335 results on '"Clark, David W"'
Search Results
102. Malignant Fibrous Histiocytoma of the Head and Neck Region
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Clark, David W., primary, Moore, Brian A., additional, Roberts, Dianna B., additional, and Sturgis, Erich M., additional
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- 2009
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103. Perfect partners: CIM and automation: advanced concepts in hardware design and software systems for material handling yield real payoffs in the factory
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Clark, David W.
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Computer-integrated manufacturing -- Usage ,Materials handling -- Technology application ,Automatic guided vehicles -- Design and construction ,Factories -- Technology application ,Webb Publishing Co. -- Innovations - Published
- 1989
104. Groundwater chemistry and occurrence of arsenic in the Meghna floodplain aquifer, southeastern Bangladesh
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Zahid, Anwar, primary, Hassan, M. Qumrul, additional, Balke, K.-D., additional, Flegr, Matthias, additional, and Clark, David W., additional
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- 2007
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105. Breast cancer metastasis suppressor 1 (BRMS1) inhibits osteopontin transcription by abrogating NF-κB activation
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Samant, Rajeev S, primary, Clark, David W, additional, Fillmore, Rebecca A, additional, Cicek, Muzaffer, additional, Metge, Brandon J, additional, Chandramouli, Kondethimmana H, additional, Chambers, Ann F, additional, Casey, Graham, additional, Welch, Danny R, additional, and Shevde, Lalita A, additional
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- 2007
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106. Variation in digestive efficiency of captive North American river otters (Lontra canadensis) on various diets
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White, Steffany C., primary, Clark, David W., additional, Day, Carrie D., additional, and Sikes, Robert S., additional
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- 2007
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107. Carl Albert: Little Giant of Native America.
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Clark, David W.
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The article focuses on Carl Albert, former Oklahoma Congressman and Speaker of the U.S. House of Representatives who was called as the little giant from little dixie, and his policies that aided the social, economic and political standing of the Native American tribes in Oklahoma.
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- 2015
108. A graphical modeling tool for evaluating nitrogen loading to and nitrate transport in ground water in the mid-Snake region, south-central Idaho
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Clark, David W., primary, Skinner, Kenneth D., additional, and Pollock, David W., additional
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- 2006
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109. The use of a new screw to aid removal of broken interlocking screws
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Stott, Philip M. and Clark, David W.
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- 2006
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110. Synthesis of symmetrically substituted 1,4- bis [(aminoalkyl) amino]-5,8-dimethylanthracene-9,10-diones
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Horn, David E., primary, Leonard, Michael S., additional, Fischl, Amy J., additional, Gray, Maribel, additional, Clark, David W., additional, Averion-Mahlock, Tim, additional, and Sader, Camil N., additional
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- 2000
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111. Diabetic gastroparesis
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Clark, David W., primary and Nowak, Thomas V., additional
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- 1994
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112. Radon in ground water of western Montana
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Clark, David W., primary and Briar, D.W., additional
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- 1993
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113. What is ground water?
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Clark, David W., primary and Briar, David W., additional
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- 1993
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114. Staphylococcus aureus prevalence in allergic fungal rhinosinusitis vs other subsets of chronic rhinosinusitis with nasal polyps.
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Clark, David W., Wenaas, Ashley, Luong, Amber, Citardi, Martin J., and Fakhri, Samer
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Background The pathogenesis of allergic fungal rhinosinusitis (AFRS) is thought to represent an immunological reaction to fungal antigens. Recent studies have implicated superantigens and non-immunoglobulin E (IgE)-mediated mechanisms in the development of AFRS. The objective of this study is to assess the prevalence of Staphylococcus aureus in AFRS vs other subsets of chronic rhinosinusitis with polyps (CRSwNP, also termed non-AFRS). Methods A case series with retrospective review of 19 patients with AFRS and 21 patients with CRSwNP was performed at a tertiary referral center. The diagnosis of AFRS required the presence of defined criteria described by Bent and Kuhn. Bacterial cultures and fungal cultures were analyzed for each group. Results S. aureus was significantly more prevalent in the AFRS group compared with the non-AFRS group (63.2% vs 24.1%, p = 0.005). Conclusion S. aureus has been implicated as a disease modifier in CRSwNP through superantigen-mediated mechanisms. This study demonstrates a higher prevalence of S. aureus in patients with AFRS vs patients with other subsets of CRSwNP (non-AFRS). These results support a potential role for S. aureus in the pathogenesis of AFRS. [ABSTRACT FROM AUTHOR]
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- 2013
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115. First-Choice Antihypertensive Drug Use in the Glasgow Blood Pressure Clinic
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Clark, David W. J., primary, Curzio, Joan L., additional, Howie, Catherine A., additional, and Reid, John L., additional
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- 1990
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116. Effects of Immunosympathectomy on Development of High Blood Pressure in Genetically Hypertensive Rats.
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CLARK, DAVID W. J.
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- 1971
117. Raster Scanned Character Recognition (RSCR).
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MEASUREMENT CONCEPT CORP ROME NY, Clark,David W, Przewlocki,Kathryn Sands, MEASUREMENT CONCEPT CORP ROME NY, Clark,David W, and Przewlocki,Kathryn Sands
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The objective of the RSCR was to design and implement a software system which produces bathymetric depth sounding information for input to a digital data base. Input to the RSCR is raster scanned smooth sheets which consist of handwritten depth soundings. The RSCR system includes software to: (1) isolate smooth sheet hand drafted numeric depth soundings from raster scanned input, (2) provide isolated characters to a character recognition routine, and (3) construct and locate output depth soundings in digital format for subsequent use by the Defense Mapping Agency Hydrographic/Topographic Center (DMAHTC). The Hand-printed Symbol Recognition (HSR) software developed by computer Sciences Corp and the Naval Ocean Research and Development Activity (NORDA) is the character recognition routine used. This report documents all of the above mentioned capabilities except the HSR software itself which has been documented separately by CSC and NORDA.
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- 1981
118. Publisher Correction: Parent of origin genetic effects on methylation in humans are common and influence complex trait variation.
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Zeng, Yanni, Amador, Carmen, Xia, Charley, Marioni, Riccardo, Sproul, Duncan, Walker, Rosie M., Morris, Stewart W., Bretherick, Andrew, Canela-Xandri, Oriol, Boutin, Thibaud S., Clark, David W., Campbell, Archie, Rawlik, Konrad, Hayward, Caroline, Nagy, Reka, Tenesa, Albert, Porteous, David J., Wilson, James F., Deary, Ian J., and Evans, Kathryn L.
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In the original version of this Article, the legend in the upper panel of Figure 2 incorrectly read 'paternal imprinting' and should have read 'maternal imprinting'. This has been corrected in both the PDF and HTML versions of the Article. [ABSTRACT FROM AUTHOR]
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- 2019
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119. Parent of origin genetic effects on methylation in humans are common and influence complex trait variation.
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Zeng, Yanni, Amador, Carmen, Xia, Charley, Marioni, Riccardo, Sproul, Duncan, Walker, Rosie M., Morris, Stewart W., Bretherick, Andrew, Canela-Xandri, Oriol, Boutin, Thibaud S., Clark, David W., Campbell, Archie, Rawlik, Konrad, Hayward, Caroline, Nagy, Reka, Tenesa, Albert, Porteous, David J., Wilson, James F., Deary, Ian J., and Evans, Kathryn L.
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Parent-of-origin effects (POE) exist when there is differential expression of alleles inherited from the two parents. A genome-wide scan for POE on DNA methylation at 639,238 CpGs in 5,101 individuals identifies 733 independent methylation CpGs potentially influenced by POE at a false discovery rate ≤ 0.05 of which 331 had not previously been identified. Cis and trans methylation quantitative trait loci (mQTL) regulate methylation variation through POE at 54% (399/733) of the identified POE-influenced CpGs. The combined results provide strong evidence for previously unidentified POE-influenced CpGs at 171 independent loci. Methylation variation at 14 of the POE-influenced CpGs is associated with multiple metabolic traits. A phenome-wide association analysis using the POE mQTL SNPs identifies a previously unidentified imprinted locus associated with waist circumference. These results provide a high resolution population-level map for POE on DNA methylation sites, their local and distant regulators and potential consequences for complex traits. Parent-of-origin effects (POE) are observed when there are different effects from alleles inherited from the two parents on phenotypic measures. Here, Zeng et al. study POE on DNA methylation in 5,101 individuals and identify genetic variants that associate with methylation variation via POE and their potential phenotypic consequences. [ABSTRACT FROM AUTHOR]
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- 2019
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120. Handprinted Character Recognition Techniques.
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COMPUTER SYMBOLIC INC ROME NY, Clark, David W., Connell, David B., Dimeo, Michael P., Opitz, Bruce K., Sammon, John W., Jr, COMPUTER SYMBOLIC INC ROME NY, Clark, David W., Connell, David B., Dimeo, Michael P., Opitz, Bruce K., and Sammon, John W., Jr
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The report describes a set of experiments which have led to the design of logic for the automatic machine recognition of unconstrained handprinted alpha and numeric characters at correct recognition rates in excess of 99% (without rejection). (Author)
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- 1970
121. Feature Definition and Extraction.
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NCS COMPUTING CORP ROME NY COMPUTER SYMBOLIC DIV, Opitz, Bruce K., Clark, David W., Evans, Edward A., Sanders, John H., Sammon, John W., Jr, NCS COMPUTING CORP ROME NY COMPUTER SYMBOLIC DIV, Opitz, Bruce K., Clark, David W., Evans, Edward A., Sanders, John H., and Sammon, John W., Jr
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The report describes a systems software design for an on-line, interactive, graphics-oriented computer system which, when implemented, will be used as a research tool for the design, extraction and evaluation of pattern recognition features. In particular it will be used for the automatic classification of objects contained in two-dimensional imagery. The system has been designed to complement RADC's On-Line Pattern Analysis and Recognition System (OLPARS). (Author)
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- 1970
122. PROGRAMMING PACKAGE FOR ON-LINE PATTERN RECOGNITION.
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COMPUTER SYMBOLIC INC ROME N Y, Connell,David B., Clark,David W., Opitz,Bruce K., Martin,Patrick J., Novell,Monroe, COMPUTER SYMBOLIC INC ROME N Y, Connell,David B., Clark,David W., Opitz,Bruce K., Martin,Patrick J., and Novell,Monroe
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The report describes a programming package for on-line pattern recognition. The present OLPARS capability is implemented on the BR-85/CDC-1604B computing system. The first two sections of the report are relative to this implementation. Section 1 is a User's Manual for the Distribution Free Module, and represents a description of the largest single functional program within the OLPARS system. It is through the use of the Distribution Free Logic Design (DFLD) subsystem that the OLPARS user constructs the logic to solve a pattern classification problem. This subsystem, via mathematical/graphical techniques, provides the user with the capability of fitting decision logic to the actual structure of the data. Section 2 is the Distribution Free Module Programmers Guide. The guide provides a system program and subroutine cross reference listing, in effect providing the user with a description of the functions performed by each of the routines within the Distribution Free Subsystem. Further, the filing system considerations are presented as is a user's guide for the filing system overlay. (Author)
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- 1970
123. Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity
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Hofer, Edith, Schmidt, Reinhold, Ikram, M. Arfan, Lumley, Thomas, Wilson, James G., Nagy, Reka, Graff, Mariaelisa, Boomsma, Dorret I., Proitsi, Petroula, Barnes, Catriona L. K., Whitfield, John B., McDaid, Aaron F., Ciullo, Marina, Kuh, Diana, Rivadeneira, Fernando, Uitterlinden, André G., Saba, Yasaman, Kiemeney, Lambertus, Kutalik, Zoltán, Tajuddin, Salman M., Kentistou, Katherine A., Galesloot, Tessel E., Biino, Ginevra, Milani, Lili, Wilson, James F., Franceschini, Nora, Van Rooij, Frank J. A., Hougaard, David M., Hurme, Mikko A., Zhao, Wei, Lindenberger, Ulman, Gordon, Scott D., Van Duijn, Cornelia M., Schmidt, Helena, Nutile, Teresa, Børglum, Anders D., Pirastu, Nicola, Vermeulen, Sita H., Metspalu, Andres, Ford, Ian, Fuchsberger, Christian, Schraut, Katharina E., North, Kari E., Becker, Diane M., Werge, Thomas, Boerwinkle, Eric, Vollenweider, Peter, Smith, Blair H., Payton, Antony, Wong, Andrew, Kardia, Sharon L. R., Abdellaoui, Abdel, Fischer, Krista, Hottenga, Jouke-Jan, Van Der Spek, Ashley, Pendleton, Neil, Joshi, Peter K., Mägi, Reedik, Yanek, Lisa R., Chasman, Daniel, Bielak, Lawrence F., Giulianini, Franco, Verbeek, André L., Sotoodehnia, Nona, Lehtimäki, Terho, Bertram, Lars, Peyser, Patricia A., Martin, Nicholas G., Timmers, Paul R. H. J., Zonderman, Alan B., Ollier, William E. R., Raffield, Laura, Lange, Leslie A., Shen, Xia, Lill, Christina M., Concas, Maria Pina, Pramstaller, Peter P., Jylhä, Marja, Steinhagen-Thiessen, Elisabeth, Evans, Michele K., Amin, Najaf, Medland, Sarah E., Hingorani, Aroon, Gögele, Martin, Pirastu, Mario, Trompet, Stella, Smith, Jennifer A., Gialluisi, Alessandro, Jukema, J. Wouter, Ridker, Paul M., Gandin, Ilaria, Boutin, Thibaud S., Campbell, Archie, Medina-Gomez, Carolina, Demuth, Ilja, Faul, Jessica D., Murgia, Federico, Clark, David W., Marques-Vidal, Pedro, Weir, David R., Hansen, Thomas Folkmann, Sattar, Naveed, Hayward, Caroline, Esko, Tonu, Seppälä, Ilkka, Campbell, Harry, Wang, Yunpeng, Ruggiero, Daniela, Demerath, Ellen W., Slagboom, P. Eline, Bartz, Traci M., Ligthart, Lannie, and Psaty, Bruce M.
