Author: "Mari Nelis" / Language: undetermined - Searchworks@Jio Institute Digital Library Search Results

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25 results on '"Mari Nelis"'

1. SARS-CoV-2 dual infection with Delta and Omicron variants in an immunocompetent host: a case report

Author: Aare Abroi, Ulvi Gerst Talas, Merit Pauskar, Arina Shablinskaja, Tuuli Reisberg, Heiki Niglas, Taavi Päll, Mari Nelis, Ingrid Tagen, Pilleriin Soodla, Irja Lutsar, and Kristi Huik
Subjects: Microbiology (medical), Infectious Diseases, General Medicine
Published: 2022

2. FinnGen: Unique genetic insights from combining isolated population and national health register data

Author: Mitja I. Kurki, Juha Karjalainen, Priit Palta, Timo P. Sipilä, Kati Kristiansson, Kati Donner, Mary P. Reeve, Hannele Laivuori, Mervi Aavikko, Mari A. Kaunisto, Anu Loukola, Elisa Lahtela, Hannele Mattsson, Päivi Laiho, Pietro Della Briotta Parolo, Arto Lehisto, Masahiro Kanai, Nina Mars, Joel Rämö, Tuomo Kiiskinen, Henrike O. Heyne, Kumar Veerapen, Sina Rüeger, Susanna Lemmelä, Wei Zhou, Sanni Ruotsalainen, Kalle Pärn, Tero Hiekkalinna, Sami Koskelainen, Teemu Paajanen, Vincent Llorens, Javier Gracia-Tabuenca, Harri Siirtola, Kadri Reis, Abdelrahman G. Elnahas, Katriina Aalto-Setälä, Kaur Alasoo, Mikko Arvas, Kirsi Auro, Shameek Biswas, Argyro Bizaki-Vallaskangas, Olli Carpen, Chia-Yen Chen, Oluwaseun A. Dada, Zhihao Ding, Margaret G. Ehm, Kari Eklund, Martti Färkkilä, Hilary Finucane, Andrea Ganna, Awaisa Ghazal, Robert R. Graham, Eric Green, Antti Hakanen, Marco Hautalahti, Åsa Hedman, Mikko Hiltunen, Reetta Hinttala, Iiris Hovatta, Xinli Hu, Adriana Huertas-Vazquez, Laura Huilaja, Julie Hunkapiller, Howard Jacob, Jan-Nygaard Jensen, Heikki Joensuu, Sally John, Valtteri Julkunen, Marc Jung, Juhani Junttila, Kai Kaarniranta, Mika Kähönen, Risto M. Kajanne, Lila Kallio, Reetta Kälviäinen, Jaakko Kaprio, Nurlan Kerimov, Johannes Kettunen, Elina Kilpeläinen, Terhi Kilpi, Katherine Klinger, Veli-Matti Kosma, Teijo Kuopio, Venla Kurra, Triin Laisk, Jari Laukkanen, Nathan Lawless, Aoxing Liu, Simonne Longerich, Reedik Mägi, Johanna Mäkelä, Antti Mäkitie, Anders Malarstig, Arto Mannermaa, Joseph Maranville, Athena Matakidou, Tuomo Meretoja, Sahar V. Mozaffari, Mari EK. Niemi, Marianna Niemi, Teemu Niiranen, Christopher J. O’Donnell, Ma’en Obeidat, George Okafo, Hanna M. Ollila, Antti Palomäki, Tuula Palotie, Jukka Partanen, Dirk S. Paul, Margit Pelkonen, Rion K. Pendergrass, Slavé Petrovski, Anne Pitkäranta, Adam Platt, David Pulford, Eero Punkka, Pirkko Pussinen, Neha Raghavan, Fedik Rahimov, Deepak Rajpal, Nicole A. Renaud, Bridget