine, David, Levy, Dan, Lewis, Joshua, Li, Yun, Lin, Honghuang, Lin, Keng Han, Liu, Simin, Liu, Yongmei, Loos, Ruth, Lunetta, Kathryn, Luo, James, Mahaney, Michael, Make, Barry, Manichaikul, Ani, Manson, JoAnn, Margolin, Lauren, Martin, Lisa, Mathai, Susan, Mathias, Rasika, McArdle, Patrick, McDonald, Merry-Lynn, McFarland, Sean, McGarvey, Stephen, Mei, Hao, Meyers, Deborah, Mikulla, Julie, Min, Nancy, Minear, Mollie, Minster, Ryan L, Mitchell, Braxton, Musani, Solomon, Mwasongwe, Stanford, Mychaleckyj, Josyf C, Nadkarni, Girish, Naik, Rakhi Johns, Natarajan, Pradeep, Nekhai, Sergei, Nickerson, Deborah, North, Kari, O’Connell, Jeff, O’Connor, Tim, Heather, Ochs-Balcom, Pankow, James, Papanicolaou, George, Parker, Margaret, Parsa, Afshin, Pattison, Jessica Tangarone, Penchev, Sara, Peralta, Juan Manuel, Perez, Marco, Perry, James, Peters, Ulrike, Peyser, Patricia, Phillips, Larry, Phillips, Sam, Pollin, Toni, Post, Wendy, Becker, Julia Powers, Boorgula, Meher Preethi, Preuss, Michael, Prokopenko, Dmitry, Psaty, Bruce, Qasba, Pankaj, Qiao, Dandi, Qin, Zhaohui, Rafaels, Nicholas, Raffield, Laura, Ramachandran, Vasan, Rao, D.C., Rasmussen-Torvik, Laura, Ratan, Aakrosh, Redline, Susan, Reed, Robert, Regan, Elizabeth, Reiner, Alex, Rice, Ken, Rich, Stephen, Roden, Dan, Roselli, Carolina, Rotter, Jerome, Ruczinski, Ingo, Russell, Pamela, Ruuska, Sarah, Ryan, Kathleen, Sakornsakolpat, Phuwanat, Salimi, Shabnam, Salzberg, Steven, Sandow, Kevin, Sankaran, Vijay, Scheller, Christopher, Schmidt, Ellen, Schwander, Karen, Schwartz, David, Sciurba, Frank, Seidman, Christine, Sheehan, Vivien, Shetty, Amol, Shetty, Aniket, Hui-Heng Sheu, Wayne, Benjamin Shoemaker, M., Silver, Brian, Silverman, Edwin, Smith, Jennifer, Smith, Josh, Smith, Nicholas, Smith, Tanja, Smoller, Sylvia, Snively, Beverly, Sofer, Tamar, Sotoodehnia, Nona, Stilp, Adrienne, Streeten, Elizabeth, Sung, Yun Ju, Sylvia, Jody, Szpiro, Adam, Sztalryd, Carole, Taliun, Daniel, Tang, Hua, Taub, Margaret, Taylor, Kent, Taylor, Simeon, Telen, Marilyn, Thornton, Timothy A., Tinker, Lesley, Tirschwell, David, Tiwari, Hemant, Tracy, Russell, Tsai, Michael, Vaidya, Dhananjay, VandeHaar, Peter, Vrieze, Scott, Walker, Tarik, Wallace, Robert, Walts, Avram, Wan, Emily, Fei Wang, Fei, Watson, Karol, Weeks, Daniel E., Weir, Bruce, Weiss, Scott, Weng, Lu-Chen, Willer, Cristen, Williams, Kayleen, Keoki Williams, L., Wilson, Carla, Wilson, James, Wong, Quenna, Xu, Huichun, Yanek, Lisa, Yang, Ivana, Yang, Rongze, Zaghloul, Norann, Zhang, Yingze, Zhao, Snow Xueyan, Zhao, Wei, Zheng, Xiuwen, Zhi, Degui, Zhou, Xiang, Zody, Michael, and Zoellner, Sebastian

Published
2018
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49. The Association of Health and Functional Status with Private and Public Religious Practice among Rural, Ethnically Diverse, Older Adults with Diabetes

Author

Arcury, Thomas A., Stafford, Jeanette M., Bell, Ronny A., Golden, Shannon L., Snively, Beverly M., and Quandt, Sara A.

Abstract

Purpose: This analysis describes the association of health and functional status with private and public religious practice among ethnically diverse (African American, Native American, white) rural older adults with diabetes. Methods: Data were collected using a population-based, cross-sectional, stratified, random sample survey of 701 community-dwelling elders with diabetes in two rural North Carolina counties. Outcome measures were private religious practice, church attendance, religious support provided, and religious support received. Correlates included religiosity, health and functional status, and personal characteristics. Statistical significance was assessed using multiple linear regression and logistic regression models. Findings: These rural elders had high levels of religious belief, and private and public religious practice. Religiosity was associated with private and public religious practice. Health and functional status were not associated with private religious practice, but they were associated with public religious practice, such that those with limited functional status participated less in public religious practice. Ethnicity was associated with private religious practice: African Americans had higher levels of private religious practice than Native Americans or whites, while Native Americans had higher levels than whites. Conclusions: Variation in private religious practice among rural older adults is related to personal characteristics and religiosity, while public religious practice is related to physical health, functional status, and religiosity. Declining health may affect the social integration of rural older adults by limiting their ability to participate in a dominant social institution.

Published
2007
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50. Physical Activity among Rural Older Adults with Diabetes

Author

Arcury, Thomas A., Snively, Beverly M., Bell, Ronny A., Smith, Shannon L., Stafford, Jeanette M., Wetmore-Arkader, Lindsay K., and Quandt, Sara A.

Abstract

Purpose: This analysis describes physical activity levels and factors associated with physical activity in an ethnically diverse (African American, Native American, white) sample of rural older adults with diabetes. Method: Data were collected using a population-based, cross-sectional stratified random sample survey of 701 community-dwelling elders with diabetes completed in 2 rural North Carolina counties. Outcome measures were as follows: first, physical activity in the past year, and second, days physically active in the prior week (0-7). Potential correlates included personal and health characteristics and were evaluated for statistical significance using logistic regression models. Findings: About half (52.5%) of the participants stated that they had engaged in physical activity in the past year. Among those, 42.5% stated that they had no days with at least 30 minutes of continuous physical activity in the prior week, while 21.5% reported daily physical activity. Common activities were walking and housework. Correlates of physical activity in the past year and days active in the prior week included measures of physical health and mobility. Conclusions: Physical activity in this ethnically diverse sample of rural elders with diabetes is limited. Effort must be invested to increase physical activity in these groups.

Published
2006
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