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2. Zero hunger ,3. Good health - Abstract
Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents' survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated. We suggest that the effect of education on lifespan is principally mediated through smoking while the effect of obesity appears to act via CAD. Using instrumental variables, we suggest that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan.Variability in human longevity is genetically influenced. Using genetic data of parental lifespan, the authors identify associations at HLA-DQA/DRB1 and LPA and find that genetic variants that increase educational attainment have a positive effect on lifespan whereas increasing BMI negatively affects lifespan.
124. Associations of autozygosity with a broad range of human phenotypes
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Clark, David W, Okada, Yukinori, Moore, Kristjan HS, Mason, Dan, Pirastu, Nicola, Gandin, Ilaria, Mattsson, Hannele, Barnes, Catriona LK, Lin, Kuang, Zhao, Jing Hua, Deelen, Patrick, Rohde, Rebecca, Schurmann, Claudia, Guo, Xiuqing, Giulianini, Franco, Zhang, Weihua, Medina-Gomez, Carolina, Karlsson, Robert, Bao, Yanchun, Bartz, Traci M, Baumbach, Clemens, Biino, Ginevra, Bixley, Matthew J, Brumat, Marco, Chai, Jin-Fang, Corre, Tanguy, Cousminer, Diana L, Dekker, Annelot M, Eccles, David A, Van Eijk, Kristel R, Fuchsberger, Christian, Gao, He, Germain, Marine, Gordon, Scott D, De Haan, Hugoline G, Harris, Sarah E, Hofer, Edith, Huerta-Chagoya, Alicia, Igartua, Catherine, Jansen, Iris E, Jia, Yucheng, Kacprowski, Tim, Karlsson, Torgny, Kleber, Marcus E, Li, Shengchao Alfred, Li-Gao, Ruifang, Mahajan, Anubha, Matsuda, Koichi, Meidtner, Karina, Meng, Weihua, Montasser, May E, Van Der Most, Peter J, Munz, Matthias, Nutile, Teresa, Palviainen, Teemu, Prasad, Gauri, Prasad, Rashmi B, Priyanka, Tallapragada Divya Sri, Rizzi, Federica, Salvi, Erika, Sapkota, Bishwa R, Shriner, Daniel, Skotte, Line, Smart, Melissa C, Smith, Albert Vernon, Van Der Spek, Ashley, Spracklen, Cassandra N, Strawbridge, Rona J, Tajuddin, Salman M, Trompet, Stella, Turman, Constance, Verweij, Niek, Viberti, Clara, Wang, Lihua, Warren, Helen R, Wootton, Robyn E, Yanek, Lisa R, Yao, Jie, Yousri, Noha A, Zhao, Wei, Adeyemo, Adebowale A, Afaq, Saima, Aguilar-Salinas, Carlos Alberto, Akiyama, Masato, Albert, Matthew L, Allison, Matthew A, Alver, Maris, Aung, Tin, Azizi, Fereidoun, Bentley, Amy R, Boeing, Heiner, Boerwinkle, Eric, Borja, Judith B, De Borst, Gert J, Bottinger, Erwin P, Broer, Linda, Campbell, Harry, Chanock, Stephen, Chee, Miao-Li, Chen, Guanjie, Chen, Yii-Der I, Chen, Zhengming, Chiu, Yen-Feng, Cocca, Massimiliano, Collins, Francis S, Concas, Maria Pina, Corley, Janie, Cugliari, Giovanni, Van Dam, Rob M, Damulina, Anna, Daneshpour, Maryam S, Day, Felix R, Delgado, Graciela E, Dhana, Klodian, Doney, Alexander SF, Dörr, Marcus, Doumatey, Ayo P, Dzimiri, Nduna, Ebenesersdóttir, S Sunna, Elliott, Joshua, Elliott, Paul, Ewert, Ralf, Felix, Janine F, Fischer, Krista, Freedman, Barry I, Girotto, Giorgia, Goel, Anuj, Gögele, Martin, Goodarzi, Mark O, Graff, Mariaelisa, Granot-Hershkovitz, Einat, Grodstein, Francine, Guarrera, Simonetta, Gudbjartsson, Daniel F, Guity, Kamran, Gunnarsson, Bjarni, Guo, Yu, Hagenaars, Saskia P, Haiman, Christopher A, Halevy, Avner, Harris, Tamara B, Hedayati, Mehdi, Van Heel, David A, Hirata, Makoto, Höfer, Imo, Hsiung, Chao Agnes, Huang, Jinyan, Hung, Yi-Jen, Ikram, M Arfan, Jagadeesan, Anuradha, Jousilahti, Pekka, Kamatani, Yoichiro, Kanai, Masahiro, Kerrison, Nicola D, Kessler, Thorsten, Khaw, Kay-Tee, Khor, Chiea Chuen, De Kleijn, Dominique PV, Koh, Woon-Puay, Kolcic, Ivana, Kraft, Peter, Krämer, Bernhard K, Kutalik, Zoltán, Kuusisto, Johanna, Langenberg, Claudia, Launer, Lenore J, Lawlor, Deborah A, Lee, I-Te, Lee, Wen-Jane, Lerch, Markus M, Li, Liming, Liu, Jianjun, Loh, Marie, London, Stephanie J, Loomis, Stephanie, Lu, Yingchang, Luan, Jian'an, Mägi, Reedik, Manichaikul, Ani W, Manunta, Paolo, Másson, Gísli, Matoba, Nana, Mei, Xue W, Meisinger, Christa, Meitinger, Thomas, Mezzavilla, Massimo, Milani, Lili, Millwood, Iona Y, Momozawa, Yukihide, Moore, Amy, Morange, Pierre-Emmanuel, Moreno-Macías, Hortensia, Mori, Trevor A, Morrison, Alanna C, Muka, Taulant, Murakami, Yoshinori, Murray, Alison D, De Mutsert, Renée, Mychaleckyj, Josyf C, Nalls, Mike A, Nauck, Matthias, Neville, Matt J, Nolte, Ilja M, Ong, Ken K, Orozco, Lorena, Padmanabhan, Sandosh, Pálsson, Gunnar, Pankow, James S, Pattaro, Cristian, Pattie, Alison, Polasek, Ozren, Poulter, Neil, Pramstaller, Peter P, Quintana-Murci, Lluis, Räikkönen, Katri, Ralhan, Sarju, Rao, Dabeeru C, Van Rheenen, Wouter, Rich, Stephen S, Ridker, Paul M, Rietveld, Cornelius A, Robino, Antonietta, Van Rooij, Frank JA, Ruggiero, Daniela, Saba, Yasaman, Sabanayagam, Charumathi, Sabater-Lleal, Maria, Sala, Cinzia Felicita, Salomaa, Veikko, Sandow, Kevin, Schmidt, Helena, Scott, Laura J, Scott, William R, Sedaghati-Khayat, Bahareh, Sennblad, Bengt, Van Setten, Jessica, Sever, Peter J, Sheu, Wayne H-H, Shi, Yuan, Shrestha, Smeeta, Shukla, Sharvari Rahul, Sigurdsson, Jon K, Sikka, Timo Tonis, Singh, Jai Rup, Smith, Blair H, Stančáková, Alena, Stanton, Alice, Starr, John M, Stefansdottir, Lilja, Straker, Leon, Sulem, Patrick, Sveinbjornsson, Gardar, Swertz, Morris A, Taylor, Adele M, Taylor, Kent D, Terzikhan, Natalie, Tham, Yih-Chung, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tillander, Annika, Tracy, Russell P, Tusié-Luna, Teresa, Tzoulaki, Ioanna, Vaccargiu, Simona, Vangipurapu, Jagadish, Veldink, Jan H, Vitart, Veronique, Völker, Uwe, Vuoksimaa, Eero, Wakil, Salma M, Waldenberger, Melanie, Wander, Gurpreet S, Wang, Ya Xing, Wareham, Nicholas J, Wild, Sarah, Yajnik, Chittaranjan S, Yuan, Jian-Min, Zeng, Lingyao, Zhang, Liang, Zhou, Jie, Amin, Najaf, Asselbergs, Folkert W, Bakker, Stephan JL, Becker, Diane M, Lehne, Benjamin, Bennett, David A, Van Den Berg, Leonard H, Berndt, Sonja I, Bharadwaj, Dwaipayan, Bielak, Lawrence F, Bochud, Murielle, Boehnke, Mike, Bouchard, Claude, Bradfield, Jonathan P, Brody, Jennifer A, Campbell, Archie, Carmi, Shai, Caulfield, Mark J, Cesarini, David, Chambers, John C, Chandak, Giriraj Ratan, Cheng, Ching-Yu, Ciullo, Marina, Cornelis, Marilyn, Cusi, Daniele, Smith, George Davey, Deary, Ian J, Dorajoo, Rajkumar, Van Duijn, Cornelia M, Ellinghaus, David, Erdmann, Jeanette, Eriksson, Johan G, Evangelou, Evangelos, Evans, Michele K, Faul, Jessica D, Feenstra, Bjarke, Feitosa, Mary, Foisy, Sylvain, Franke, Andre, Friedlander, Yechiel, Gasparini, Paolo, Gieger, Christian, Gonzalez, Clicerio, Goyette, Philippe, Grant, Struan FA, Griffiths, Lyn R, Groop, Leif, Gudnason, Vilmundur, Gyllensten, Ulf, Hakonarson, Hakon, Hamsten, Anders, Van Der Harst, Pim, Heng, Chew-Kiat, Hicks, Andrew A, Hochner, Hagit, Huikuri, Heikki, Hunt, Steven C, Jaddoe, Vincent WV, De Jager, Philip L, Johannesson, Magnus, Johansson, Åsa, Jonas, Jost B, Jukema, J Wouter, Junttila, Juhani, Kaprio, Jaakko, Kardia, Sharon LR, Karpe, Fredrik, Kumari, Meena, Laakso, Markku, Van Der Laan, Sander W, Lahti, Jari, Laudes, Matthias, Lea, Rodney A, Lieb, Wolfgang, Lumley, Thomas, Martin, Nicholas G, März, Winfried, Matullo, Giuseppe, McCarthy, Mark I, Medland, Sarah E, Merriman, Tony R, Metspalu, Andres, Meyer, Brian F, Mohlke, Karen L, Montgomery, Grant W, Mook-Kanamori, Dennis, Munroe, Patricia B, North, Kari E, Nyholt, Dale R, O'connell, Jeffery R, Ober, Carole, Oldehinkel, Albertine J, Palmas, Walter, Palmer, Colin, Pasterkamp, Gerard G, Patin, Etienne, Pennell, Craig E, Perusse, Louis, Peyser, Patricia A, Pirastu, Mario, Polderman, Tinca JC, Porteous, David J, Posthuma, Danielle, Psaty, Bruce M, Rioux, John D, Rivadeneira, Fernando, Rotimi, Charles, Rotter, Jerome I, Rudan, Igor, Den Ruijter, Hester M, Sanghera, Dharambir K, Sattar, Naveed, Schmidt, Reinhold, Schulze, Matthias B, Schunkert, Heribert, Scott, Robert A, Shuldiner, Alan R, Sim, Xueling, Small, Neil, Smith, Jennifer A, Sotoodehnia, Nona, Tai, E-Shyong, Teumer, Alexander, Timpson, Nicholas J, Toniolo, Daniela, Tregouet, David-Alexandre, Tuomi, Tiinamaija, Vollenweider, Peter, Wang, Carol A, Weir, David R, Whitfield, John B, Wijmenga, Cisca, Wong, Tien-Yin, Wright, John, Yang, Jingyun, Yu, Lei, Zemel, Babette S, Zonderman, Alan B, Perola, Markus, Magnusson, Patrik KE, Uitterlinden, André G, Kooner, Jaspal S, Chasman, Daniel I, Loos, Ruth JF, Franceschini, Nora, Franke, Lude, Haley, Chris S, Hayward, Caroline, Walters, Robin G, Perry, John RB, Esko, Tōnu, Helgason, Agnar, Stefansson, Kari, Joshi, Peter K, Kubo, Michiaki, and Wilson, James F
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Consanguinity ,Cognition ,Fertility ,Inbreeding Depression ,Risk-Taking ,Haplotypes ,Health Status ,Homozygote ,Body Size ,Humans ,Alleles ,3. Good health - Abstract
In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
125. Associations of autozygosity with a broad range of human phenotypes
