Citations 2
The North American Prodromal Synucleinopathy study: protocol for a multi-site, longitudinal, observational study of idiopathic/isolated rapid eye movement sleep behavior disorder
Lim, Miranda, Neilson, Lee E. , Dang, Bianca H. , Locke, Jessica , Cunningham, Hannah, Brewer, Jessica V., Pelletier, Amélie , Miyagawa, Toji , Davis, Albert A. , McLeland, Jennifer S, Criswell, Susan R. , Howell, Michael J., Schenck, Carlos H, Bliwise, Donald L, Miglis, Mitchell G. , Sum-Ping, Oliver, LEE-IANNOTTI, JOYCE, Shprecher, David R, Campbell, M. C., Fields, Julie A. , Gagnon, Jean-François, Kotzbauer, Paul, Gan-Or, Ziv, Ross, Owen A, Kantarci, Kejal, Lowe, VJ, Hu, Xiaoping , Martens, Kaylena A Ehgoetz, Hu, M, Xiong, Chengjie, Postuma, Ronald B, Boeve, Bradley F, Ju, Yo‐El S. , Zangrilli, Maggie, Kraft, Ruth, Tucker, Kelsey, Landsell, Amanda, Butler, Gareth, Blake, Tyler, Wang, Amy J. , Lavadia, Loren, Orford, Jessica, Otterbein, Abigail, Gamache, David E., Rivera, Adreanne, Siegler, Jordan, Nguyen, Vince, Machnik, Jannika , Viviani, Adele M.L., Powers, Katherine, Keil, Alison, Ligman, Brittany R. , Olivo, Cosette, Bryant-Ekstrand, Mohini, Hansen, A. G., Ekis, Arlynn E., Nagum, Ryn, Bates, Leland, Schroeder, Carly, Bryants, Marina, Bauman, Jessica, Arik, Anam J., Gan‐Or, Ziv , Howell, Michael J. , Sum‐Ping, Oliver , Lim, Miranda M , Elliott, Jonathan E , Cunningham, Hannah , St Louis, E K , Criswell, Susan R , Schenck, Carlos H , Avidan, Alon Y , Trotti, Lynn Marie , Bliwise, Donald L , Huddleston, Daniel E , Miglis, Mitchell G , Duff, Kevin , Singer, Wolfgang , Gan-Or, Ziv , Ross, Owen A , Kantarci, Kejal , Hu, Michele T M , Boeve, Brad , Howell, Michael J , Neilson, Lee E , Sum-Ping, Oliver , Elliott, Jonathan E. , Locke, Jessica R, Dennis, Laura E. , Dovek, Laura , Louis, Erik K. St. , McCarter, Stuart J. , McLeland, Jennifer , Howell, Michael J, Schenck, Carlos H. , Avidan, Alon Y. , Trotti, Lynn Marie , Bliwise, Donald L. , Huddleston, Daniel E. , Videnovic, Aleksandar , Lee‐Iannotti, Joyce , Shprecher, David , Duff, Kevin , Ferman, Tanis J. , Campbell, Meghan C., Kotzbauer, Paul T. , Ross, Owen A. , Kantarci, Kejal , Martens, Kaylena Ehgoetz, Xiong, Chengjie , Postuma, Ronald B. , Boeve, Bradley F. , Heath, Brianna E. , Powers, Katherine , Bryant‐Ekstrand, Mohini , Hansen, Abigail
SLEEP Advances | January 17, 2026 | Volume: 7 | Issue: 1 | Pages: No page available
Abstract Isolated/idiopathic rapid eye movement sleep behavior disorder (iRBD) is a usually prodromal manifestation of neurodegenerative disorders with α-synuclein pathology: Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Clinical trials in the iRBD population face substantial barriers: limited access to well-characterized cohorts, inconsistent assessment protocols across centers, and the absence of validated biomarkers of disease burden. The North American Prodromal Synucleinopathy (NAPS) Consortium was established to address these challenges and facilitate clinical trials for neuroprotective therapies targeting synucleinopathy at the earliest known stages. In this multi-site, longitudinal, observational study, nine academic centers across North America will enroll and follow over 500 individuals with iRBD from existing sleep centers. Sixty control participants, matched for age, sex, and race will also be recruited. A harmonized protocol—including a standardized clinical battery assessing motor, cognitive, autonomic, psychiatric, sensory, and sleep function; structured diagnostic adjudication; biospecimen collection; and centralized analysis of both polysomnography and neuroimaging data—is outlined herein and reflects NAPS Stage 2. Each participants completes these assessments annually, and are replaced in the event of phenoconversion. By unifying assessments and expanding geographic reach, NAPS lays the groundwork for efficient, well-powered clinical trials designed to delay or prevent progression of iRBD to overt PD, DLB, or MSA—ultimately enabling earlier, more effective therapeutic intervention for neurodegenerative disease. Registered at clinicaltrials.gov (NCT05826457).
