@article{VanHoutTachmazidouBackmanetal.2020, author = {Van Hout, Cristopher V. and Tachmazidou, Ioanna and Backman, Joshua D. and Hoffman, Joshua D. and Liu, Daren and Pandey, Ashutosh K. and Gonzaga-Jauregui, Claudia and Khalid, Shareef and Ye, Bin and Banerjee, Nilanjana and Li, Alexander H. and O'Dushlaine, Colm and Marcketta, Anthony and Staples, Jeffrey and Schurmann, Claudia and Hawes, Alicia and Maxwell, Evan and Barnard, Leland and Lopez, Alexander and Penn, John and Habegger, Lukas and Blumenfeld, Andrew L. and Bai, Xiaodong and O'Keeffe, Sean and Yadav, Ashish and Praveen, Kavita and Jones, Marcus and Salerno, William J. and Chung, Wendy K. and Surakka, Ida and Willer, Cristen J. and Hveem, Kristian and Leader, Joseph B. and Carey, David J. and Ledbetter, David H. and Cardon, Lon and Yancopoulos, George D. and Economides, Aris and Coppola, Giovanni and Shuldiner, Alan R. and Balasubramanian, Suganthi and Cantor, Michael and Nelson, Matthew R. and Whittaker, John and Reid, Jeffrey G. and Marchini, Jonathan and Overton, John D. and Scott, Robert A. and Abecasis, Goncalo R. and Yerges-Armstrong, Laura M. and Baras, Aris}, title = {Exome sequencing and characterization of 49,960 individuals in the UK Biobank}, series = {Nature : the international weekly journal of science}, volume = {586}, journal = {Nature : the international weekly journal of science}, number = {7831}, publisher = {Macmillan Publishers Limited}, address = {London}, organization = {Regeneron Genetics Ctr}, issn = {0028-0836}, doi = {10.1038/s41586-020-2853-0}, pages = {749 -- 756}, year = {2020}, abstract = {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.}, language = {en} } @article{KoenigAblerAgartzetal.2020, author = {Koenig, Julian and Abler, Birgit and Agartz, Ingrid and akerstedt, Torbjorn and Andreassen, Ole A. and Anthony, Mia and Baer, Karl-Juergen and Bertsch, Katja and Brown, Rebecca C. and Brunner, Romuald and Carnevali, Luca and Critchley, Hugo D. and Cullen, Kathryn R. and de Geus, Eco J. C. and de la Cruz, Feliberto and Dziobek, Isabel and Ferger, Marc D. and Fischer, Hakan and Flor, Herta and Gaebler, Michael and Gianaros, Peter J. and Giummarra, Melita J. and Greening, Steven G. and Guendelman, Simon and Heathers, James A. J. and Herpertz, Sabine C. and Hu, Mandy X. and Jentschke, Sebastian and Kaess, Michael and Kaufmann, Tobias and Klimes-Dougan, Bonnie and Koelsch, Stefan and Krauch, Marlene and Kumral, Deniz and Lamers, Femke and Lee, Tae-Ho and Lekander, Mats and Lin, Feng and Lotze, Martin and Makovac, Elena and Mancini, Matteo and Mancke, Falk and Mansson, Kristoffer N. T. and Manuck, Stephen B. and Mather, Mara and Meeten, Frances and Min, Jungwon and Mueller, Bryon and Muench, Vera and Nees, Frauke and Nga, Lin and Nilsonne, Gustav and Ordonez Acuna, Daniela and Osnes, Berge and Ottaviani, Cristina and Penninx, Brenda W. J. H. and Ponzio, Allison and Poudel, Govinda R. and Reinelt, Janis and Ren, Ping and Sakaki, Michiko and Schumann, Andy and Sorensen, Lin and Specht, Karsten and Straub, Joana and Tamm, Sandra and Thai, Michelle and Thayer, Julian F. and Ubani, Benjamin and van Der Mee, Denise J. and van Velzen, Laura S. and Ventura-Bort, Carlos and Villringer, Arno and Watson, David R. and Wei, Luqing and Wendt, Julia and Schreiner, Melinda Westlund and Westlye, Lars T. and Weymar, Mathias and Winkelmann, Tobias and Wu, Guo-Rong and Yoo, Hyun Joo and Quintana, Daniel S.}, title = {Cortical thickness and resting-state cardiac function across the lifespan}, series = {Psychophysiology : journal of the Society for Psychophysiological Research}, volume = {58}, journal = {Psychophysiology : journal of the Society for Psychophysiological Research}, number = {7}, publisher = {Wiley}, address = {Hoboken}, issn = {0048-5772}, doi = {10.1111/psyp.13688}, pages = {16}, year = {2020}, abstract = {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.}, language = {en} }