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Clark, David W, Okada, Yukinori, Moore, Kristjan H S, Mason, Dan, Pirastu, Nicola, Gandin, Ilaria, Mattsson, Hannele, Barnes, Catriona L K, Lin, Kuang, Zhao, Jing Hua, Deelen, Patrick, Rohde, Rebecca, Schurmann, Claudia, Guo, Xiuqing, Giulianini, Franco, Zhang, Weihua, Medina-Gomez, Carolina, Karlsson, Robert, Bao, Yanchun, Bartz, Traci M, Baumbach, Clemens, Biino, Ginevra, Bixley, Matthew J, Brumat, Marco, Chai, Jin-Fang, Corre, Tanguy, Cousminer, Diana L, Dekker, Annelot M, Eccles, David A, Van Eijk, Kristel R, Fuchsberger, Christian, Gao, He, Germain, Marine, Gordon, Scott D, De Haan, Hugoline G, Harris, Sarah E, Hofer, Edith, Huerta-Chagoya, Alicia, Igartua, Catherine, Jansen, Iris E, Jia, Yucheng, Kacprowski, Tim, Karlsson, Torgny, Kleber, Marcus E, Li, Shengchao Alfred, Li-Gao, Ruifang, Mahajan, Anubha, Matsuda, Koichi, Meidtner, Karina, Meng, Weihua, Montasser, May E, Van Der Most, Peter J, Munz, Matthias, Nutile, Teresa, Palviainen, Teemu, Prasad, Gauri, Prasad, Rashmi B, Priyanka, Tallapragada Divya Sri, Rizzi, Federica, Salvi, Erika, Sapkota, Bishwa R, Shriner, Daniel, Skotte, Line, Smart, Melissa C, Smith, Albert Vernon, Van Der Spek, Ashley, Spracklen, Cassandra N, Strawbridge, Rona J, Tajuddin, Salman M, Trompet, Stella, Turman, Constance, Verweij, Niek, Viberti, Clara, Wang, Lihua, Warren, Helen R, Wootton, Robyn E, Yanek, Lisa R, Yao, Jie, Yousri, Noha A, Zhao, Wei, Adeyemo, Adebowale A, Afaq, Saima, Aguilar-Salinas, Carlos Alberto, Akiyama, Masato, Albert, Matthew L, Allison, Matthew A, Alver, Maris, Aung, Tin, Azizi, Fereidoun, Bentley, Amy R, Boeing, Heiner, Boerwinkle, Eric, Borja, Judith B, De Borst, Gert J, Bottinger, Erwin P, Broer, Linda, Campbell, Harry, Chanock, Stephen, Chee, Miao-Li, Chen, Guanjie, Chen, Yii-Der I, Chen, Zhengming, Chiu, Yen-Feng, Cocca, Massimiliano, Collins, Francis S, Concas, Maria Pina, Corley, Janie, Cugliari, Giovanni, Van Dam, Rob M, Damulina, Anna, Daneshpour, Maryam S, Day, Felix R, Delgado, Graciela E, Dhana, Klodian, Doney, Alexander S F, Dörr, Marcus, Doumatey, Ayo P, Dzimiri, Nduna, Ebenesersdóttir, S Sunna, Elliott, Joshua, Elliott, Paul, Ewert, Ralf, Felix, Janine F, Fischer, Krista, Freedman, Barry I, Girotto, Giorgia, Goel, Anuj, Gögele, Martin, Goodarzi, Mark O, Graff, Mariaelisa, Granot-Hershkovitz, Einat, Grodstein, Francine, Guarrera, Simonetta, Gudbjartsson, Daniel F, Guity, Kamran, Gunnarsson, Bjarni, Guo, Yu, Hagenaars, Saskia P, Haiman, Christopher A, Halevy, Avner, Harris, Tamara B, Hedayati, Mehdi, Van Heel, David A, Hirata, Makoto, Höfer, Imo, Hsiung, Chao Agnes, Huang, Jinyan, Hung, Yi-Jen, Ikram, M Arfan, Jagadeesan, Anuradha, Jousilahti, Pekka, Kamatani, Yoichiro, Kanai, Masahiro, Kerrison, Nicola D, Kessler, Thorsten, Khaw, Kay-Tee, Khor, Chiea Chuen, De Kleijn, Dominique P V, Koh, Woon-Puay, Kolcic, Ivana, Kraft, Peter, Krämer, Bernhard K, Kutalik, Zoltán, Kuusisto, Johanna, Langenberg, Claudia, Launer, Lenore J, Lawlor, Deborah A, Lee, I-Te, Lee, Wen-Jane, Lerch, Markus M, Li, Liming, Liu, Jianjun, Loh, Marie, London, Stephanie J, Loomis, Stephanie, Lu, Yingchang, Luan, Jian'an, Mägi, Reedik, Manichaikul, Ani W, Manunta, Paolo, Másson, Gísli, Matoba, Nana, Mei, Xue W, Meisinger, Christa, Meitinger, Thomas, Mezzavilla, Massimo, Milani, Lili, Millwood, Iona Y, Momozawa, Yukihide, Moore, Amy, Morange, Pierre-Emmanuel, Moreno-Macías, Hortensia, Mori, Trevor A, Morrison, Alanna C, Muka, Taulant, Murakami, Yoshinori, Murray, Alison D, De Mutsert, Renée, Mychaleckyj, Josyf C, Nalls, Mike A, Nauck, Matthias, Neville, Matt J, Nolte, Ilja M, Ong, Ken K, Orozco, Lorena, Padmanabhan, Sandosh, Pálsson, Gunnar, Pankow, James S, Pattaro, Cristian, Pattie, Alison, Polasek, Ozren, Poulter, Neil, Pramstaller, Peter P, Quintana-Murci, Lluis, Räikkönen, Katri, Ralhan, Sarju, Rao, Dabeeru C, Van Rheenen, Wouter, Rich, Stephen S, Ridker, Paul M, Rietveld, Cornelius A, Robino, Antonietta, Van Rooij, Frank J A, Ruggiero, Daniela, Saba, Yasaman, Sabanayagam, Charumathi, Sabater-Lleal, Maria, Sala, Cinzia Felicita, Salomaa, Veikko, Sandow, Kevin, Schmidt, Helena, Scott, Laura J, Scott, William R, Sedaghati-Khayat, Bahareh, Sennblad, Bengt, Van Setten, Jessica, Sever, Peter J, Sheu, Wayne H-H, Shi, Yuan, Shrestha, Smeeta, Shukla, Sharvari Rahul, Sigurdsson, Jon K, Sikka, Timo Tonis, Singh, Jai Rup, Smith, Blair H, Stančáková, Alena, Stanton, Alice, Starr, John M, Stefansdottir, Lilja, Straker, Leon, Sulem, Patrick, Sveinbjornsson, Gardar, Swertz, Morris A, Taylor, Adele M, Taylor, Kent D, Terzikhan, Natalie, Tham, Yih-Chung, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tillander, Annika, Tracy, Russell P, Tusié-Luna, Teresa, Tzoulaki, Ioanna, Vaccargiu, Simona, Vangipurapu, Jagadish, Veldink, Jan H, Vitart, Veronique, Völker, Uwe, Vuoksimaa, Eero, Wakil, Salma M, Waldenberger, Melanie, Wander, Gurpreet S, Wang, Ya Xing, Wareham, Nicholas J, Wild, Sarah, Yajnik, Chittaranjan S, Yuan, Jian-Min, Zeng, Lingyao, Zhang, Liang, Zhou, Jie, Amin, Najaf, Asselbergs, Folkert W, Bakker, Stephan J L, Becker, Diane M, Lehne, Benjamin, Bennett, David A, Van Den Berg, Leonard H, Berndt, Sonja I, Bharadwaj, Dwaipayan, Bielak, Lawrence F, Bochud, Murielle, Boehnke, Mike, Bouchard, Claude, Bradfield, Jonathan P, Brody, Jennifer A, Campbell, Archie, Carmi, Shai, Caulfield, Mark J, Cesarini, David, Chambers, John C, Chandak, Giriraj Ratan, Cheng, Ching-Yu, Ciullo, Marina, Cornelis, Marilyn, Cusi, Daniele, Smith, George Davey, Deary, Ian J, Dorajoo, Rajkumar, Van Duijn, Cornelia M, Ellinghaus, David, Erdmann, Jeanette, Eriksson, Johan G, Evangelou, Evangelos, Evans, Michele K, Faul, Jessica D, Feenstra, Bjarke, Feitosa, Mary, Foisy, Sylvain, Franke, Andre, Friedlander, Yechiel, Gasparini, Paolo, Gieger, Christian, Gonzalez, Clicerio, Goyette, Philippe, Grant, Struan F A, Griffiths, Lyn R, Groop, Leif, Gudnason, Vilmundur, Gyllensten, Ulf, Hakonarson, Hakon, Hamsten, Anders, Van Der Harst, Pim, Heng, Chew-Kiat, Hicks, Andrew A, Hochner, Hagit, Huikuri, Heikki, Hunt, Steven C, Jaddoe, Vincent W V, De Jager, Philip L, Johannesson, Magnus, Johansson, Åsa, Jonas, Jost B, Jukema, J Wouter, Junttila, Juhani, Kaprio, Jaakko, Kardia, Sharon L R, Karpe, Fredrik, Kumari, Meena, Laakso, Markku, Van Der Laan, Sander W, Lahti, Jari, Laudes, Matthias, Lea, Rodney A, Lieb, Wolfgang, Lumley, Thomas, Martin, Nicholas G, März, Winfried, Matullo, Giuseppe, McCarthy, Mark I, Medland, Sarah E, Merriman, Tony R, Metspalu, Andres, Meyer, Brian F, Mohlke, Karen L, Montgomery, Grant W, Mook-Kanamori, Dennis, Munroe, Patricia B, North, Kari E, Nyholt, Dale R, O'connell, Jeffery R, Ober, Carole, Oldehinkel, Albertine J, Palmas, Walter, Palmer, Colin, Pasterkamp, Gerard G, Patin, Etienne, Pennell, Craig E, Perusse, Louis, Peyser, Patricia A, Pirastu, Mario, Polderman, Tinca J C, Porteous, David J, Posthuma, Danielle, Psaty, Bruce M, Rioux, John D, Rivadeneira, Fernando, Rotimi, Charles, Rotter, Jerome I, Rudan, Igor, Den Ruijter, Hester M, Sanghera, Dharambir K, Sattar, Naveed, Schmidt, Reinhold, Schulze, Matthias B, Schunkert, Heribert, Scott, Robert A, Shuldiner, Alan R, Sim, Xueling, Small, Neil, Smith, Jennifer A, Sotoodehnia, Nona, Tai, E-Shyong, Teumer, Alexander, Timpson, Nicholas J, Toniolo, Daniela, Tregouet, David-Alexandre, Tuomi, Tiinamaija, Vollenweider, Peter, Wang, Carol A, Weir, David R, Whitfield, John B, Wijmenga, Cisca, Wong, Tien-Yin, Wright, John, Yang, Jingyun, Yu, Lei, Zemel, Babette S, Zonderman, Alan B, Perola, Markus, Magnusson, Patrik K E, Uitterlinden, André G, Kooner, Jaspal S, Chasman, Daniel I, Loos, Ruth J F, Franceschini, Nora, Franke, Lude, Haley, Chris S, Hayward, Caroline, Walters, Robin G, Perry, John R B, Esko, Tōnu, Helgason, Agnar, Stefansson, Kari, Joshi, Peter K, Kubo, Michiaki, and Wilson, James F
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610 Medicine & health ,360 Social problems & social services ,3. Good health - Abstract
In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p
126. Associations of autozygosity with a broad range of human phenotypes
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Clark, David W, Okada, Yukinori, Moore, Kristjan H S, Mason, Dan, Pirastu, Nicola, Gandin, Ilaria, Mattsson, Hannele, Barnes, Catriona L K, Lin, Kuang, Zhao, Jing Hua, Deelen, Patrick, Rohde, Rebecca, Schurmann, Claudia, Guo, Xiuqing, Giulianini, Franco, Zhang, Weihua, Medina-Gomez, Carolina, Karlsson, Robert, Bao, Yanchun, Bartz, Traci M, Baumbach, Clemens, Biino, Ginevra, Bixley, Matthew J, Brumat, Marco, Chai, Jin-Fang, Corre, Tanguy, Cousminer, Diana L, Dekker, Annelot M, Eccles, David A, Van Eijk, Kristel R, Fuchsberger, Christian, Gao, He, Germain, Marine, Gordon, Scott D, De Haan, Hugoline G, Harris, Sarah E, Hofer, Edith, Huerta-Chagoya, Alicia, Igartua, Catherine, Jansen, Iris E, Jia, Yucheng, Kacprowski, Tim, Karlsson, Torgny, Kleber, Marcus E, Li, Shengchao Alfred, Li-Gao, Ruifang, Mahajan, Anubha, Matsuda, Koichi, Meidtner, Karina, Meng, Weihua, Montasser, May E, Van Der Most, Peter J, Munz, Matthias, Nutile, Teresa, Palviainen, Teemu, Prasad, Gauri, Prasad, Rashmi B, Priyanka, Tallapragada Divya Sri, Rizzi, Federica, Salvi, Erika, Sapkota, Bishwa R, Shriner, Daniel, Skotte, Line, Smart, Melissa C, Smith, Albert Vernon, Van Der Spek, Ashley, Spracklen, Cassandra N, Strawbridge, Rona J, Tajuddin, Salman M, Trompet, Stella, Turman, Constance, Verweij, Niek, Viberti, Clara, Wang, Lihua, Warren, Helen R, Wootton, Robyn E, Yanek, Lisa R, Yao, Jie, Yousri, Noha A, Zhao, Wei, Adeyemo, Adebowale A, Afaq, Saima, Aguilar-Salinas, Carlos Alberto, Akiyama, Masato, Albert, Matthew L, Allison, Matthew A, Alver, Maris, Aung, Tin, Azizi, Fereidoun, Bentley, Amy R, Boeing, Heiner, Boerwinkle, Eric, Borja, Judith B, De Borst, Gert J, Bottinger, Erwin P, Broer, Linda, Campbell, Harry, Chanock, Stephen, Chee, Miao-Li, Chen, Guanjie, Chen, Yii-Der I, Chen, Zhengming, Chiu, Yen-Feng, Cocca, Massimiliano, Collins, Francis S, Concas, Maria Pina, Corley, Janie, Cugliari, Giovanni, Van Dam, Rob M, Damulina, Anna, Daneshpour, Maryam S, Day, Felix R, Delgado, Graciela E, Dhana, Klodian, Doney, Alexander S F, Dörr, Marcus, Doumatey, Ayo P, Dzimiri, Nduna, Ebenesersdóttir, S Sunna, Elliott, Joshua, Elliott, Paul, Ewert, Ralf, Felix, Janine F, Fischer, Krista, Freedman, Barry I, Girotto, Giorgia, Goel, Anuj, Gögele, Martin, Goodarzi, Mark O, Graff, Mariaelisa, Granot-Hershkovitz, Einat, Grodstein, Francine, Guarrera, Simonetta, Gudbjartsson, Daniel F, Guity, Kamran, Gunnarsson, Bjarni, Guo, Yu, Hagenaars, Saskia P, Haiman, Christopher A, Halevy, Avner, Harris, Tamara B, Hedayati, Mehdi, Van Heel, David A, Hirata, Makoto, Höfer, Imo, Hsiung, Chao Agnes, Huang, Jinyan, Hung, Yi-Jen, Ikram, M Arfan, Jagadeesan, Anuradha, Jousilahti, Pekka, Kamatani, Yoichiro, Kanai, Masahiro, Kerrison, Nicola D, Kessler, Thorsten, Khaw, Kay-Tee, Khor, Chiea Chuen, De Kleijn, Dominique P V, Koh, Woon-Puay, Kolcic, Ivana, Kraft, Peter, Krämer, Bernhard K, Kutalik, Zoltán, Kuusisto, Johanna, Langenberg, Claudia, Launer, Lenore J, Lawlor, Deborah