Riley-Gillis, Rodosthenis Rodosthenous, Elmo Saarentaus, Aino Salminen, Eveliina Salminen, Veikko Salomaa, Johanna Schleutker, Raisa Serpi, Huei-yi Shen, Richard Siegel, Kaisa Silander, Sanna Siltanen, Sirpa Soini, Hilkka Soininen, Jae H. Sul, Ioanna Tachmazidou, Kaisa Tasanen, Pentti Tienari, Sanna Toppila-Salmi, Taru Tukiainen, Tiinamaija Tuomi, Joni A. Turunen, Jacob C. Ulirsch, Felix Vaura, Petri Virolainen, Jeffrey Waring, Dawn Waterworth, Robert Yang, Mari Nelis, Anu Reigo, Andres Metspalu, Lili Milani, Tõnu Esko, Caroline Fox, Aki S. Havulinna, Markus Perola, Samuli Ripatti, Anu Jalanko, Tarja Laitinen, Tomi Mäkelä, Robert Plenge, Mark McCarthy, Heiko Runz, Mark J. Daly, and Aarno Palotie
Abstract: Population isolates such as Finland provide benefits in genetic studies because the allelic spectrum of damaging alleles in any gene is often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%), which survived the founding bottleneck, as opposed to being distributed over a much larger number of ultra--rare variants. While this advantage is well-- established in Mendelian genetics, its value in common disease genetics has been less explored. FinnGen aims to study the genome and national health register data of 500,000 Finns, already reaching 224,737 genotyped and phenotyped participants. Given the relatively high median age of participants (63 years) and dominance of hospital-based recruitment, FinnGen is enriched for many disease endpoints often underrepresented in population-based studies (e.g., rarer immune-mediated diseases and late onset degenerative and ophthalmologic endpoints). We report here a genome-wide association study (GWAS) of 1,932 clinical endpoints defined from nationwide health registries. We identify genome--wide significant associations at 2,491 independent loci. Among these, finemapping implicates 148 putatively causal coding variants associated with 202 endpoints, 104 with low allele frequency (AFWe studied a benchmark set of 15 diseases that had previously been investigated in large genome-wide association studies. FinnGen discovery analyses were meta-analysed in Estonian and UK biobanks. We identify 30 novel associations, primarily low-frequency variants strongly enriched, in or specific to, the Finnish population and Uralic language family neighbors in Estonia and Russia.These findings demonstrate the power of bottlenecked populations to find unique entry points into the biology of common diseases through low-frequency, high impact variants. Such high impact variants have a potential to contribute to medical translation including drug discovery.
Published: 2022

3. Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss

Author: Natalia Trpchevska, Maxim B. Freidin, Linda Broer, Berthe C. Oosterloo, Shuyang Yao, Yitian Zhou, Barbara Vona, Charles Bishop, Argyro Bizaki-Vallaskangas, Barbara Canlon, Fabio Castellana, Daniel I. Chasman, Stacey Cherny, Kaare Christensen, Maria Pina Concas, Adolfo Correa, Ran Elkon, Jonas Mengel-From, Yan Gao, Anne B.S. Giersch, Giorgia Girotto, Alexander Gudjonsson, Vilmundur Gudnason, Nancy L. Heard-Costa, Ronna Hertzano, Jacob v.B. Hjelmborg, Jens Hjerling-Leffler, Howard J. Hoffman, Jaakko Kaprio, Johannes Kettunen, Kristi Krebs, Anna K. Kähler, Francois Lallemend, Lenore J. Launer, I-Min Lee, Hampton Leonard, Chuan-Ming Li, Hubert Lowenheim, Patrik K.E. Magnusson, Joyce van Meurs, Lili Milani, Cynthia C. Morton, Antti Mäkitie, Mike A. Nalls, Giuseppe Giovanni Nardone, Marianne Nygaard, Teemu Palviainen, Sheila Pratt, Nicola Quaranta, Joel Rämö, Elmo Saarentaus, Rodolfo Sardone, Claudia L. Satizabal, John M. Schweinfurth, Sudha Seshadri, Eric Shiroma, Eldad Shulman, Eleanor Simonsick, Christopher Spankovich, Anke Tropitzsch, Volker M. Lauschke, Patrick F. Sullivan, Andre Goedegebure, Christopher R. Cederroth, Frances M.K. Williams, Andries Paul Nagtegaal, Andres Metspalu, Mari Nelis, Reedik Mägi, Tõnu Esko, Tampere University, Clinical Medicine, Department of Otology and Oral Diseases, Institute for Molecular Medicine Finland, HUS Head and Neck Center, Clinicum, Korva-, nenä- ja kurkkutautien klinikka, Genetic Epidemiology, Genomics of Neurological and Neuropsychiatric Disorders, Complex Disease Genetics, Trpchevska, Natalia, Freidin, Maxim B, Broer, Linda, Oosterloo, Berthe C, Yao, Shuyang, Zhou, Yitian, Vona, Barbara, Bishop, Charle, Bizaki-Vallaskangas, Argyro, Canlon, Barbara, Castellana, Fabio, Chasman, Daniel I, Cherny, Stacey, Christensen, Kaare, Concas, Maria Pina, Correa, Adolfo, Elkon, Ran, Mengel-From, Jona, Gao, Yan, Giersch, Anne B S, Girotto, Giorgia, Gudjonsson, Alexander, Gudnason, Vilmundur, Heard-Costa, Nancy L, Hertzano, Ronna, Hjelmborg, Jacob V B, Hjerling-Leffler, Jen, Hoffman, Howard J, Kaprio, Jaakko, Kettunen, Johanne, Krebs, Kristi, Kähler, Anna K, Lallemend, Francoi, Launer, Lenore J, Lee, I-Min, Leonard, Hampton, Li, Chuan-Ming, Lowenheim, Hubert, Magnusson, Patrik K E, van Meurs, Joyce, Milani, Lili, Morton, Cynthia C, Mäkitie, Antti, Nalls, Mike A, Nardone, Giuseppe Giovanni, Nygaard, Marianne, Palviainen, Teemu, Pratt, Sheila, Quaranta, Nicola, Rämö, Joel, Saarentaus, Elmo, Sardone, Rodolfo, Satizabal, Claudia L, Schweinfurth, John M, Seshadri, Sudha, Shiroma, Eric, Shulman, Eldad, Simonsick, Eleanor, Spankovich, Christopher, Tropitzsch, Anke, Lauschke, Volker M, Sullivan, Patrick F, Goedegebure, Andre, Cederroth, Christopher R, Williams, Frances M K, Nagtegaal, Andries Paul, Internal Medicine, and Otorhinolaryngology and Head and Neck Surgery
Subjects: basal cells, hair cells, cochlea, spindle cell, ARHL, GWAS, genetics, hearing loss, root cells, spindle cells, stria vascularis, Animals, Cochlea, Genome-Wide Association Study, Humans, Mice, Stria Vascularis, Deafness, Hearing Loss, basal cell, hair cell, Hair-cells, Heritability, otorhinolaryngologic diseases, Genetics, Pathogenicity, Gwas data, Deafne, Ld score regression, Ganglion neurons, Genetics (clinical), Animal, 1184 Genetics, developmental biology, physiology, hearing lo, Stria Vasculari, Inner, 3142 Public health care science, environmental and occupational health, root cell, Differentiation, Degeneration, 3111 Biomedicine, genetic, Noise, Human
Abstract: Hearing loss is one of the top contributors to years lived with disability and is a risk factor for dementia. Molecular evidence on the cellular origins of hearing loss in humans is growing. Here, we performed a genome-wide association meta-analysis of clinically diagnosed and self-reported hearing impairment on 723,266 individuals and identified 48 significant loci, 10 of which are novel. A large proportion of associations comprised missense variants, half of which lie within known familial hearing loss loci. We used single-cell RNA-sequencing data from mouse cochlea and brain and mapped common-variant genomic results to spindle, root, and basal cells from the stria vascularis, a structure in the cochlea necessary for normal hearing. Our findings indicate the importance of the stria vascularis in the mechanism of hearing impairment, providing future paths for developing targets for therapeutic intervention in hearing loss. publishedVersion
Published: 2022

