Person:
Cade, Brian

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Cade

First Name

Brian

Name

Cade, Brian
Author's Publications: search.filters.isAuthorOfPublication.9db98028-e557-4d60-8e85-84b796e432fa

Search Results

Now showing 1 - 5 of 5
  • Thumbnail Image
    Publication
    Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African Ancestry Anthropometry Genetics Consortium
    (Public Library of Science, 2017) Ng, Maggie C. Y.; Graff, Mariaelisa; Lu, Yingchang; Justice, Anne E.; Mudgal, Poorva; Liu, Ching-Ti; Young, Kristin; Yanek, Lisa R.; Feitosa, Mary F.; Wojczynski, Mary K.; Rand, Kristin; Brody, Jennifer A.; Cade, Brian; Dimitrov, Latchezar; Duan, Qing; Guo, Xiuqing; Lange, Leslie A.; Nalls, Michael A.; Okut, Hayrettin; Tajuddin, Salman M.; Tayo, Bamidele O.; Vedantam, Sailaja; Bradfield, Jonathan P.; Chen, Guanjie; Chen, Wei-Min; Chesi, Alessandra; Irvin, Marguerite R.; Padhukasahasram, Badri; Smith, Jennifer A.; Zheng, Wei; Allison, Matthew A.; Ambrosone, Christine B.; Bandera, Elisa V.; Bartz, Traci M.; Berndt, Sonja I.; Bernstein, Leslie; Blot, William J.; Bottinger, Erwin P.; Carpten, John; Chanock, Stephen J.; Chen, Yii-Der Ida; Conti, David V.; Cooper, Richard S.; Fornage, Myriam; Freedman, Barry I.; Garcia, Melissa; Goodman, Phyllis J.; Hsu, Yu-Han; Hu, Jennifer; Huff, Chad D.; Ingles, Sue A.; John, Esther M.; Kittles, Rick; Klein, Eric; Li, Jin; McKnight, Barbara; Nayak, Uma; Nemesure, Barbara; Ogunniyi, Adesola; Olshan, Andrew; Press, Michael F.; Rohde, Rebecca; Rybicki, Benjamin A.; Salako, Babatunde; Sanderson, Maureen; Shao, Yaming; Siscovick, David S.; Stanford, Janet L.; Stevens, Victoria L.; Stram, Alex; Strom, Sara S.; Vaidya, Dhananjay; Witte, John S.; Yao, Jie; Zhu, Xiaofeng; Ziegler, Regina G.; Zonderman, Alan B.; Adeyemo, Adebowale; Ambs, Stefan; Cushman, Mary; Faul, Jessica D.; Hakonarson, Hakon; Levin, Albert M.; Nathanson, Katherine L.; Ware, Erin B.; Weir, David R.; Zhao, Wei; Zhi, Degui; Arnett, Donna K.; Grant, Struan F. A.; Kardia, Sharon L. R.; Oloapde, Olufunmilayo I.; Rao, D. C.; Rotimi, Charles N.; Sale, Michele M.; Williams, L. Keoki; Zemel, Babette S.; Becker, Diane M.; Borecki, Ingrid B.; Evans, Michele K.; Harris, Tamara B.; Hirschhorn, Joel; Li, Yun; Patel, Sanjay R.; Psaty, Bruce M.; Rotter, Jerome I.; Wilson, James G.; Bowden, Donald W.; Cupples, L. Adrienne; Haiman, Christopher A.; Loos, Ruth J. F.; North, Kari E.
    Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus (TCF7L2/HABP2) for WHRadjBMI and eight previously established loci at P < 5×10−8: seven for BMI, and one for WHRadjBMI in African ancestry individuals. An additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMI when combined with European GWAS. In the sex-stratified analyses, we identified three novel loci for BMI (INTS10/LPL and MLC1 in men, IRX4/IRX2 in women) and four for WHRadjBMI (SSX2IP, CASC8, PDE3B and ZDHHC1/HSD11B2 in women) in individuals of African ancestry or both African and European ancestry. For four of the novel variants, the minor allele frequency was low (<5%). In the trans-ethnic fine mapping of 47 BMI loci and 27 WHRadjBMI loci that were locus-wide significant (P < 0.05 adjusted for effective number of variants per locus) from the African ancestry sex-combined and sex-stratified analyses, 26 BMI loci and 17 WHRadjBMI loci contained ≤ 20 variants in the credible sets that jointly account for 99% posterior probability of driving the associations. The lead variants in 13 of these loci had a high probability of being causal. As compared to our previous HapMap imputed GWAS for BMI and WHRadjBMI including up to 71,412 and 27,350 African ancestry individuals, respectively, our results suggest that 1000 Genomes imputation showed modest improvement in identifying GWAS loci including low frequency variants. Trans-ethnic meta-analyses further improved fine mapping of putative causal variants in loci shared between the African and European ancestry populations.