A, Lee, I-Te, Lee, Wen-Jane, Lerch, Markus M, Li, Liming, Liu, Jianjun, Loh, Marie, London, Stephanie J, Loomis, Stephanie, Lu, Yingchang, Luan, Jian’an, Mägi, Reedik, Manichaikul, Ani W, Manunta, Paolo, Másson, Gísli, Matoba, Nana, Mei, Xue W, Meisinger, Christa, Meitinger, Thomas, Mezzavilla, Massimo, Milani, Lili, Millwood, Iona Y, Momozawa, Yukihide, Moore, Amy, Morange, Pierre-Emmanuel, Moreno-Macías, Hortensia, Mori, Trevor A, Morrison, Alanna C, Muka, Taulant, Murakami, Yoshinori, Murray, Alison D, De Mutsert, Renée, Mychaleckyj, Josyf C, Nalls, Mike A, Nauck, Matthias, Neville, Matt J, Nolte, Ilja M, Ong, Ken K, Orozco, Lorena, Padmanabhan, Sandosh, Pálsson, Gunnar, Pankow, James S, Pattaro, Cristian, Pattie, Alison, Polasek, Ozren, Poulter, Neil, Pramstaller, Peter P, Quintana-Murci, Lluis, Räikkönen, Katri, Ralhan, Sarju, Rao, Dabeeru C, Van Rheenen, Wouter, Rich, Stephen S, Ridker, Paul M, Rietveld, Cornelius A, Robino, Antonietta, Van Rooij, Frank J A, Ruggiero, Daniela, Saba, Yasaman, Sabanayagam, Charumathi, Sabater-Lleal, Maria, Sala, Cinzia Felicita, Salomaa, Veikko, Sandow, Kevin, Schmidt, Helena, Scott, Laura J, Scott, William R, Sedaghati-Khayat, Bahareh, Sennblad, Bengt, Van Setten, Jessica, Sever, Peter J, Sheu, Wayne H-H, Shi, Yuan, Shrestha, Smeeta, Shukla, Sharvari Rahul, Sigurdsson, Jon K, Sikka, Timo Tonis, Singh, Jai Rup, Smith, Blair H, Stančáková, Alena, Stanton, Alice, Starr, John M, Stefansdottir, Lilja, Straker, Leon, Sulem, Patrick, Sveinbjornsson, Gardar, Swertz, Morris A, Taylor, Adele M, Taylor, Kent D, Terzikhan, Natalie, Tham, Yih-Chung, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tillander, Annika, Tracy, Russell P, Tusié-Luna, Teresa, Tzoulaki, Ioanna, Vaccargiu, Simona, Vangipurapu, Jagadish, Veldink, Jan H, Vitart, Veronique, Völker, Uwe, Vuoksimaa, Eero, Wakil, Salma M, Waldenberger, Melanie, Wander, Gurpreet S, Wang, Ya Xing, Wareham, Nicholas J, Wild, Sarah, Yajnik, Chittaranjan S, Yuan, Jian-Min, Zeng, Lingyao, Zhang, Liang, Zhou, Jie, Amin, Najaf, Asselbergs, Folkert W, Bakker, Stephan J L, Becker, Diane M, Lehne, Benjamin, Bennett, David A, Van Den Berg, Leonard H, Berndt, Sonja I, Bharadwaj, Dwaipayan, Bielak, Lawrence F, Bochud, Murielle, Boehnke, Mike, Bouchard, Claude, Bradfield, Jonathan P, Brody, Jennifer A, Campbell, Archie, Carmi, Shai, Caulfield, Mark J, Cesarini, David, Chambers, John C, Chandak, Giriraj Ratan, Cheng, Ching-Yu, Ciullo, Marina, Cornelis, Marilyn, Cusi, Daniele, Smith, George Davey, Deary, Ian J, Dorajoo, Rajkumar, Van Duijn, Cornelia M, Ellinghaus, David, Erdmann, Jeanette, Eriksson, Johan G, Evangelou, Evangelos, Evans, Michele K, Faul, Jessica D, Feenstra, Bjarke, Feitosa, Mary, Foisy, Sylvain, Franke, Andre, Friedlander, Yechiel, Gasparini, Paolo, Gieger, Christian, Gonzalez, Clicerio, Goyette, Philippe, Grant, Struan F A, Griffiths, Lyn R, Groop, Leif, Gudnason, Vilmundur, Gyllensten, Ulf, Hakonarson, Hakon, Hamsten, Anders, Van Der Harst, Pim, Heng, Chew-Kiat, Hicks, Andrew A, Hochner, Hagit, Huikuri, Heikki, Hunt, Steven C, Jaddoe, Vincent W V, De Jager, Philip L, Johannesson, Magnus, Johansson, Åsa, Jonas, Jost B, Jukema, J Wouter, Junttila, Juhani, Kaprio, Jaakko, Kardia, Sharon L. R., Karpe, Fredrik, Kumari, Meena, Laakso, Markku, Van Der Laan, Sander W, Lahti, Jari, Laudes, Matthias, Lea, Rodney A, Lieb, Wolfgang, Lumley, Thomas, Martin, Nicholas G, März, Winfried, Matullo, Giuseppe, McCarthy, Mark I, Medland, Sarah E, Merriman, Tony R, Metspalu, Andres, Meyer, Brian F, Mohlke, Karen L, Montgomery, Grant W, Mook-Kanamori, Dennis, Munroe, Patricia B, North, Kari E, Nyholt, Dale R, O’connell, Jeffery R, Ober, Carole, Oldehinkel, Albertine J, Palmas, Walter, Palmer, Colin, Pasterkamp, Gerard G, Patin, Etienne, Pennell, Craig E, Perusse, Louis, Peyser, Patricia A, Pirastu, Mario, Polderman, Tinca J. C., Porteous, David J, Posthuma, Danielle, Psaty, Bruce M, Rioux, John D, Rivadeneira, Fernando, Rotimi, Charles, Rotter, Jerome I, Rudan, Igor, Den Ruijter, Hester M, Sanghera, Dharambir K, Sattar, Naveed, Schmidt, Reinhold, Schulze, Matthias B, Schunkert, Heribert, Scott, Robert A, Shuldiner, Alan R, Sim, Xueling, Small, Neil, Smith, Jennifer A, Sotoodehnia, Nona, Tai, E-Shyong, Teumer, Alexander, Timpson, Nicholas J, Toniolo, Daniela, Tregouet, David-Alexandre, Tuomi, Tiinamaija, Vollenweider, Peter, Wang, Carol A, Weir, David R, Whitfield, John B, Wijmenga, Cisca, Wong, Tien-Yin, Wright, John, Yang, Jingyun, Yu, Lei, Zemel, Babette S, Zonderman, Alan B, Perola, Markus, Magnusson, Patrik K. E., Uitterlinden, André G, Kooner, Jaspal S, Chasman, Daniel I, Loos, Ruth J. F., Franceschini, Nora, Franke, Lude, Haley, Chris S, Hayward, Caroline, Walters, Robin G, Perry, John R. B., Esko, Tōnu, Helgason, Agnar, Stefansson, Kari, Joshi, Peter K, Kubo, Michiaki, and Wilson, James F
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631/208/1397 ,631/208/730 ,article ,631/208/205 ,631/208/721 ,3. Good health - Abstract
In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
127. Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals
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Lee, James J, Wedow, Robbee, Okbay, Aysu, Kong, Edward, Maghzian, Omeed, Zacher, Meghan, Nguyen-Viet, Tuan Anh, Bowers, Peter, Sidorenko, Julia, Karlsson Linnér, Richard, Fontana, Mark Alan, Kundu, Tushar, Lee, Chanwook, Li, Hui, Li, Ruoxi, Royer, Rebecca, Timshel, Pascal N, Walters, Raymond K, Willoughby, Emily A, Yengo, Loïc, 23andMe Research Team, COGENT (Cognitive Genomics Consortium), Social Science Genetic Association Consortium, Alver, Maris, Bao, Yanchun, Clark, David W, Day, Felix R, Furlotte, Nicholas A, Joshi, Peter K, Kemper, Kathryn E, Kleinman, Aaron, Langenberg, Claudia, Mägi, Reedik, Trampush, Joey W, Verma, Shefali Setia, Wu, Yang, Lam, Max, Zhao, Jing Hua, Zheng, Zhili, Boardman, Jason D, Campbell, Harry, Freese, Jeremy, Harris, Kathleen Mullan, Hayward, Caroline, Herd, Pamela, Kumari, Meena, Lencz, Todd, Luan, Jian'an, Malhotra, Anil K, Metspalu, Andres, Milani, Lili, Ong, Ken K, Perry, John RB, Porteous, David J, Ritchie, Marylyn D, Smart, Melissa C, Smith, Blair H, Tung, Joyce Y, Wareham, Nicholas J, Wilson, James F, Beauchamp, Jonathan P, Conley, Dalton C, Esko, Tõnu, Lehrer, Steven F, Magnusson, Patrik KE, Oskarsson, Sven, Pers, Tune H, Robinson, Matthew R, Thom, Kevin, Watson, Chelsea, Chabris, Christopher F, Meyer, Michelle N, Laibson, David I, Yang, Jian, Johannesson, Magnus, Koellinger, Philipp D, Turley, Patrick, Visscher, Peter M, Benjamin, Daniel J, and Cesarini, David
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Adult ,Aged, 80 and over ,Male ,Multifactorial Inheritance ,Middle Aged ,Polymorphism, Single Nucleotide ,3. Good health ,Cohort Studies ,Phenotype ,Educational Status ,Humans ,Female ,Aged ,Genome-Wide Association Study - Abstract
Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1 million individuals and identify 1,271 independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10 independent genome-wide-significant SNPs and estimate a SNP heritability of around 0.3% in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11-13% of the variance in educational attainment and 7-10% of the variance in cognitive performance. This prediction accuracy substantially increases the utility of polygenic scores as tools in research., Medical Research Council (MC_UU_12015/1), Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0512-10135), MRC (MC_PC_13048), Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0617-10149)
128. Selected hydrologic data for northern Utah Valley, Utah, 1935-82
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Appel, Cynthia L., primary, Clark, David W., additional, and Fairbanks, Paul E., additional
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- 1982
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129. Effects of growth medium on phage production and induction in Escherichia coli K-12 lambda lysogens
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Clark, David W., primary, Meyer, Hans-Peter, additional, Leist, Christian, additional, and Fiechter, Armin, additional
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- 1986
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130. Physics transparencies
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Clark, David W., primary
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- 1979
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131. Emigration of the peamouth chub, Mylocheilus caurinus, across a dilute seawater bridge: an experimental zoogeographic study
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Clark, David W., primary and McInerney, John E., additional
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- 1974
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132. EFFECT OF CAPTOPRIL ON BLOOD PRESSURE AND VASCULAR RESISTANCE IN NORMOTENSIVE AND GENETICALLY HYPERTENSIVE RATS
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Phelan, E. Linton, primary and Clark, David W. J., additional
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- 1979
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133. Selected hydrologic data from wells in the East Shore area of the Great Salt Lake, Utah, 1985
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Plantz, Gerald G., primary, Appel, Cynthia L., additional, Clark, David W., additional, Lambert, Patrick M., additional, and Puryear, Robert L., additional
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- 1985
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134. Experimental study of air bubbles in a simulated cardiopulmonary bypass system with flow constriction
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Tanasawa, I., primary, Wotton, D.R., additional, Yang, Wen-Jei, additional, and Clark, David W., additional
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- 1970
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135. LETTER RULING ALLOWS REDUCED SECTION 121 EXCLUSION FOR FAMILY GROWTH.