4. The individual and global impact of copy-number variants on complex human traits

Author: Chiara Auwerx, Maarja Lepamets, Marie C. Sadler, Marion Patxot, Miloš Stojanov, David Baud, Reedik Mägi, Eleonora Porcu, Alexandre Reymond, Zoltán Kutalik, Tõnu Esko, Andres Metspalu, Lili Milani, and Mari Nelis
Subjects: Multifactorial Inheritance, Phenotype, DNA Copy Number Variations, Liver-Specific Organic Anion Transporter 1, Genetics, Humans, Female, Polymorphism, Single Nucleotide, Genetics (clinical), Genome-Wide Association Study
Abstract: The impact of copy-number variations (CNVs) on complex human traits remains understudied. We called CNVs in 331,522 UK Biobank participants and performed genome-wide association studies (GWASs) between the copy number of CNV-proxy probes and 57 continuous traits, revealing 131 signals spanning 47 phenotypes. Our analysis recapitulated well-known associations (e.g., 1q21 and height), revealed the pleiotropy of recurrent CNVs (e.g., 26 and 16 traits for 16p11.2-BP4-BP5 and 22q11.21, respectively), and suggested gene functionalities (e.g., MARF1 in female reproduction). Forty-eight CNV signals (38%) overlapped with single-nucleotide polymorphism (SNP)-GWASs signals for the same trait. For instance, deletion of PDZK1, which encodes a urate transporter scaffold protein, decreased serum urate levels, while deletion of RHD, which encodes the Rhesus blood group D antigen, associated with hematological traits. Other signals overlapped Mendelian disorder regions, suggesting variable expressivity and broad impact of these loci, as illustrated by signals mapping to Rotor syndrome (SLCO1B1/3), renal cysts and diabetes syndrome (HNF1B), or Charcot-Marie-Tooth (PMP22) loci. Total CNV burden negatively impacted 35 traits, leading to increased adiposity, liver/kidney damage, and decreased intelligence and physical capacity. Thirty traits remained burden associated after correcting for CNV-GWAS signals, pointing to a polygenic CNV architecture. The burden negatively correlated with socio-economic indicators, parental lifespan, and age (survivorship proxy), suggesting a contribution to decreased longevity. Together, our results showcase how studying CNVs can expand biological insights, emphasizing the critical role of this mutational class in shaping human traits and arguing in favor of a continuum between Mendelian and complex diseases.
Published: 2021

5. Assessment of the genetic and clinical determinants of hip fracture risk: Genome-wide association and Mendelian randomization study

Author: Maria Nethander, Eivind Coward, Ene Reimann, Louise Grahnemo, Maiken E. Gabrielsen, Carl Wibom, Reedik Mägi, Thomas Funck-Brentano, Mari Hoff, Arnulf Langhammer, Ulrika Pettersson-Kymmer, Kristian Hveem, Claes Ohlsson, Mari Nelis, Lili Milani, Tõnu Esko, and Andres Metspalu
Subjects: Male, genome-wide association study, Hip Fractures, Femur Neck, Orthopaedics, Mendelian Randomization Analysis, General Biochemistry, Genetics and Molecular Biology, hip fracture, Bone Density, Ortopedi, mendelian randomization, Humans, Female, bone mineral density, Genome-Wide Association Study
Abstract: Hip fracture is the clinically most important fracture, but the genetic architecture of hip fracture is unclear. Here, we perform a large-scale hip fracture genome-wide association study meta-analysis and Mendelian randomization study using five cohorts from European biobanks. The results show that five genetic signals associate with hip fractures. Among these, one signal associates with falls, but not with bone mineral density (BMD), while four signals are in loci known to be involved in bone biology. Mendelian randomization analyses demonstrate a strong causal effect of decreased femoral neck BMD and moderate causal effects of Alzheimer’s disease and having ever smoked regularly on risk of hip fractures. The substantial causal effect of decreased femoral neck BMD on hip fractures in both young and old subjects and in both men and women supports the use of change in femoral neck BMD as a surrogate outcome for hip fractures in clinical trials.
Published: 2022