  • Thumbnail Image
    Publication
    Rare variants in fox-1 homolog A (RBFOX1) are associated with lower blood pressure
    (Public Library of Science, 2017) He, Karen Y.; Wang, Heming; Cade, Brian; Nandakumar, Priyanka; Giri, Ayush; Ware, Erin B.; Haessler, Jeffrey; Liang, Jingjing; Smith, Jennifer A.; Franceschini, Nora; Le, Thu H.; Kooperberg, Charles; Edwards, Todd L.; Kardia, Sharon L. R.; Lin, Xihong; Chakravarti, Aravinda; Redline, Susan; Zhu, Xiaofeng
    Many large genome-wide association studies (GWAS) have identified common blood pressure (BP) variants. However, most of the identified BP variants do not overlap with the linkage evidence observed from family studies. We thus hypothesize that multiple rare variants contribute to the observed linkage evidence. We performed linkage analysis using 517 individuals in 130 European families from the Cleveland Family Study (CFS) who have been genotyped on the Illumina OmniExpress Exome array. The largest linkage peak was observed on chromosome 16p13 (MLOD = 2.81) for systolic blood pressure (SBP). Follow-up conditional linkage and association analyses in the linkage region identified multiple rare, coding variants in RBFOX1 associated with reduced SBP. In a 17-member CFS family, carriers of the missense variant rs149974858 are normotensive despite being obese (average BMI = 60 kg/m2). Gene-based association test of rare variants using SKAT-O showed significant association with SBP (p-value = 0.00403) and DBP (p-value = 0.0258) in the CFS participants and the association was replicated in large independent replication studies (N = 57,234, p-value = 0.013 for SBP, 0.0023 for PP). RBFOX1 is expressed in brain tissues, the atrial appendage and left ventricle in the heart, and in skeletal muscle tissues, organs/tissues which are potentially related to blood pressure. Our study showed that associations of rare variants could be efficiently detected using family information.
  • Thumbnail Image
    Publication
    Beyond type 2 diabetes, obesity and hypertension: an axis including sleep apnea, left ventricular hypertrophy, endothelial dysfunction, and aortic stiffness among Mexican Americans in Starr County, Texas
    (BioMed Central, 2016) Hanis, Craig L.; Redline, Susan; Cade, Brian; Bell, Graeme I.; Cox, Nancy J.; Below, Jennifer E.; Brown, Eric L.; Aguilar, David
    Background: There is an increasing appreciation for a series of less traditional risk factors that should not be ignored when considering type 2 diabetes, obesity, hypertension, and cardiovascular disease. These include aortic stiffness, cardiac structure, impaired endothelial function and obstructive sleep apnea. They are associated to varying degrees with each disease categorization and with each other. It is not clear whether they represent additional complications, concomitants or antecedents of disease. Starr County, Texas, with its predominantly Mexican American population has been shown previously to bear a disproportionate burden of the major disease categories, but little is known about the distribution of these less traditional factors. Methods: Type 2 diabetes, obesity and hypertension frequencies were determined through a systematic survey of Starr County conducted from 2002 to 2006. Individuals from this examination and an enriched set with type 2 diabetes were re-examined from 2010 to 2014 including assessment of