TY - JOUR A1 - Van Hout, Cristopher V. A1 - Tachmazidou, Ioanna A1 - Backman, Joshua D. A1 - Hoffman, Joshua D. A1 - Liu, Daren A1 - Pandey, Ashutosh K. A1 - Gonzaga-Jauregui, Claudia A1 - Khalid, Shareef A1 - Ye, Bin A1 - Banerjee, Nilanjana A1 - Li, Alexander H. A1 - O'Dushlaine, Colm A1 - Marcketta, Anthony A1 - Staples, Jeffrey A1 - Schurmann, Claudia A1 - Hawes, Alicia A1 - Maxwell, Evan A1 - Barnard, Leland A1 - Lopez, Alexander A1 - Penn, John A1 - Habegger, Lukas A1 - Blumenfeld, Andrew L. A1 - Bai, Xiaodong A1 - O'Keeffe, Sean A1 - Yadav, Ashish A1 - Praveen, Kavita A1 - Jones, Marcus A1 - Salerno, William J. A1 - Chung, Wendy K. A1 - Surakka, Ida A1 - Willer, Cristen J. A1 - Hveem, Kristian A1 - Leader, Joseph B. A1 - Carey, David J. A1 - Ledbetter, David H. A1 - Cardon, Lon A1 - Yancopoulos, George D. A1 - Economides, Aris A1 - Coppola, Giovanni A1 - Shuldiner, Alan R. A1 - Balasubramanian, Suganthi A1 - Cantor, Michael A1 - Nelson, Matthew R. A1 - Whittaker, John A1 - Reid, Jeffrey G. A1 - Marchini, Jonathan A1 - Overton, John D. A1 - Scott, Robert A. A1 - Abecasis, Goncalo R. A1 - Yerges-Armstrong, Laura M. A1 - Baras, Aris T1 - Exome sequencing and characterization of 49,960 individuals in the UK Biobank JF - Nature : the international weekly journal of science N2 - The UK Biobank is a prospective study of 502,543 individuals, combining extensive phenotypic and genotypic data with streamlined access for researchers around the world(1). Here we describe the release of exome-sequence data for the first 49,960 study participants, revealing approximately 4 million coding variants (of which around 98.6% have a frequency of less than 1%). The data include 198,269 autosomal predicted loss-of-function (LOF) variants, a more than 14-fold increase compared to the imputed sequence. Nearly all genes (more than 97%) had at least one carrier with a LOF variant, and most genes (more than 69%) had at least ten carriers with a LOF variant. We illustrate the power of characterizing LOF variants in this population through association analyses across 1,730 phenotypes. In addition to replicating established associations, we found novel LOF variants with large effects on disease traits, includingPIEZO1on varicose veins,COL6A1on corneal resistance,MEPEon bone density, andIQGAP2andGMPRon blood cell traits. We further demonstrate the value of exome sequencing by surveying the prevalence of pathogenic variants of clinical importance, and show that 2% of this population has a medically actionable variant. Furthermore, we characterize the penetrance of cancer in carriers of pathogenicBRCA1andBRCA2variants. Exome sequences from the first 49,960 participants highlight the promise of genome sequencing in large population-based studies and are now accessible to the scientific community.
Exome sequences from the first 49,960 participants in the UK Biobank highlight the promise of genome sequencing in large population-based studies and are now accessible to the scientific community. KW - clinical exome KW - breast-cancer KW - mutations KW - recommendations KW - gene KW - metaanalysis KW - variants, KW - BRCA1 KW - risk KW - susceptibility Y1 - 2020 U6 - https://doi.org/10.1038/s41586-020-2853-0 SN - 0028-0836 SN - 1476-4687 VL - 586 IS - 7831 SP - 749 EP - 756 PB - Macmillan Publishers Limited CY - London ER - TY - JOUR A1 - Koenig, Julian A1 - Abler, Birgit A1 - Agartz, Ingrid A1 - akerstedt, Torbjorn A1 - Andreassen, Ole A. A1 - Anthony, Mia A1 - Baer, Karl-Juergen A1 - Bertsch, Katja A1 - Brown, Rebecca C. A1 - Brunner, Romuald A1 - Carnevali, Luca A1 - Critchley, Hugo D. A1 - Cullen, Kathryn R. A1 - de Geus, Eco J. C. A1 - de la Cruz, Feliberto A1 - Dziobek, Isabel A1 - Ferger, Marc D. A1 - Fischer, Hakan A1 - Flor, Herta A1 - Gaebler, Michael A1 - Gianaros, Peter J. A1 - Giummarra, Melita J. A1 - Greening, Steven G. A1 - Guendelman, Simon A1 - Heathers, James A. J. A1 - Herpertz, Sabine C. A1 - Hu, Mandy X. A1 - Jentschke, Sebastian A1 - Kaess, Michael A1 - Kaufmann, Tobias A1 - Klimes-Dougan, Bonnie A1 - Koelsch, Stefan A1 - Krauch, Marlene A1 - Kumral, Deniz A1 - Lamers, Femke A1 - Lee, Tae-Ho A1 - Lekander, Mats A1 - Lin, Feng A1 - Lotze, Martin A1 - Makovac, Elena A1 - Mancini, Matteo A1 - Mancke, Falk A1 - Mansson, Kristoffer N. T. A1 - Manuck, Stephen B. A1 - Mather, Mara A1 - Meeten, Frances A1 - Min, Jungwon A1 - Mueller, Bryon A1 - Muench, Vera A1 - Nees, Frauke A1 - Nga, Lin A1 - Nilsonne, Gustav A1 - Ordonez Acuna, Daniela A1 - Osnes, Berge A1 - Ottaviani, Cristina A1 - Penninx, Brenda W. J. H. A1 - Ponzio, Allison A1 - Poudel, Govinda R. A1 - Reinelt, Janis A1 - Ren, Ping A1 - Sakaki, Michiko A1 - Schumann, Andy A1 - Sorensen, Lin A1 - Specht, Karsten A1 - Straub, Joana A1 - Tamm, Sandra A1 - Thai, Michelle A1 - Thayer, Julian F. A1 - Ubani, Benjamin A1 - van Der Mee, Denise J. A1 - van Velzen, Laura S. A1 - Ventura-Bort, Carlos A1 - Villringer, Arno A1 - Watson, David R. A1 - Wei, Luqing A1 - Wendt, Julia A1 - Schreiner, Melinda Westlund A1 - Westlye, Lars T. A1 - Weymar, Mathias A1 - Winkelmann, Tobias A1 - Wu, Guo-Rong A1 - Yoo, Hyun Joo A1 - Quintana, Daniel S. T1 - Cortical thickness and resting-state cardiac function across the lifespan BT - a cross-sectional pooled mega-analysis JF - Psychophysiology : journal of the Society for Psychophysiological Research N2 - Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12-87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS-or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research. KW - aging KW - autonomic nervous system KW - cortical thickness KW - heart rate KW - heart KW - rate variability KW - sex Y1 - 2020 U6 - https://doi.org/10.1111/psyp.13688 SN - 0048-5772 SN - 1469-8986 VL - 58 IS - 7 PB - Wiley CY - Hoboken ER -