6. A cross-disorder dosage sensitivity map of the human genome

Author: Ryan L. Collins, Joseph T. Glessner, Eleonora Porcu, Maarja Lepamets, Rhonda Brandon, Christopher Lauricella, Lide Han, Theodore Morley, Lisa-Marie Niestroj, Jacob Ulirsch, Selin Everett, Daniel P. Howrigan, Philip M. Boone, Jack Fu, Konrad J. Karczewski, Georgios Kellaris, Chelsea Lowther, Diane Lucente, Kiana Mohajeri, Margit Nõukas, Xander Nuttle, Kaitlin E. Samocha, Mi Trinh, Farid Ullah, Urmo Võsa, Matthew E. Hurles, Swaroop Aradhya, Erica E. Davis, Hilary Finucane, James F. Gusella, Aura Janze, Nicholas Katsanis, Ludmila Matyakhina, Benjamin M. Neale, David Sanders, Stephanie Warren, Jennelle C. Hodge, Dennis Lal, Douglas M. Ruderfer, Jeanne Meck, Reedik Mägi, Tõnu Esko, Alexandre Reymond, Zoltán Kutalik, Hakon Hakonarson, Shamil Sunyaev, Harrison Brand, Michael E. Talkowski, Andres Metspalu, Mari Nelis, and Lili Milani
Subjects: DNA Copy Number Variations, Genome, Human, Gene Dosage, Humans, Haploinsufficiency, General Biochemistry, Genetics and Molecular Biology
Abstract: Rare copy-number variants (rCNVs) include deletions and duplications that occur infrequently in the global human population and can confer substantial risk for disease. In this study, we aimed to quantify the properties of haploinsufficiency (i.e., deletion intolerance) and triplosensitivity (i.e., duplication intolerance) throughout the human genome. We harmonized and meta-analyzed rCNVs from nearly one million individuals to construct a genome-wide catalog of dosage sensitivity across 54 disorders, which defined 163 dosage sensitive segments associated with at least one disorder. These segments were typically gene dense and often harbored dominant dosage sensitive driver genes, which we were able to prioritize using statistical fine-mapping. Finally, we designed an ensemble machine-learning model to predict probabilities of dosage sensitivity (pHaplopTriplo) for all autosomal genes, which identified 2,987 haploinsufficient and 1,559 triplosensitive genes, including 648 that were uniquely triplosensitive. This dosage sensitivity resource will provide broad utility for human disease research and clinical genetics.
Published: 2020