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CLARK, DAVID W. and PULLIAM, DARLENE
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- 2017
136. Implementing Single-Use Technology in Tangential Flow Filtration Systems in Clinical Manufacturing.
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Keqiang Shen, Be Van Vu, Nikunj Dani, Fluke, Bryan, Lei Xue, and Clark, David W.
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ULTRAFILTRATION ,INDUSTRIAL productivity ,BIOTECHNOLOGICAL process control ,MANUFACTURING processes ,FILTERS & filtration - Abstract
The article presents a study that evaluates the performance, control of operation, productivity, and overall cost savings of single-use (SU) technology in tangential flow filtration (TFF) systems in clinical manufacturing. It states that SU TFF was implemented in cGMP clinical manufacturing facility. It indicates that the operation of the single-use system is easier than the stainless steel ultrafiltration-diafiltration systems and the performance is comparable.
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- 2010
137. IRS may not assess a deficiency 9 years after a failed tax-free merger for predecessor company's failure to file.
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Clark, David W. and Pulliam, Darlene
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TAX free reorganization ,MERGERS & acquisitions ,TAX courts ,CONSOLIDATED corporate tax returns - Abstract
The article focuses on the filing of tax free merger of Capital Fire Insurance company into New Capital Fire Inc at Tax Court. It includes information on the filing of U.S. Corporation Income Tax Return by New Capital. It also includes information on the barring of Internal Revenue Services from assessing the company's predecessor corporations.
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- 2017
138. Tax Court allows discount for assumption of estate taxes.
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Clark, David W. and Pulliam, Darlene
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INHERITANCE & transfer tax ,TAXATION of estate planning ,MARKET value ,TAX courts - Abstract
The article focuses on the decision of the Tax Court on the tax discount for the assumption of estate taxes in the U.S. It offers overview of the case involving 89-year-old widow Jean Steinberg, who entered into an agreement with her adult daughters to gift cash and securities to them in exchange to pay any federal or state estate tax liabilities. The court allows the discount assuming the gift's fair market value (FMV) as determined under willing buyer/seller analysis.
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- 2016
139. A SURVEY OF RECENT ACCOUNTS OF THE MOUNTAIN LION (PUMA CONCOLOR) IN ARKANSAS
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Clark, David W., White, Steffany C., Bowers, Annalea K., Lucio, Leah D., and Heidt, Gary A.
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- 2002
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140. EFFECT OF CAPTOPRIL ON BLOOD PRESSURE AND VASCULAR RESISTANCE IN NORMOTENSIVE AND GENETICALLY HYPERTENSIVE RATS
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Phelan, E. Linton and Clark, David W. J.
- Abstract
The effect of Captopril on blood pressure and hind‐limb vascular resistance was studied in normotensive (N) and genetically hypertensive (GH) rats of the New Zealand strain who were anaesthetized with chloralose (75 mg/kg, intravenously). The hind limbs were perfused at a constant rate of 1 mL/min with the rat's own blood, and a five‐minute delay coil was incorporated into the circuit. Captopril (10 μg/kg to 1000 μg/kg), given either intravenously (in the jugular vein) or intra‐arterially (into the femoral artery of the perfused limb), lowered the blood pressure and the limb vascular resistance in a dose‐dependent manner. When Captopril was given intravenously, the delay in the pump circuit allowed the responses of the systemic blood pressure and the responses of the hind‐limb perfusion pressure to be separated by about five minutes. A fall in perfusion pressure occurred only when Captopril entered the limb; it was not abolished by surgical denervation of the limb and had no reflex neurogenic component. When Captopril was given intra‐arterially (200 μg/kg) into the limb there was an immediate drop in resistance followed five minutes later by a second fall in resistance when the circulating drug reentered the limb. This locally mediated response was not diminished by prior nephrectomy or concurrent infusion of saralasin, although both of these procedures abolished the blood pressure response. The local limb response is possibly due to potentiation of bradykinin‐induced vasodilatation. Responses of GH and N rats were similar, and there was no evidence that a captopril‐sensitive mechanism involving either the renin‐angiotensin or the kallikrein‐ bradykinin systems plays any part in maintaining genetic hypertension.
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- 1977
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141. TAX COURT ALLOWS DISCOUNT OF GIFT VALUE FOR ASSUMPTION OF ESTATE TAXES.
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Clark, David W. and Pulliam, Darlene
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GIFT taxes ,TAXATION ,FAIR value - Abstract
The article discusses a U.S. Tax Court ruling concerning the fair market valuation (FMV) of gifts. Jean Steinberg made gifts of cash and securities to her four daughters. On her gift tax return she lowered the FMV of those gifts by an amount equal to her daughters' future potential tax liability. The Internal Revenue Service challenged that maneuver. The Tax Court, to a degree, upheld Steinberg.
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- 2014
142. Why do I teach?
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Clark, David W.
- Subjects
- *
HIGH school teachers , *HIGH school students ,UNITED States history education - Abstract
The article describes why the author likes teaching American history at B. Reed Henderson High School in Pennsylvania. The author says that the passion of studying history, which he shares with students, is a reward in itself and that is why he teaches the subject. According to the author, he was diagnosed with cancer on a holiday weekend but forgot about the disease after the school hours and was filled with energy and excitement.
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- 2009
143. LETTERS.
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Wernsman, Scott, Rule, Debbie, Risley, Mike, Lucas, Justin, Chandler, Mike, Beer, Tom, Costa, Michael, Kohn, Mitch, Clark, David W., Pizzillo, Jack, Temple, Robert, and Gussel, Bud
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LETTERS to the editor - Abstract
Presents letters to the editor in response to articles published in the July 18, 2005 edition of "Sports Illustrated." Reader response to the summer issue; Response to the article "Sports Tribes," on communities of amateur athletes in the United States; Response to the column "Where Are They Now?" on Jim Plunkett; Others.
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- 2005
144. Sibutramine may be associated with memory impairment.
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J, Clark David W and Mira, Harrison-Woolrych
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- 2004
145. The genetic landscape of Scotland and the Isles.
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Gilbert, Edmund, O'Reilly, Seamus, Merrigan, Michael, McGettigan, Darren, Vitart, Veronique, Joshi, Peter K., Clark, David W., Campbell, Harry, Hayward, Caroline, Ring, Susan M., Golding, Jean, Goodfellow, Stephanie, Navarro, Pau, Kerr, Shona M., Amador, Carmen, Campbell, Archie, Haley, Chris S., Porteous, David J., Cavalleri, Gianpiero L., and Wilson, James F.
- Subjects
- *
ISLANDS , *FOSSIL DNA , *MIDDLE Ages - Abstract
Britain and Ireland are known to show population genetic structure; however, large swathes of Scotland, in particular, have yet to be described. Delineating the structure and ancestry of these populations will allow variant discovery efforts to focus efficiently on areas not represented in existing cohorts. Thus, we assembled genotype data for 2,554 individuals from across the entire archipelago with geographically restricted ancestry, and performed population structure analyses and comparisons to ancient DNA. Extensive geographic structuring is revealed, from broad scales such as a NE to SW divide in mainland Scotland, through to the finest scale observed to date: across 3 km in the Northern Isles. Many genetic boundaries are consistent with Dark Age kingdoms of Gaels, Picts, Britons, and Norse. Populations in the Hebrides, the Highlands, Argyll, Donegal, and the Isle of Man show characteristics of isolation. We document a pole of Norwegian ancestry in the north of the archipelago (reaching 23 to 28% in Shetland) which complements previously described poles of Germanic ancestry in the east, and "Celtic" to the west. This modern genetic structure suggests a northwestern British or Irish source population for the ancient Gaels that contributed to the founding of Iceland. As rarer variants, often with larger effect sizes, become the focus of complex trait genetics, more diverse rural cohorts may be required to optimize discoveries in British and Irish populations and their considerable global diaspora. [ABSTRACT FROM AUTHOR]
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- 2019
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146. Associations of autozygosity with a broad range of human phenotypes
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Dennis O. Mook-Kanamori, Salma M. Wakil, Lisa R. Yanek, Dominique P.V. de Kleijn, Gert J. de Borst, Alison D. Murray, Kamran Guity, Vincent W. V. Jaddoe, Mario Pirastu, Carole Ober, Giuseppe Matullo, Charles N. Rotimi, Daniela Ruggiero, Teresa Tusié-Luna, Wolfgang Lieb, Chew-Kiat Heng, John R. B. Perry, Hortensia Moreno-Macías, Jie Zhou, John M. Starr, Juhani Junttila, Lei Yu, Danielle Posthuma, Marcus Dörr, Yingchang Lu, Jonathan P. Bradfield, Einat Granot-Hershkovitz, Karina Meidtner, Wouter van Rheenen, T Esko, Maris Alver, Wen-Jane Lee, Zhengming Chen, Jennifer A. Brody, Paolo Gasparini, Yii-Der Ida Chen, Cinzia Sala, Peter P. Pramstaller, Gauri Prasad, Nana Matoba, Natalie Terzikhan, Simonetta Guarrera, Bjarke Feenstra, Peter Vollenweider, Smeeta Shrestha, Yi-Jen Hung, Lilja Stefansdottir, David R. Weir, Felix R. Day, Antonietta Robino, Liang Zhang, Lluis Quintana-Murci, Nicholas J. Timpson, Robyn E Wootton, Xue W. Mei, Dharambir K. Sanghera, Gisli Masson, Debbie A Lawlor, Thomas Meitinger, Sharon L.R. Kardia, Peter K. Joshi, Frank J. A. van Rooij, Claude Bouchard, Cassandra N. Spracklen, Ken K. Ong, Taulant Muka, Guanjie Chen, Laura J. Scott, Walter Palmas, Daniel I. Chasman, Sarah E. Medland, Krista Fischer, Blair H. Smith, Jon K. Sigurdsson, Leon Straker, Clara Viberti, Yuan Shi, Louis Pérusse, Peter J. van der Most, Timo Tõnis Sikka, Chris Haley, Kuang Lin, Leif Groop, Hester M. den Ruijter, Hakon Hakonarson, Masato Akiyama, Stephan J. L. Bakker, Sonja I. Berndt, Jeffery R. O'Connell, Cisca Wijmenga, Daniele Cusi, Lorena Orozco, Kristjan H. S. Moore, Kevin Sandow, Stephen S. Rich, Stephanie J. Loomis, George Davey Smith, Cornelia M. van Duijn, Sharvari Rahul Shukla, Agnar Helgason, Thorsten Kessler, Anuj Goel, Dan Mason, David W. Clark, James S. Pankow, Simona Vaccargiu, Uwe Völker, Tamara B. Harris, Matthew A. Allison, Clicerio Gonzalez, Sarju Ralhan, I-Te Lee, Matthias Laudes, Yen-Feng Chiu, Neil Poulter, Benjamin Lehne, John Wright, Lawrence F. Bielak, Philip L. De Jager, Reinhold Schmidt, Ya Xing Wang, Matthias Nauck, Diana L. Cousminer, Patrick Deelen, Ani Manichaikul, Stephen J. Chanock, Anders Hamsten, Barry I. Freedman, Gudmar Thorleifsson, Peter Kraft, Ozren Polasek, Jie Yao, Yoshinori Murakami, Paul M. Ridker, Anubha Mahajan, Struan F.A. Grant, Claudia Schurmann, Bjarni Gunnarsson, Catriona L. K. Barnes, Jessica van Setten, Sandosh Padmanabhan, Alena Stančáková, Markus M. Lerch, Anuradha Jagadeesan, Franco Giulianini, Daniel F. Gudbjartsson, Dwaipayan Bharadwaj, Shengchao Alfred Li, Peter S. Sever, Trevor A. Mori, Albertine J. Oldehinkel, Koichi Matsuda, Xueling Sim, Evangelos Evangelou, André G. Uitterlinden, Pekka Jousilahti, Yukihide Momozawa, Ioanna Tzoulaki, Chao A. Hsiung, Ginevra Biino, Murielle Bochud, Hannele Mattsson, Ilja M. Nolte, Sarah H. Wild, Patricia B. Munroe, Jianjun Liu, Bruce M. Psaty, Giriraj R. Chandak, Masahiro Kanai, Tony R. Merriman, Teemu Palviainen, Rodney A. Lea, Janie Corley, Nicholas J. Wareham, Alan B. Zonderman, Makoto Hirata, Matthew J. Bixley, Caroline Hayward, Nora