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 - Urbach, Tina A1 - Fay, Doris T1 - Leader member exchange in leaders’ support for voice BT - good relationships matter in situations of power threat JF - Applied psychology : an international review JF - Psychologie appliquée N2 - While previous research underscores the role of leaders in stimulating employee voice behaviour, comparatively little is known about what affects leaders' support for such constructive but potentially threatening employee behaviours. We introduce leader member exchange quality (LMX) as a central predictor of leaders' support for employees' ideas for constructive change. Apart from a general benefit of high LMX for leaders' idea support, we propose that high LMX is particularly critical to leaders' idea support if the idea voiced by an employee constitutes a power threat to the leader. We investigate leaders' attribution of prosocial and egoistic employee intentions as mediators of these effects. Hypotheses were tested in a quasi-experimental vignette study (N = 160), in which leaders evaluated a simulated employee idea, and a field study (N = 133), in which leaders evaluated an idea that had been voiced to them at work. Results show an indirect effect of LMX on leaders' idea support via attributed prosocial intentions but not via attributed egoistic intentions, and a buffering effect of high LMX on the negative effect of power threat on leaders' idea support. Results differed across studies with regard to the main effect of LMX on idea support. KW - proactive personality KW - antecedents KW - behavior KW - consequences KW - metaanalysis KW - model KW - performance KW - supervisors KW - trust KW - work Y1 - 2021 U6 - https://doi.org/10.1111/apps.12245 SN - 0269-994X SN - 1464-0597 VL - 70 IS - 2 SP - 674 EP - 708 PB - Wiley CY - Hoboken ER -