7. The Trans-Ancestral Genomic Architecture of Glycaemic Traits

Author: Hugoline G. de Haan, Andrew A. Hicks, Achilleas Pitsilides, Fernando Pires Hartwig, Richard A. Jensen, Matti Uusitupa, Anders Hamsten, Dennis O. Mook-Kanamori, Zorayr Arzumanyan, Betina H. Thuesen, Karin Leander, Fernando Rivideneira, Lynne E. Wagenknecht, Andrew R. Wood, Annique Claringbould, Ele Ferranni, Sölve Elmståhl, Eleanor Wheeler, Sharon L.R. Kardia, Richa Saxena, Tatijana Zemunik, Cassandra N. Spracklen, Ken K. Ong, Xiao-Ou Shu, Johannes Waage, Blair H. Smith, Rozenn N. Lemaitre, Torben Hansen, Peter K. Joshi, Lisa R. Yanek, Neil R. Robertson, Sven Bergmann, Mila Desi Anasanti, Inger Njølstad, Ananda R. Wickremasinghe, Xu Lin, Harold Snieder, Wanqing Wen, Veronique Vitart, Paul R. H. J. Timmers, Timo Saaristo, James F. Wilson, Tian Xie, Tao Huang, Rainer Rauramaa, Kei Hang, Rebecca Rohde, Li-Ching Chang, Jing Hua Zhao, Kazuya Setoh, Yasuharu Tabara, Michael Stumvoll, Mark O. Goodarzi, Igor Rudan, James B. Meigs, Jaakko Tuomilehto, Richard M. Watanabe, Ruth J. F. Loos, Reedik Mägi, Jouke-Jan Hottenga, Ozren Polasek, Michael Y. Tsai, Donald W. Bowden, Diana Kuh, Erik B. van den Akker, Yii-Der Ida Chen, Daniel I. Chasman, Weihua Zhang, Nicholette D. Palmer, Marcus E. Kleber, Anny H. Xiang, Chang-Hsun Hsieh, Alan B. Zonderman, Stefan Gustafsson, Timo A. Lakka, Brian H. Chen, Dermot F. Reilly, Francis S. Collins, Oluf Pedersen, Corri Black, Yang Hai, Zoltán Kutalik, Yoriko Heianza, Willa A. Hsueh, Vilmundur Gudnason, Robert C. Kaplan, Jun Liu, Michael A. Province, Aliki-Eleni Farmaki, Stephen S. Rich, Jian'an Luan, Erik Ingelsson, Marie Loh, Michael Preuss, Lars Lind, Stefan R. Bornstein, Mandy Vogel, Colin N. A. Palmer, Fumihiko Matsuda, Takahisa Kawaguchi, Sohee Han, Ching-Ti Liu, Young-Jin Kim, L. Southam, Sara M. Willems, Mickaël Canouil, Robert A. Scott, Marika Kaakinen, Stephan J. L. Bakker, Momoko Horikoshi, Tarunveer S. Ahluwalia, Annette Schürmann, Graciela E. Delgado, Thibaud S. Boutin, Thomas Sparsø, Sandosh Padmanabhan, Fouad Kandeel, Eco J. C. de Geus, Anubha Mahajan, Claudia Schurmann, Klaus Bønnelykke, Leslie A. Lange, Qing Duan, Rona J. Strawbridge, Dennis Raven, Gonçalo R. Abecasis, Mitsuhiro Yokota, Jani Heikkinen, Elizabeth Selvin, Audrey Y. Chu, Anke Tönjes, Marta E. Alarcón-Riquelme, Hans Bisgaard, P. Eline Slagboom, Eric Boerwinkle, Massimo Mangino, Catharina A. Hartman, Geltrude Mingrone, Lenore J. Launer, Michael Boehnke, Emil V. R. Appel, Niels Grarup, Arushi Varshney, Archie Campbell, Kari E. North, W. Craig Johnson, Inês Barroso, Ya X. Wang, Carola Marzi, Anuj Goel, Eleftheria Zeggini, Lu Qi, Yasumasa Ohyagi, Tien Yin Wong, Tanja G. M. Vrijkotte, Gudny Eiriksdottir, Harald Grallert, Ishminder K. Kooner, Trevor A. Mori, Jagadish Vangipurapu, Laura J Corbin, Tomohiro Katsuya, Wen B. Wei, Segun Fatumo, Debashree Ray, Annette Peters, Lori L. Bonnycastle, Ilja M. Nolte, M. Arfan Ikram, Manjinder S. Sandhu, Marit