Franceschini, Kristel R van Eijk, Etienne Patin, Daniel Shriner, Niek Verweij, Xiuqing Guo, Fredrik Karpe, Ruth J. F. Loos, Tiinamaija Tuomi, Ashley van der Spek, Patricia A. Peyser, Jessica D. Faul, Christian Fuchsberger, David Cesarini, Alex S. F. Doney, Janine F. Felix, Cornelius A. Rietveld, Jagadish Vangipurapu, Tanguy Corre, Line Skotte, Rajkumar Dorajoo, Catherine Igartua, Meena Kumari, Nona Sotoodehnia, Leonard H. van den Berg, Najaf Amin, Dale R. Nyholt, Harry Campbell, Massimiliano Cocca, Scott D. Gordon, Patrik K. E. Magnusson, John C. Chambers, Traci M. Bartz, Mike A. Nalls, Tin Aung, Nduna Dzimiri, Colin N. A. Palmer, Rob M. van Dam, Johanna Kuusisto, Russell P. Tracy, Anna Damulina, Pierre-Emmanuel Morange, Sylvain Foisy, Jing Hua Zhao, Nicholas G. Martin, Ching-Yu Cheng, Mariaelisa Graff, Rashmi B. Prasad, Alice Stanton, David-Alexandre Trégouët, Yu Guo, Helen R. Warren, Lyn R. Griffiths, Weihua Meng, Annika Tillander, Christa Meisinger, Albert V. Smith, Mark I. McCarthy, Jingyun Yang, Marine Germain, Neil Small, Linda Broer, Vilmundur Gudnason, Gunnar K. Pálsson, Michele K. Evans, Alexander Teumer, Mark J. Caulfield, Giorgia Girotto, Thomas Lumley, Tinca J. C. Polderman, Wei Zhao, Carlos A. Aguilar-Salinas, Jari Lahti, Matthew L. Albert, Yechiel Friedlander, Veikko Salomaa, Iona Y Millwood, Jan H. Veldink, Archie Campbell, Andres Metspalu, Ulf Gyllensten, Grant W. Montgomery, Veronique Vitart, Jai Rup Singh, Saima Afaq, Alan R. Shuldiner, Miao-Li Chee, Adebowale Adeyemo, Jennifer A. Smith, David A. van Heel, Jaspal S. Kooner, Daniela Toniolo, Cristian Pattaro, Jerome I. Rotter, John Whitfield, Melissa C. Smart, Kari E. North, Salman M. Tajuddin, Tallapragada Divya Sri Priyanka, Christopher A. Haiman, Diane M. Becker, Bernhard K. Krämer, Paul Elliott, Lihua Wang, He Gao, Patrick Sulem, Jinyan Huang, Chiea Chuen Khor, Ruifang Li-Gao, Åsa Johansson, Winfried März, Shai Carmi, Ilaria Gandin, Eric Boerwinkle, Gardar Sveinbjornsson, Saskia P. Hagenaars, Sander W. van der Laan, Gerard Pasterkamp, E-Shyong Tai, Hagit Hochner, Yih Chung Tham, Kent D. Taylor, Kari Stefansson, Matt J. Neville, Craig E. Pennell, Yanchun Bao, Annelot M. Dekker, Helena Schmidt, Mehdi Hedayati, Joshua Elliott, Ian J. Deary, Iris E. Jansen, Judith B. Borja, Edith Hofer, Martin Gögele, Igor Rudan, Lude Franke, Matthias Munz, Folkert W. Asselbergs, Bengt Sennblad, Imo Hofer, John D. Rioux, Pim van der Harst, Bahareh Sedaghati-khayat, Giovanni Cugliari, Morris A. Swertz, Francine Grodstein, Erwin P. Bottinger, Carol A. Wang, Andre Franke, Brian F. Meyer, Adele M. Taylor, Klodian Dhana, Jian'an Luan, Constance Turman, Robert A. Scott, May E. Montasser, Alison Pattie, Marco Brumat, Liming Li, Heiner Boeing, Karen L. Mohlke, Clemens Baumbach, Bishwa Raj Sapkota, Unnur Thorsteinsdottir, Naveed Sattar, Amy R. Bentley, Matthias B. Schulze, Ivana Kolcic, Stella Trompet, Sarah E. Harris, Ayo P. Doumatey, Charumathi Sabanayagam, David Eccles, Mary F. Feitosa, Jost B. Jonas, Massimo Mezzavilla, Mark O. Goodarzi, David Ellinghaus, Heribert Schunkert, Christian Gieger, Heikki V. Huikuri, Lingyao Zeng, Johan G. Eriksson, Woon-Puay Koh, Yucheng Jia, Gurpreet Singh Wander, James F. Wilson, Torgny Karlsson, Steven C. Hunt, Weihua Zhang, Maria Pina Concas, Zoltán Kutalik, Rebecca Rohde, Chittaranjan S. Yajnik, Yasaman Saba, Dabeeru C. Rao, Robin G. Walters, Reedik Mägi, Marie Loh, Eero Vuoksimaa, Josyf C. Mychaleckyj, Katri Räikkönen, Philippe Goyette, M. Arfan Ikram, Alicia Huerta-Chagoya, David J. Porteous, Teresa Nutile, J. Wouter Jukema, Noha A. Yousri, Yoichiro Kamatani, Maryam S. Daneshpour, Babette S. Zemel, Rona J. Strawbridge, Tien Yin Wong, Claudia Langenberg, Amy Moore, Marcus E. Kleber, Fereidoun Azizi, Avner Halevy, Erika Salvi, Francis S. Collins, Markku Laakso, Tim Kacprowski, S. Sunna Ebenesersdóttir, William R. Scott, Michael Boehnke, Jin-Fang Chai, Markus Perola, Nicola Pirastu, Wayne Huey-Herng Sheu, Robert Karlsson, Lenore J. Launer, Lili Milani, Renée de Mutsert, Fernando Rivadeneira, David A. Bennett, Nicola D. Kerrison, Paolo Manunta, Graciela E. Delgado, Magnus Johannesson, Carolina Medina-Gomez, Alanna C. Morrison, Kay-Tee Khaw, Jian-Min Yuan, Jaakko Kaprio, Melanie Waldenberger, Ralf Ewert, Hugoline G. de Haan, Andrew A. Hicks, Yukinori Okada, Maria Sabater-Lleal, Marilyn C. Cornelis, Stephanie J. London, Federica Rizzi, Jeanette Erdmann, Marina Ciullo, Michiaki Kubo, University of Edinburgh, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Osaka University Graduate School of Medicine, Laboratory for Cardiovascular Genomics and Informatics [Yokohama] (RIKEN IMS), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN)-RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), deCODE genetics [Reykjavik], Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK (BIHR), Area Science Park, Università degli studi di Trieste = University of Trieste, MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Harbor UCLA Medical Center [Torrance, Ca.], Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, Department of Electrical and Computer Engineering [Waterloo] (ECE), University of Waterloo [Waterloo], Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Institute of Pop. Genetics, CNR, Sassari, Shardna life science Pula Cagliari, Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL), Medstar Research Institute, Florida State University [Tallahassee] (FSU), University Medical Center [Utrecht], Centre for Population Health Sciences, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), California State University [Sacramento], Department of Thrombosis and Haemostasis, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Medical University Graz, Department of Neurology, Alzheimer Centre, VU Medical Centre, Amsterdam, Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, Heidelberg, Frederick National Laboratory for Cancer Research (FNLCR), Wellcome Trust Centre of Human Genetics, University of Oxford, Department of Epidemiology, German Institute of Human Nutrition, University Medical Center Groningen [Groningen] (UMCG), Institute of Genetics and Biophysics, National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), Department of Medicine, Surgery, and Dentistry, University of Milano, Icelandic Heart Association, Kopavogur, Iceland., Department of Epidemiology [Rotterdam], Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Glasgow, Department of Cardiology, Leiden University Medical Center, Leiden, Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, Queen Mary University of London (QMUL), General Internal Medicine, Johns Hopkins School of Medicine, Johns Hopkins University School of Medicine [Baltimore], Institut de biologie moléculaire des plantes (IBMP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris] (IP), Genentech, Inc., Genentech, Inc. [San Francisco], University of Tartu, Duke-NUS Medical School [Singapore], Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DifE), Leibniz Association, Human Genome Sequencing Center, Baylor College of Medicine, Baylor College of Medicine (BCM), Baylor University-Baylor University, University of San Carlos, Office of Population Studies Foundation, Icahn School of Medicine at Mount Sinai [New York] (MSSM), King‘s College London, Division of Cancer Epidemiology and Genetics, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), University of Oxford, Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, Division of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, Department of Internal Medicine B, University Medicine Greifswald, Greifswald, University of Chicago, University of Huddersfield, Infectious diseases division, Department of internal medicine, Washington University in Saint Louis (WUSTL), Section on Nephrology [Winston-Salem, NC, USA] (Department of Internal Medicine), Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center-Wake Forest Baptist Medical Center, Radcliffe Department of Medicine [Oxford], Harvard School of Public Health, Kunming University of Science and Technology (KMUST), Sans affiliation, University of Southern California (USC), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), MRC Centrer for Nutritional Epidemiology and Cancer Prevention and Survival, University of Cambridge [UK] (CAM), National University of Singapore (NUS), Experimental Cardiology Laboratory (ECL), Unirversity Medical Center, Department of Medical Statistics, Epidemiology and Medical Informatics, University of Zagreb, Department of Medical Genetics, Department of Medicine, University of Eastern Finland-Kuopio University Hospital, MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, Capital Normal University [Beijing], Saw Swee Hock School of Public Health, National Institute for Environmental Health Sciences Research Triangle Park, Brown University, MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, Toyota Research Institute, Helmholtz Zentrum München = German Research Center for Environmental Health, Department of Chemistry and Biochemistry [Boulder], University of Colorado [Boulder], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital de la Timone [CHU - APHM] (TIMONE), Metacohorts Consortium, Universiteit Leiden, Institute of Clinical Chemistry and Laboratory Medicine, University of Groningen [Groningen], Medical Research Concil Epidemiology Unit, Institute of Medical Science, Faculty of Medicine, Genetics and Pathology, Imperial College London, Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Brigham and Women's Hospital [Boston], Erasmus University Rotterdam, Department of Chronic Disease Prevention, National Institute for Health and Welfare [Helsinki], Department of Biostatistics and Center for Statistical Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Stockholm Bioinformatics Center (SBC), Stockholm University, Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, University of Utrecht, Utrecht, INRH, Department of Genetics, Los Angeles Biomedical Research Institute (LA BioMed), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], Western General Hospital, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Medical Research Council, Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute-University of Pittsburgh Graduate School of Public Health, Zhengzhou University of Light Industry, Department of Electrical and Electronic Engineering [Niigata Univ.], Niigata University, Genetic Epidemiology Unit, University College of London [London] (UCL), Aston Business School, Aston University [Birmingham], Division of Cancer Epidemiology and Genetics [Bethesda, MD, États-Unis], Centre Hospitalier Universitaire Vaudois (CHUV), Pennington Biomedical Research Center, University of Washington [Seattle], Guy's and St Thomas' Hospitals, Northwestern Polytechnical University [Xi'an] (NPU), Department of Social Medicine, University of Bristol [Bristol], Department of Genomics of Common Disease [London, UK], Imperial College London-Hammersmith Hospital NHS Imperial College Healthcare, Department of Internal Medicine, Institute of Clinical Molecular Biology, Kiel University, Medizinische Klinik II, Universität zu Lübeck = University of Lübeck [Lübeck], Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina, Institute for Social Research, University of Michigan System-University of Michigan System, Division of Statistical Genomics, Washington University School of Medicine, Institute for Clinical Molecular Biology, Christian-Albrechts-Universität zu Kiel (CAU), Department of Physics, RISSC-Lab-University of Naples Federico II = Università degli studi di Napoli Federico II, Lund University [Lund], Icelandic Heart Association, Heart Preventive Clinic and Research Institute, The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Génétique moléculaire de la neurotransmission et des processus neurodégénératifs (LGMNPN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Medical Research Center Oulu, University of Oulu, University of Utah School of Medicine [Salt Lake City], The Generation R Study, Pediatrics, Epidemiology, Center for Translational and Computational Neuroimmunology [New York, NY, États-Unis] (CTCN), Department of Neurology [New York, NY, États-Unis], Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York]-Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York], Universität Heidelberg [Heidelberg] = Heidelberg University, Interuniversity Cardiology Institute Netherlands, School of Public Health, University of Michigan [Dearborn], Department of Epidemiology and Public Health, University of Kuopio, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Institute of Epidemiology and Biobank PopGen, Department of Biostatistics, University of Washington, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Clinical Institute of Medical and Chemical Laboratory Diagnostics, Karl-Franzens-Universität