Genetic Architecture of Abdominal Aortic Aneurysm in the Million Veteran Program
Klarin, Derek , Judy, Renae , Dikilitas, Ozan , Wolford, Brooke N. , Paranjpe, Ishan , Levin, Michael G. , Pan, Cuiping , Tcheandjieu, Catherine , Spin, Joshua M. , Assimes, Themistocles L. , Nyrønning, Linn Åldstedt , Mattsson, Erney , Denny, Joshua C. , Zhang, Yanfei , Jarvik, Gail P. , Gharavi, Ali G. , Harley, John B. , Mentch, Frank , Håkonarson, Håkon , Skogholt, Anne Heidi , Thomas, Laurent F. , Gabrielsen, Maiken E. , Zhou, Wei , Fritsche, Lars G. , Huang, Jie , Natarajan, Pradeep , Sun, Yan V. , DuVall, Scott L. , Cho, Kelly , Chang, Kyong‐Mi , Wilson, Peter W.F. , O’Donnell, Christopher J., Kathiresan, Sekar , Scali, Salvatore T. , Jones, Gregory T. , Bown, Matthew J. , Nadkarni, Girish N. , Ritchie, Marylyn D. , Tsao, Philip S. , Gaziano, J. Michael , Ramoni, Rachel , Breeling, Jim, Huang, Grant D. , Muralidhar, Sumitra , O’Donnell, Christopher J. , Romero, Jonathan , Tsao, Philip S., Moser, Jennifer , Whitbourne, Stacey B. , Brewer, Jessica V., Warren, Stuart, Argyres, Dean P., Tsao, Philip S., Stephens, Brady, Brophy, Mary T. , Humphries, Donald E., Shayan, Shahpoor, O’Donnell, Christopher J., Pyarajan, Saiju , Tsao, Philip S., Dell’Italia, Louis J. , Zablocki, Clement J., Beckham, Jean, Wells, John A. , Gutierrez, Salvador, Kaminsky, Laurence S., Villareal, Gerardo, Xu, Junzhe, Hamner, Mark B. , Haddock, Kathlyn Sue, Bhushan, Sujata, Iruvanti, Pran, Godschalk, Michael, Buford, Malcolm, Mastorides, Stephen , Ratcliffe, Nora, Flórez, Hermes , Swann, Alan C. , Murdoch, Maureen, Yeh, Shing Shing, Washburn, Ronald G., Jhala, Darshana , Aguayo, Samuel M., Cohen, David , Sharma, Satish, Callaghan, John, Oursler, Kris Ann, Ahuja, Sunil K. , Gutierrez, Amparo, Schifman, Ronald, Greco, Jennifer , Oehlert, Mary E. , Wallbom, Agnes, Fernando, Ronald, Morgan, Timothy R. , Stapley, Todd, Anderson, Gwenevere, Sonel, Elif, Fayad, Joseph, Hung, Adriana M. , Lichy, Jack, Hurley, Robin A. , Hakonarson, Hakon , Denny, Joshua C , Jarvik, Gail P , Dikilitas, Ozan , Assimes, Themistocles L , Natarajan, Pradeep , Wolford, Brooke N , Scali, Salvatore , Chang, Kyong-Mi , Tsao, Philip S , Verma, Shefali S. , Lynch, Julie A. , Edwards, Todd L. , Larson, Eric B. , Lee, Ming Ta Michael , Carrell, David , Pacheco, Jennifer A. , Hveem, Kristian , Nielsen, Jonas Bille , Rader, Daniel J , O’Donnell, Christopher J., Berceli, Scott A. , Willer, Cristen J , Kullo, Iftikhar J. , Damrauer, Scott M , Beckham, Jean C , Tsao, Philip S., Concato, John , Tsao, Philip S., Do, Nhan , Nguyen, Xuan‐Mai T. , O’Donnell, Christopher J., Tsao, Philip S., Hauser, Elizabeth R. , Zhao, Hongyu , McArdle, Rachel , Whittle, Jeff , Beckham, Jean, Wells, John, Gibson, Gretchen , Kinlay, Scott , Ballas, Zuhair K. , Klein, Jon , Sriram, Peruvemba , Washburn, Ronald, Whooley, Mary A. , Rauchman, Michael I. , Servatius, Richard J. , Sherman, Scott E. , Boyko, Edward J. , Meyer, Laurence , Gupta, Samir , Robey, R. Brooks , Striker, Rob
Circulation | September 28, 2020 | Volume: 142 | Issue: 17 | Pages: 1633-1646
10.1161/circulationaha.120.047544
Background: Abdominal aortic aneurysm (AAA) is an important cause of cardiovascular mortality; however, its genetic determinants remain incompletely defined. In total, 10 previously identified risk loci explain a small fraction of AAA heritability. Methods: We performed a genome-wide association study in the Million Veteran Program testing ≈18 million DNA sequence variants with AAA (7642 cases and 172 172 controls) in veterans of European ancestry with independent replication in up to 4972 cases and 99 858 controls. We then used mendelian randomization to examine the causal effects of blood pressure on AAA. We examined the association of AAA risk variants with aneurysms in the lower extremity, cerebral, and iliac arterial beds, and derived a genome-wide polygenic risk score (PRS) to identify a subset of the population at greater risk for disease. Results: Through a genome-wide association study, we identified 14 novel loci, bringing the total number of known significant AAA loci to 24. In our mendelian randomization analysis, we demonstrate that a genetic increase of 10 mm Hg in diastolic blood pressure (odds ratio, 1.43 [95% CI, 1.24–1.66]; P =1.6×10 −6 ), as opposed to systolic blood pressure (odds ratio, 1.06 [95% CI, 0.97–1.15]; P =0.2), likely has a causal relationship with AAA development. We observed that 19 of 24 AAA risk variants associate with aneurysms in at least 1 other vascular territory. A 29-variant PRS was strongly associated with AAA (odds ratio PRS , 1.26 [95% CI, 1.18–1.36]; P PRS =2.7×10 −11 per SD increase in PRS), independent of family history and smoking risk factors (odds ratio PRS+family history+smoking , 1.24 [95% CI, 1.14–1.35]; P PRS =1.27×10 −6 ). Using this PRS, we identified a subset of the population with AAA prevalence greater than that observed in screening trials informing current guidelines. Conclusions: We identify novel AAA genetic associations with therapeutic implications and identify a subset of the population at significantly increased genetic risk of AAA independent of family history. Our data suggest that extending current screening guidelines to include testing to identify those with high polygenic AAA risk, once the cost of genotyping becomes comparable with that of screening ultrasound, would significantly increase the yield of current screening at reasonable cost.