E. Jørgensen, Christian Herder, Damia Noce, Sarah C. Nelson, Chien-Hsiun Chen, Heather M. Stringham, Yong-Bing Xiang, Bruce M. Psaty, Alain G. Bertoni, Gaëlle Marenne, Timothy M. Frayling, Jose C. Florez, Penny Gordon-Larsen, Yu-Tang Gao, Abhishek Nag, Damiano Baldassarre, J. Wouter Jukema, Wei Huang, Yi-Cheng Chang, Albertine J. Oldehinkel, Xiaoshuai Zhang, Yujie Wang, Shaofeng Huo, Xueling Sim, Norihiro Kato, Bernhard O. Böhm, Lorraine Southam, Mari Nelis, Gonneke Willemsen, Laura J. Rasmussen-Torvik, Philippe Froguel, Charumathi Sabanayagam, Leif Groop, Loic Yengo, Shi Jinxiu, Adolfo Correa, Serena Sanna, Arne Astrup, Teemu Kuulasmaa, Symen Ligthart, Shih-Yi Lin, David J. Porteous, Harry Campbell, Peter Vollenweider, Mark J. Caulfield, Kristi Läll, Anne Ndungu, Carl D. Langefeld, Tanya M. Teslovich, Heikki A. Koistinen, Ying Wu, Mattias Frånberg, D.I. Boomsma, Lawrence F. Bielak, Diana van Heemst, Peter Kovacs, Markku Laakso, Leslie J. Raffel, Katharina E. Schraut, Noël P. Burtt, Michiya Igase, Craig E. Pennell, Claudia Langenberg, Huaixing Li, Teresa Tusie, Laura M. Raffield, Jorgen Engmann, Stephen C. J. Parker, Michele K. Evans, Chaolong Wang, Rico Rueedi, Jianjun Liu, Pankow S. James, Hortensia Moreno-Macías, Fumihiko Takeuchi, Cornelia M. van Duijn, Sanghoon Moon, Susan R. Heckbert, Thomas A. Buchanan, Ko Willems van Dijk, Toru Nabika, May E. Montasser, Caroline Hayward, Jie Yao, Aaron Leong, Antje Körner, Jouko Saramies, Jost B. Jonas, Pim van der Harst, Naveed Sattar, Helen R. Warren, Alice Stanton, Yen-Feng Chiu, Kumaraswamy Naidu Chitrala, Mi Yeong Hwang, Jin Fang Chai, Alicia Huerta-Chagoya, Anette P. Gjesing, Ching-Yu Cheng, Debbie A Lawlor, Simin Liu, Man Li, Ivana Kolcic, Erwin P. Bottinger, Andrew Wong, Stella Trompet, Heming Wang, Jirong Long, Xiuqing Guo, Jeffrey R. O'Connell, Meena Kumari, Sirkka Keinänen-Kiukaanniemi, Rita R. Kalyani, Bengt Sennblad, Mohammad Hadi Zafarmand, Kent D. Taylor, Katherine A. Kentistou, Carol A. Wang, Shuiqing Lai, Patricia B. Munroe, Patricia A. Peyser, Lawrence J. Beilin, Niek Verweij, Inga Prokopenko, Brian E. Cade, Patrik K. E. Magnusson, John C. Chambers, Tamar Sofer, Ping An, Matthias Blüher, Isobel D. Stewart, Alexander P. Reiner, Anna L. Gloyn, Simon P. Mooijaart, Tim D. Spector, Paul W. Franks, Wei Zhao, Andres Metspalu, Wieland Kiess, Kathleen A. Ryan, Astrid van Hylckama Vlieg, Jaana Lindström, Wei Zheng, E. Shyong Tai, Josée Dupuis, Nanette R. Lee, Laura J. Scott, Nicholas J. Timpson, George Dedoussis, Mark I. McCarthy, Tatsuaki Matsubara, Carlos Lorenzo, Denis Rybin, Luigi Ferruci, Chelsea K. Raulerson, Mika Kivimäki, Paul M. Ridker, Jer-Yuarn Wu, Shufa Du, Jaeyoung Hong, Linda S. Adair, Tin Louie, Valeriya Lyssenko, Susan Redline, Kelvin Lam, Qibin Qi, H. Janaka de Silva, Jana V. van Vliet-Ostaptchouk, Peter J. van der Most, Sahoko Ichihara, Nicholas J. Wareham, Ayse Demirkan, Francesco Cucca, Allan Linneberg, Rob M. van Dam, Claire J. Steves, Liang Sun, Albert