Graz, Department of Genetics, Biology and Biochemistry, Università degli studi di Torino = University of Turin (UNITO), Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), QIMR Berghofer Medical Research Institute, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC)-UNC Gillings School of Global Public Health-Carolina Center for Genome Sciences, University of Illinois [Chicago] (UIC), University of Illinois System, Experimental Cardiology Laboratory, Genetic Epidemiology and Clinical Research Group, Umea University Hospital, Functional Genomics, Erasmus Medical Centre, National Human Genome Research Institute (NHGRI), School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Department of Pathological Biochemistry, Royal Infirmary, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Institute of Metabolic Science, MRC, University of Maryland School of Medicine [Baltimore, MD, USA], Centre for Molecular Epidemiology, Centre for Causal Analyses in Translational Epidemiology, University of Bristol [Bristol]-Medical Research Council, IRCCS San Raffaele Scientific Institute [Milan, Italie], U937, Génomique cardiovasculaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), University of Michigan System, HMNC Brain Health, Singapore Eye Research Institute, Partenaires INRAE, Institut d'Électronique et des Technologies du numéRique (IETR), Université de Nantes (UN)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Department of Psychiatry and Psychotherapy, Rheinische Friedrich-Wilhelms-Universität Bonn, University of Groningen, Department of Genomics of Common Disease, Department of Microbiology, The Freeman Hospital, Department Biostatistics University of North Carolina, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Clark, D. W., Okada, Y., Moore, K. H. S., Mason, D., Pirastu, N., Gandin, I., Mattsson, H., Barnes, C. L. K., Lin, K., Zhao, J. H., Deelen, P., Rohde, R., Schurmann, C., Guo, X., Giulianini, F., Zhang, W., Medina-Gomez, C., Karlsson, R., Bao, Y., Bartz, T. M., Baumbach, C., Biino, G., Bixley, M. J., Brumat, M., Chai, J. -F., Corre, T., Cousminer, D. L., Dekker, A. M., Eccles, D. A., van Eijk, K. R., Fuchsberger, C., Gao, H., Germain, M., Gordon, S. D., de Haan, H. G., Harris, S. E., Hofer, E., Huerta-Chagoya, A., Igartua, C., Jansen, I. E., Jia, Y., Kacprowski, T., Karlsson, T., Kleber, M. E., Li, S. A., Li-Gao, R., Mahajan, A., Matsuda, K., Meidtner, K., Meng, W., Montasser, M. E., van der Most, P. J., Munz, M., Nutile, T., Palviainen, T., Prasad, G., Prasad, R. B., Priyanka, T. D. S., Rizzi, F., Salvi, E., Sapkota, B. R., Shriner, D., Skotte, L., Smart, M. C., Smith, A. V., van der Spek, A., Spracklen, C. N., Strawbridge, R. J., Tajuddin, S. M., Trompet, S., Turman, C., Verweij, N., Viberti, C., Wang, L., Warren, H. R., Wootton, R. E., Yanek, L. R., Yao, J., Yousri, N. A., Zhao, W., Adeyemo, A. A., Afaq, S., Aguilar-Salinas, C. A., Akiyama, M., Albert, M. L., Allison, M. A., Alver, M., Aung, T., Azizi, F., Bentley, A. R., Boeing, H., Boerwinkle, E., Borja, J. B., de Borst, G. J., Bottinger, E. P., Broer, L., Campbell, H., Chanock, S., Chee, M. -L., Chen, G., Chen, Y. -D. I., Chen, Z., Chiu, Y. -F., Cocca, M., Collins, F. S., Concas, M. P., Corley, J., Cugliari, G., van Dam, R. M., Damulina, A., Daneshpour, M. S., Day, F. R., Delgado, G. E., Dhana, K., Doney, A. S. F., Dorr, M., Doumatey, A. P., Dzimiri, N., Ebenesersdottir, S. S., Elliott, J., Elliott, P., Ewert, R., Felix, J. F., Fischer, K., Freedman, B. I., Girotto, G., Goel, A., Gogele, M., Goodarzi, M. O., Graff, M., Granot-Hershkovitz, E., Grodstein, F., Guarrera, S., Gudbjartsson, D. F., Guity, K., Gunnarsson, B., Guo, Y., Hagenaars, S. P., Haiman, C. A., Halevy, A., Harris, T. B., Hedayati, M., van Heel, D. A., Hirata, M., Hofer, I., Hsiung, C. A., Huang, J., Hung, Y. -J., Ikram, M. A., Jagadeesan, A., Jousilahti, P., Kamatani, Y., Kanai, M., Kerrison, N. D., Kessler, T., Khaw, K. -T., Khor, C. C., de Kleijn, D. P. V., Koh, W. -P., Kolcic, I., Kraft, P., Kramer, B. K., Kutalik, Z., Kuusisto, J., Langenberg, C., Launer, L. J., Lawlor, D. A., Lee, I. -T., Lee, W. -J., Lerch, M. M., Li, L., Liu, J., Loh, M., London, S. J., Loomis, S., Lu, Y., Luan, J., Magi, R., Manichaikul, A. W., Manunta, P., Masson, G., Matoba, N., Mei, X. W., Meisinger, C., Meitinger, T., Mezzavilla, M., Milani, L., Millwood, I. Y., Momozawa, Y., Moore, A., Morange, P. -E., Moreno-Macias, H., Mori, T. A., Morrison, A. C., Muka, T., Murakami, Y., Murray, A. D., de Mutsert, R., Mychaleckyj, J. C., Nalls, M. A., Nauck, M., Neville, M. J., Nolte, I. M., Ong, K. K., Orozco, L., Padmanabhan, S., Palsson, G., Pankow, J. S., Pattaro, C., Pattie, A., Polasek, O., Poulter, N., Pramstaller, P. P., Quintana-Murci, L., Raikkonen, K., Ralhan, S., Rao, D. C., van Rheenen, W., Rich, S. S., Ridker, P. M., Rietveld, C. A., Robino, A., van Rooij, F. J. A., Ruggiero, D., Saba, Y., Sabanayagam, C., Sabater-Lleal, M., Sala, C. F., Salomaa, V., Sandow, K., Schmidt, H., Scott, L. J., Scott, W. R., Sedaghati-Khayat, B., Sennblad, B., van Setten, J., Sever, P. J., Sheu, W. H. -H., Shi, Y., Shrestha, S., Shukla, S. R., Sigurdsson, J. K., Sikka, T. T., Singh, J. R., Smith, B. H., Stancakova, A., Stanton, A., Starr, J. M., Stefansdottir, L., Straker, L., Sulem, P., Sveinbjornsson, G., Swertz, M. A., Taylor, A. M., Taylor, K. D., Terzikhan, N., Tham, Y. -C., Thorleifsson, G., Thorsteinsdottir, U., Tillander, A., Tracy, R. P., Tusie-Luna, T., Tzoulaki, I., Vaccargiu, S., Vangipurapu, J., Veldink, J. H., Vitart, V., Volker, U., Vuoksimaa, E., Wakil, S. M., Waldenberger, M., Wander, G. S., Wang, Y. X., Wareham, N. J., Wild, S., Yajnik, C. S., Yuan, J. -M., Zeng, L., Zhang, L., Zhou, J., Amin, N., Asselbergs, F. W., Bakker, S. J. L., Becker, D. M., Lehne, B., Bennett, D. A., van den Berg, L. H., Berndt, S. I., Bharadwaj, D., Bielak, L. F., Bochud, M., Boehnke, M., Bouchard, C., Bradfield, J. P., Brody, J. A., Campbell, A., Carmi, S., Caulfield, M. J., Cesarini, D., Chambers, J. C., Chandak, G. R., Cheng, C. -Y., Ciullo, M., Cornelis, M., Cusi, D., Smith, G. D., Deary, I. J., Dorajoo, R., van Duijn, C. M., Ellinghaus, D., Erdmann, J., Eriksson, J. G., Evangelou, E., Evans, M. K., Faul, J. D., Feenstra, B., Feitosa, M., Foisy, S., Franke, A., Friedlander, Y., Gasparini, P., Gieger, C., Gonzalez, C., Goyette, P., Grant, S. F. A., Griffiths, L. R., Groop, L., Gudnason, V., Gyllensten, U., Hakonarson, H., Hamsten, A., van der Harst, P., Heng, C. -K., Hicks, A. A., Hochner, H., Huikuri, H., Hunt, S. C., Jaddoe, V. W. V., De Jager, P. L., Johannesson, M., Johansson, A., Jonas, J. B., Jukema, J. W., Junttila, J., Kaprio, J., Kardia, S. L. R., Karpe, F., Kumari, M., Laakso, M., van der Laan, S. W., Lahti, J., Laudes, M., Lea, R. A., Lieb, W., Lumley, T., Martin, N. G., Marz, W., Matullo, G., Mccarthy, M. I., Medland, S. E., Merriman, T. R., Metspalu, A., Meyer, B. F., Mohlke, K. L., Montgomery, G. W., Mook-Kanamori, D., Munroe, P. B., North, K. E., Nyholt, D. R., O'Connell, J. R., Ober, C., Oldehinkel, A. J., Palmas, W., Palmer, C., Pasterkamp, G. G., Patin, E., Pennell, C. E., Perusse, L., Peyser, P. A., Pirastu, M., Polderman, T. J. C., Porteous, D. J., Posthuma, D., Psaty, B. M., Rioux, J. D., Rivadeneira, F., Rotimi, C., Rotter, J. I., Rudan, I., Den Ruijter, H. M., Sanghera, D. K., Sattar, N., Schmidt, R., Schulze, M. B., Schunkert, H., Scott, R. A., Shuldiner, A. R., Sim, X., Small, N., Smith, J. A., Sotoodehnia, N., Tai, E. -S., Teumer, A., Timpson, N. J., Toniolo, D., Tregouet, D. -A., Tuomi, T., Vollenweider, P., Wang, C. A., Weir, D. R., Whitfield, J. 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[0000-0002-8532-5087], Franke, Lude [0000-0002-5159-8802], Haley, Chris S [0000-0002-9811-0210], Hayward, Caroline [0000-0002-9405-9550], Walters, Robin G [0000-0002-9179-0321], Joshi, Peter K [0000-0002-6361-5059], Wilson, James F [0000-0001-5751-9178], Apollo - University of Cambridge Repository, Moore, Kristjan HS [0000-0002-9579-4362], Luan, Jian'an [0000-0003-3137-6337], Grant, Struan FA [0000-0003-2025-5302], Jaddoe, Vincent WV [0000-0003-2939-0041], Polderman, Tinca JC [0000-0001-5564-301X], Magnusson, Patrik KE [0000-0002-7315-7899], Loos, Ruth JF [0000-0002-8532-5087], Neurology, Human genetics, Amsterdam Reproduction & Development (AR&D), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Stem Cell Aging Leukemia and Lymphoma (SALL), Institute for Molecular Medicine Finland, Department of Psychology and Logopedics, University Management, Developmental Psychology Research Group, Staff Services, Cognitive and Brain Aging, Research Programs Unit, Diabetes and Obesity Research Program, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Clinicum, University of Helsinki, Centre of Excellence in Complex Disease Genetics, Department of Public Health, Genetic Epidemiology, Helsinki Collegium for Advanced Studies, HUS Abdominal Center, Endokrinologian yksikkö, Bradford Teaching Hospitals NHS Foundation Trust [Bradford, UK] (BTHFT), University of Trieste, Université de Lausanne (UNIL), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Consiglio Nazionale delle Ricerche (CNR), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut Pasteur [Paris], University of Oxford [Oxford], Medical Genetics, Dept. RSD and Public Health, IRCCS-Burlo Garofolo/University of Trieste, sans affiliation, Helmholtz-Zentrum München (HZM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institute of Cardiovascular Science, University College London, Hammersmith Hospital NHS Imperial College Healthcare-Imperial College London, Universität zu Lübeck [Lübeck], University of Ioannina Medical School, Università degli studi di Napoli Federico II-RISSC-Lab, Universität Heidelberg [Heidelberg], University of Turin, University of California-University of California, Nantes Université (NU)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), University of Helsinki-University of Helsinki, Université de Nantes (UN)-Université de Rennes 1 (UR1), Erasmus MC other, Internal Medicine, and Applied Economics
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0301 basic medicine ,631/208/1397 ,Chemistry(all) ,Health Status ,[SDV]Life Sciences [q-bio] ,LOCI ,General Physics and Astronomy ,MESH: Haplotype ,MESH: Cognition ,030105 genetics & heredity ,Runs of Homozygosity ,Biochemistry ,Consanguinity ,Cognition ,Inbreeding depression ,2.1 Biological and endogenous factors ,Body Size ,Inbreeding ,Skyldleikarækt ,Aetiology ,Human phenotypes ,lcsh:Science ,MESH: Health Status ,Genetics ,Multidisciplinary ,Inbreeding Depression ,Confounding ,Homozygote ,RUNS ,631/208/205 ,631/208/721 ,3. Good health ,genomic inbreeding coefficients ,MESH: Risk-Taking ,631/208/730 ,Autozygosit ,homozygosity ,Erfðarannsóknir ,Medical Genetics ,genomic inbreeding coefficient ,MESH: Homozygote ,Offspring ,Science ,Autozygosity ,Blóðsifjar ,610 Medicine & health ,Biology ,INBREEDING DEPRESSION ,HOMOZYGOSITY ,FERTILITY ,QUANTIFICATION ,Physics and Astronomy(all) ,General Biochemistry, Genetics and Molecular Biology ,Article ,Association ,03 medical and health sciences ,Risk-Taking ,360 Social problems & social services ,Journal Article ,Humans ,ddc:610 ,Allele ,Alleles ,Medicinsk genetik ,Genetic association study ,MESH: Consanguinity ,MESH: Body Size ,MESH: Humans ,Biochemistry, Genetics and Molecular Biology(all) ,MESH: Alleles ,Haplotype ,MESH: Fertility ,General Chemistry ,Brain Disorders ,MESH: Inbreeding Depression ,030104 developmental biology ,Fertility ,Haplotypes ,Genetic markers ,lcsh:Q ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,3111 Biomedicine ,Genetics and Molecular Biology(all) - Abstract
Publisher's version (útgefin grein)., In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding., This paper is the work of the ROHgen consortium. We thank the Sigma T2D Consortium, whose members are detailed in Supplementary Note 3. We thank the UK Biobank Resource, approved under application 19655; we acknowledge funding from the UK Medical Research Council Human Genetics Unit and MRC Doctoral Training Programme in Precision Medicine. We also thank Neil Robertson, Wellcome Trust Centre for Human Genetics, Oxford, for use of his author details management software, Authorial. Finally, we thank all the participants, researchers and funders of ROHgen cohorts. Cohort-specific acknowledgements are in Supplementary Data 2; personal acknowledgements and disclosures are in Supplementary Note 2. We thank Rachel Edwards for administrative assistance.
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- 2019
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147. Variation in the SERPINA6/SERPINA1 locus alters morning plasma cortisol, hepatic corticosteroid binding globulin expression, gene expression in peripheral tissues, and risk of cardiovascular disease.