cardiac structure, sleep apnea, endothelial function and aortic stiffness. Individual and combined frequencies of these inter-related (i.e., axis) conditions were estimated and associations evaluated. Results: Household screening of 5230 individuals aged 20 years and above followed by direct physical assessment of 1610 identified 23.7 % of men and 26.7 % of women with type 2 diabetes, 46.2 and 49.5 % of men and women, respectively with obesity and 32.1 and 32.4 % with hypertension. Evaluation of pulse wave velocity, left ventricular mass, endothelial function and sleep apnea identified 22.3, 12.7, 48.6 and 45.2 % of men as having “at risk” values for each condition, respectively. Corresponding numbers in women were 16.0, 17.9, 23.6 and 28.8 %. Cumulatively, 88 % of the population has one or more of these while 50 % have three or more. Conclusions: The full axis of conditions is high among Mexican Americans in Starr County, Texas. Individual and joint patterns suggest a genesis well before overt disease. Whether they are all mediated by common underlying factors or whether there exist multiple mechanisms remains to be seen. Electronic supplementary material The online version of this article (doi:10.1186/s12933-016-0405-6) contains supplementary material, which is available to authorized users.
  • Thumbnail Image
    Publication
    Association of Genetic Loci with Sleep Apnea in European Americans and African-Americans: The Candidate Gene Association Resource (CARe)
    (Public Library of Science, 2012) Patel, Sanjay R.; Goodloe, Robert; De, Gourab; Kowgier, Matthew; Weng, Jia; Buxbaum, Sarah G.; Cade, Brian; Fulop, Tibor; Gharib, Sina A.; Gottlieb, Daniel; Hillman, David; Larkin, Emma K.; Lauderdale, Diane S.; Li, Li; Mukherjee, Sutapa; Palmer, Lyle; Zee, Phyllis; Zhu, Xiaofeng; Redline, Susan
    Although obstructive sleep apnea (OSA) is known to have a strong familial basis, no genetic polymorphisms influencing apnea risk have been identified in cross-cohort analyses. We utilized the National Heart, Lung, and Blood Institute (NHLBI) Candidate Gene Association Resource (CARe) to identify sleep apnea susceptibility loci. Using a panel of 46,449 polymorphisms from roughly 2,100 candidate genes on a customized Illumina iSelect chip, we tested for association with the apnea hypopnea index (AHI) as well as moderate to severe OSA (AHI≥15) in 3,551 participants of the Cleveland Family Study and two cohorts participating in the Sleep Heart Health Study. Among 647 African-Americans, rs11126184 in the pleckstrin (PLEK) gene was associated with OSA while rs7030789 in the lysophosphatidic acid receptor 1 (LPAR1) gene was associated with AHI using a chip-wide significance threshold of p-value<2×\(10^{−6}\). Among 2,904 individuals of European ancestry, rs1409986 in the prostaglandin E2 receptor (PTGER3) gene was significantly associated with OSA. Consistency of effects between rs7030789 and rs1409986 in LPAR1 and PTGER3 and apnea phenotypes were observed in independent clinic-based cohorts. Novel genetic loci for apnea phenotypes were identified through the use of customized gene chips and meta-analyses of cohort data with replication in clinic-based samples. The identified SNPs all lie in genes associated with inflammation suggesting inflammation may play a role in OSA pathogenesis.
  • No Thumbnail Available
    Publication
    Inherited Causes of Clonal Haematopoiesis in 97,691 Whole Genomes