- Author
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Crawford AA, Bankier S, Altmaier E, Barnes CLK, Clark DW, Ermel R, Friedrich N, van der Harst P, Joshi PK, Karhunen V, Lahti J, Mahajan A, Mangino M, Nethander M, Neumann A, Pietzner M, Sukhavasi K, Wang CA, Bakker SJL, Bjorkegren JLM, Campbell H, Eriksson J, Gieger C, Hayward C, Jarvelin MR, McLachlan S, Morris AP, Ohlsson C, Pennell CE, Price J, Rudan I, Ruusalepp A, Spector T, Tiemeier H, Völzke H, Wilson JF, Michoel T, Timpson NJ, Smith GD, and Walker BR
- Subjects
- Adrenal Cortex Hormones blood, Adult, Biological Specimen Banks, Cardiovascular Diseases blood, Cardiovascular Diseases epidemiology, Cardiovascular Diseases pathology, Female, Gene Expression Regulation, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Liver metabolism, Liver pathology, Male, Mendelian Randomization Analysis, Middle Aged, Myocardial Infarction blood, Myocardial Infarction pathology, Polymorphism, Single Nucleotide genetics, Quantitative Trait Loci genetics, United Kingdom, Cardiovascular Diseases genetics, Myocardial Infarction genetics, Transcortin genetics, alpha 1-Antitrypsin genetics
- Abstract
The stress hormone cortisol modulates fuel metabolism, cardiovascular homoeostasis, mood, inflammation and cognition. The CORtisol NETwork (CORNET) consortium previously identified a single locus associated with morning plasma cortisol. Identifying additional genetic variants that explain more of the variance in cortisol could provide new insights into cortisol biology and provide statistical power to test the causative role of cortisol in common diseases. The CORNET consortium extended its genome-wide association meta-analysis for morning plasma cortisol from 12,597 to 25,314 subjects and from ~2.2 M to ~7 M SNPs, in 17 population-based cohorts of European ancestries. We confirmed the genetic association with SERPINA6/SERPINA1. This locus contains genes encoding corticosteroid binding globulin (CBG) and α1-antitrypsin. Expression quantitative trait loci (eQTL) analyses undertaken in the STARNET cohort of 600 individuals showed that specific genetic variants within the SERPINA6/SERPINA1 locus influence expression of SERPINA6 rather than SERPINA1 in the liver. Moreover, trans-eQTL analysis demonstrated effects on adipose tissue gene expression, suggesting that variations in CBG levels have an effect on delivery of cortisol to peripheral tissues. Two-sample Mendelian randomisation analyses provided evidence that each genetically-determined standard deviation (SD) increase in morning plasma cortisol was associated with increased odds of chronic ischaemic heart disease (0.32, 95% CI 0.06-0.59) and myocardial infarction (0.21, 95% CI 0.00-0.43) in UK Biobank and similarly in CARDIoGRAMplusC4D. These findings reveal a causative pathway for CBG in determining cortisol action in peripheral tissues and thereby contributing to the aetiology of cardiovascular disease.
- Published
- 2021
- Full Text
- View/download PDF
148. Autozygosity influences cardiometabolic disease-associated traits in the AWI-Gen sub-Saharan African study.
- Author
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Ceballos FC, Hazelhurst S, Clark DW, Agongo G, Asiki G, Boua PR, Xavier Gómez-Olivé F, Mashinya F, Norris S, Wilson JF, and Ramsay M
- Subjects
- Africa South of the Sahara epidemiology, Cardiovascular Diseases epidemiology, Female, Genes, Recessive, Genome-Wide Association Study, Homozygote, Humans, Inbreeding Depression, Male, Obesity epidemiology, Obesity genetics, Phenotype, Sex Factors, Urbanization, Cardiovascular Diseases genetics, Consanguinity, Genome, Human
- Abstract
The analysis of the effects of autozygosity, measured as the change of the mean value of a trait among offspring of genetic relatives, reveals the existence of directional dominance or overdominance. In this study we detect evidence of the effect of autozygosity in 4 out of 13 cardiometabolic disease-associated traits using data from more than 10,000 sub-Saharan African individuals recruited from Ghana, Burkina Faso, Kenya and South Africa. The effect of autozygosity on these phenotypes is found to be sex-related, with inbreeding having a significant decreasing effect in men but a significant increasing effect in women for several traits (body mass index, subcutaneous adipose tissue, low-density lipoproteins and total cholesterol levels). Overall, the effect of inbreeding depression is more intense in men. Differential effects of inbreeding depression are also observed between study sites with different night-light intensity used as proxy for urban development. These results suggest a directional dominant genetic component mediated by environmental interactions and sex-specific differences in genetic architecture for these traits in the Africa Wits-INDEPTH partnership for Genomic Studies (AWI-Gen) cohort.
- Published
- 2020
- Full Text
- View/download PDF
149. The multifunctional protein PACS-1 is required for HDAC2- and HDAC3-dependent chromatin maturation and genomic stability.
- Author
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Mani C, Tripathi K, Luan S, Clark DW, Andrews JF, Vindigni A, Thomas G, and Palle K
- Subjects
- Cell Cycle, Cell Line, Tumor, Cell Nucleus metabolism, Cytosol metabolism, DNA Replication, Gene Knockdown Techniques, HeLa Cells, Humans, Proteasome Endopeptidase Complex metabolism, Protein Stability, Vesicular Transport Proteins genetics, Chromatin physiology, Genomic Instability, Histone Deacetylase 1 metabolism, Histone Deacetylases metabolism, Vesicular Transport Proteins physiology
- Abstract
Phosphofurin acidic cluster sorting protein-1 (PACS-1) is a multifunctional membrane traffic regulator that plays important roles in organ homeostasis and disease. In this study, we elucidate a novel nuclear function for PACS-1 in maintaining chromosomal integrity. PACS-1 progressively accumulates in the nucleus during cell cycle progression, where it interacts with class I histone deacetylases 2 and 3 (HDAC2 and HDAC3) to regulate chromatin dynamics by maintaining the acetylation status of histones. PACS-1 knockdown results in the proteasome-mediated degradation of HDAC2 and HDAC3, compromised chromatin maturation, as indicated by elevated levels of histones H3K9 and H4K16 acetylation, and, consequently, increased replication stress-induced DNA damage and genomic instability.
- Published
- 2020
- Full Text
- View/download PDF
150. Associations of autozygosity with a broad range of human phenotypes.
- Author
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Clark DW, Okada Y, Moore KHS, Mason D, Pirastu N, Gandin I, Mattsson H, Barnes CLK, Lin K, Zhao JH, Deelen P, Rohde R, Schurmann C, Guo X, Giulianini F, Zhang W, Medina-Gomez C, Karlsson R, Bao Y, Bartz TM, Baumbach C, Biino G, Bixley MJ, Brumat M, Chai JF, Corre T, Cousminer DL, Dekker AM, Eccles DA, van Eijk KR, Fuchsberger C, Gao H, Germain M, Gordon SD, de Haan HG, Harris SE, Hofer E, Huerta-Chagoya A, Igartua C, Jansen IE, Jia Y, Kacprowski T, Karlsson T, Kleber ME, Li SA, Li-Gao R, Mahajan A, Matsuda K, Meidtner K, Meng W, Montasser ME, van der Most PJ, Munz M, Nutile T, Palviainen T, Prasad G, Prasad RB, Priyanka TDS, Rizzi F, Salvi E, Sapkota BR, Shriner D, Skotte L, Smart MC, Smith AV, van der Spek A, Spracklen CN, Strawbridge RJ, Tajuddin SM, Trompet S, Turman C, Verweij N, Viberti C, Wang L, Warren HR, Wootton RE, Yanek LR, Yao J, Yousri NA, Zhao W, Adeyemo AA, Afaq S, Aguilar-Salinas CA, Akiyama M, Albert ML, Allison MA, Alver M, Aung T, Azizi F, Bentley AR, Boeing H, Boerwinkle E, Borja JB, de Borst GJ, Bottinger EP, Broer L, Campbell H, Chanock S, Chee ML, Chen G, Chen YI, Chen Z, Chiu YF, Cocca M, Collins FS, Concas MP, Corley J, Cugliari G, van Dam RM, Damulina A, Daneshpour MS, Day FR, Delgado GE, Dhana K, Doney ASF, Dörr M, Doumatey AP, Dzimiri N, Ebenesersdóttir SS, Elliott J, Elliott P, Ewert R, Felix JF, Fischer K, Freedman BI, Girotto G, Goel A, Gögele M, Goodarzi MO, Graff M, Granot-Hershkovitz E, Grodstein F, Guarrera S, Gudbjartsson DF, Guity K, Gunnarsson B, Guo Y, Hagenaars SP, Haiman CA, Halevy A, Harris TB, Hedayati M, van Heel DA, Hirata M, Höfer I, Hsiung CA, Huang J, Hung YJ, Ikram MA, Jagadeesan A, Jousilahti P, Kamatani Y, Kanai M, Kerrison ND, Kessler T, Khaw KT, Khor CC, de Kleijn DPV, Koh WP, Kolcic I, Kraft P, Krämer BK, Kutalik Z, Kuusisto J, Langenberg C, Launer LJ, Lawlor DA, Lee IT, Lee WJ, Lerch MM, Li L, Liu J, Loh M, London SJ, Loomis S, Lu Y, Luan J, Mägi R, Manichaikul AW, Manunta P, Másson G, Matoba N, Mei XW, Meisinger C, Meitinger T, Mezzavilla M, Milani L, Millwood IY, Momozawa Y, Moore A, Morange PE, Moreno-Macías H, Mori TA, Morrison AC, Muka T, Murakami Y, Murray AD, de Mutsert R, Mychaleckyj JC, Nalls MA, Nauck M, Neville MJ, Nolte IM, Ong KK, Orozco L, Padmanabhan S, Pálsson G, Pankow JS, Pattaro C, Pattie A, Polasek O, Poulter N, Pramstaller PP, Quintana-Murci L, Räikkönen K, Ralhan S, Rao DC, van Rheenen W, Rich SS, Ridker PM, Rietveld CA, Robino A, van Rooij FJA, Ruggiero D, Saba Y, Sabanayagam C, Sabater-Lleal M, Sala CF, Salomaa V, Sandow K, Schmidt H, Scott LJ, Scott WR, Sedaghati-Khayat B, Sennblad B, van Setten J, Sever PJ, Sheu WH, Shi Y, Shrestha S, Shukla SR, Sigurdsson JK, Sikka TT, Singh JR, Smith BH, Stančáková A, Stanton A, Starr JM, Stefansdottir L, Straker L, Sulem P, Sveinbjornsson G, Swertz MA, Taylor AM, Taylor KD, Terzikhan N, Tham YC, Thorleifsson G, Thorsteinsdottir U, Tillander A, Tracy RP, Tusié-Luna T, Tzoulaki I, Vaccargiu S, Vangipurapu J, Veldink JH, Vitart V, Völker U, Vuoksimaa E, Wakil SM, Waldenberger M, Wander GS, Wang YX, Wareham NJ, Wild S, Yajnik CS, Yuan JM, Zeng L, Zhang L, Zhou J, Amin N, Asselbergs FW, Bakker SJL, Becker DM, Lehne B, Bennett DA, van den Berg LH, Berndt SI, Bharadwaj D, Bielak LF, Bochud M, Boehnke M, Bouchard C, Bradfield JP, Brody JA, Campbell A, Carmi S, Caulfield MJ, Cesarini D, Chambers JC, Chandak GR, Cheng CY, Ciullo M, Cornelis M, Cusi D, Smith GD, Deary IJ, Dorajoo R, van Duijn CM, Ellinghaus D, Erdmann J, Eriksson JG, Evangelou E, Evans MK, Faul JD, Feenstra B, Feitosa M, Foisy S, Franke A, Friedlander Y, Gasparini P, Gieger C, Gonzalez C, Goyette P, Grant SFA, Griffiths LR, Groop L, Gudnason V, Gyllensten U, Hakonarson H, Hamsten A, van der Harst P, Heng CK, Hicks AA, Hochner H, Huikuri H, Hunt SC, Jaddoe VWV, De Jager PL, Johannesson M, Johansson Å, Jonas JB, Jukema JW, Junttila J, Kaprio J, Kardia SLR, Karpe F, Kumari M, Laakso M, van der Laan SW, Lahti J, Laudes M, Lea RA, Lieb W, Lumley T, Martin NG, März W, Matullo G, McCarthy MI, Medland SE, Merriman TR, Metspalu A, Meyer BF, Mohlke KL, Montgomery GW, Mook-Kanamori D, Munroe PB, North KE, Nyholt DR, O'connell JR, Ober C, Oldehinkel AJ, Palmas W, Palmer C, Pasterkamp GG, Patin E, Pennell CE, Perusse L, Peyser PA, Pirastu M, Polderman TJC, Porteous DJ, Posthuma D, Psaty BM, Rioux JD, Rivadeneira F, Rotimi C, Rotter JI, Rudan I, Den Ruijter HM, Sanghera DK, Sattar N, Schmidt R, Schulze MB, Schunkert H, Scott RA, Shuldiner AR, Sim X, Small N, Smith JA, Sotoodehnia N, Tai ES, Teumer A, Timpson NJ, Toniolo D, Tregouet DA, Tuomi T, Vollenweider P, Wang CA, Weir DR, Whitfield JB, Wijmenga C, Wong TY, Wright J, Yang J, Yu L, Zemel BS, Zonderman AB, Perola M, Magnusson PKE, Uitterlinden AG, Kooner JS, Chasman DI, Loos RJF, Franceschini N, Franke L, Haley CS, Hayward C, Walters RG, Perry JRB, Esko T, Helgason A, Stefansson K, Joshi PK, Kubo M, and Wilson JF
- Subjects
- Alleles, Haplotypes, Homozygote, Humans, Body Size genetics, Cognition, Consanguinity, Fertility genetics, Health Status, Inbreeding Depression genetics, Risk-Taking
- Abstract
In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F
ROH ) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.- Published
- 2019
- Full Text
- View/download PDF
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