    (Springer Science and Business Media LLC, 2020-10-14) Bick, Alexander; Weinstock, Joshua S.; Nandakumar, Satish K.; Fulco, Charles P.; Bao, Erik; Zekavat, Seyedeh M.; Szeto, Mindy D.; Liao, Xiaotian; Leventhal, Matthew J.; Nasser, Joseph; Chang, Kyle; Laurie, Cecelia; Burugula, Bala Bharathi; Gibson, Christopher J.; Niroula, Abhishek; Lin, Amy; Taub, Margaret A.; Aguet, Francois; Ardlie, Kristin; Mitchell, Braxton D.; Barnes, Kathleen C.; Moscati, Arden; Fornage, Myriam; Redline, Susan; Psaty, Bruce M.; Silverman, Edwin; Weiss, Scott; Palmer, Nicholette D.; Vasan, Ramachandran S.; Burchard, Esteban G.; Kardia, Sharon L. R.; He, Jiang; Kaplan, Robert C.; Smith, Nicholas L.; Arnett, Donna K.; Schwartz, David A.; Correa, Adolfo; de Andrade, Mariza; Guo, Xiuqing; Konkle, Barbara A.; Custer, Brian; Peralta, Juan M.; Gui, Hongsheng; Meyers, Deborah A.; McGarvey, Stephen T.; Chen, Ida Yii-Der; Shoemaker, M. Benjamin; Peyser, Patricia A.; Broome, Jai G.; Gogarten, Stephanie M.; Wang, Fei Fei; Wong, Quenna; Montasser, May E.; Daya, Michelle; Kenny, Eimear E.; North, Kari E.; Launer, Lenore J.; Cade, Brian; Bis, Joshua C.; Cho, Michael; Lasky-Su, Jessica; Bowden, Donald W.; Cupples, L. Adrienne; Mak, Angel C. Y.; Becker, Lewis C.; Smith, Jennifer A.; Kelly, Tanika N.; Aslibekyan, Stella; Heckbert, Susan R.; Tiwari, Hemant K.; Yang, Ivana V.; Heit, John A.; Lubitz, Steven; Johnsen, Jill M.; Curran, Joanne E.; Wenzel, Sally E.; Weeks, Daniel E.; Rao, Dabeeru C.; Darbar, Dawood; Moon, Jee-Young; Tracy, Russell P.; Buth, Erin J.; Rafaels, Nicholas; Loos, Ruth J. F.; Durda, Peter; Liu, Yongmei; Hou, Lifang; Lee, Jiwon; Kachroo, Priyadarshini; Freedman, Barry I.; Levy, Daniel; Bielak, Lawrence F.; Hixson, James E.; Floyd, James S.; Whitsel, Eric A.; Ellinor, Patrick; Irvin, Marguerite R.; Fingerlin, Tasha E.; Raffield, Laura M.; Armasu, Sebastian M.; Wheeler, Marsha M.; Sabino, Ester C.; Blangero, John; Williams, L. Keoki; Levy, Bruce; Sheu, Wayne Huey-Herng; Roden, Dan M.; Boerwinkle, Eric; Manson, JoAnn; Mathias, Rasika A.; Desai, Pinkal; Taylor, Kent D.; Johnson, Andrew D.; Auer, Paul L.; Kooperberg, Charles; Laurie, Cathy C.; Blackwell, Thomas W.; Smith, Albert V.; Zhao, Hongyu; Lange, Ethan; Lange, Leslie; Rich, Stephen S.; Rotter, Jerome I.; Wilson, James G.; Scheet, Paul; Kitzman, Jacob O.; Lander, Eric; Engreitz, Jesse; Ebert, Benjamin; Reiner, Alexander P.; Jaiswal, Siddhartha; Abecasis, Gonçalo; Sankaran, Vijay; Kathiresan, Sekar; Natarajan, Pradeep
    Age is the dominant risk factor for most chronic human diseases; yet the mechanisms by which aging confers this risk are largely unknown. Recently, the age-related acquisition of somatic mutations in regenerating hematopoietic stem cell populations leading to clonal expansion was associated with both hematologic cancer and coronary heart disease5, a phenomenon termed ‘Clonal Hematopoiesis of Indeterminate Potential’ (CHIP). Simultaneous germline and somatic whole genome sequence analysis now provides the opportunity to identify root causes of CHIP. Here, we analyze high-coverage whole genome sequences from 97,691 participants of diverse ancestries in the NHLBI TOPMed program and identify 4,229 individuals with CHIP. We identify associations with blood cell, lipid, and inflammatory traits specific to different CHIP genes. Association of a genome-wide set of germline genetic variants identified three genetic loci associated with CHIP status, including one locus at TET2 that was African ancestry specific. In silico-informed in vitro evaluation of the TET2 germline locus identified a causal variant that disrupts a TET2 distal enhancer resulting in increased hematopoietic stem cell self-renewal. Overall, we observe that germline genetic variation shapes hematopoietic stem cell function leading to CHIP through mechanisms that are both specific to clonal hematopoiesis and shared mechanisms leading to somatic mutations across tissues.