V. Smith, Raymond Noordam, Tom Wilsgaard, Winfried März, Jung Ho Gong, Matt J. Neville, Jerry L. Nadler, Giorgio Pistis, Karen L. Mohlke, Bruna Gigante, Jennifer A. Brody, Andrew P. Morris, Marie Lauzon, Peter E. H. Schwarz, Bernardo L. Horta, Xiaoran Chai, Ji Chen, Peter S. Sever, Thorkild I. A. Sørensen, André G. Uitterlinden, Javier Gayán, Elena Tremoli, Girish N. Nadkarni, Najaf Amin, Hugh Watkins, Johanna Kuusisto, Jingyi Tan, Sameline Grimsgaard, Bong-Jo Kim, Kerrin S. Small, Jill M. Norris, Cecilia M. Lindgren, Richard N. Bergman, Mark Walker, Henrik Vestergaard, Larissa Aviles-Santa, Jing He, Masahiro Nakatochi, Peter P. Pramstaller, Chiea Chuen Khor, Ruifang Li-Gao, Qiuyin Cai, Neil Schneiderman, Kevin Sandow, Jaspal S. Kooner, Carlos A. Aguilar-Salinas, Peitao Wu, Jerome I. Rotter, Kathryn Roll, Frits R. Rosendaal, Diane M. Becker, Marian Beekman, Claudia P. Cabrera, Nan Wang, Franco Giulianini, Tao Wang, Honglan Li, Abbas Dehghan, Christian Fuchsberger, and Pontiano Kaleebu
Subjects: 0303 health sciences, medicine.medical_specialty, business.industry, Type 2 diabetes, medicine.disease, Fasting insulin, Fasting glucose, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, Diabetes mellitus, medicine, Genomic architecture, business, Glycated haemoglobin, 030217 neurology & neurosurgery, 030304 developmental biology, Genetic association
Abstract: Glycaemic traits are used to diagnose and monitor type 2 diabetes, and cardiometabolic health. To date, most genetic studies of glycaemic traits have focused on individuals of European ancestry. Here, we aggregated genome-wide association studies in up to 281,416 individuals without diabetes (30% non-European ancestry) with fasting glucose, 2h-glucose post-challenge, glycated haemoglobin, and fasting insulin data. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P-8), 80% with no significant evidence of between-ancestry heterogeneity. Analyses restricted to European ancestry individuals with equivalent sample size would have led to 24 fewer new loci. Compared to single-ancestry, equivalent sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase understanding of diabetes pathophysiology by use of trans-ancestry studies for improved power and resolution.
Published: 2020

8. Genome-wide association study identifies 48 common genetic variants associated with handedness

Author: Christian Gieger, Teemu Palviainen, Bettina Konte, Peter P. Pramstaller, Aarno Palotie, Elisabeth Widen, Monique M.B. Breteler, Caroline Hayward, Xin Li, Tim D. Spector, Jing Hua Zhao, John M. Starr, David M. Evans, Nicholas G. Martin, Wendy L. McArdle, Nicole Soranzo, Mads Melbye, Peter Kraft, André G. Uitterlinden, Beate St Pourcain, Massimo Mangino, Daniel I. Chasman, Jacques S. Beckmann, Gabriel Cuellar Partida, George Davey Smith, Cecilia M. Lindgren, Johan G. Eriksson, Alan F. Wright, Kauko Heikkilä, Eva Albrecht, Gudmar Thorleifsson, Mari Nelis, Nicholas Eriksson, Dawn M. Waterworth, Leena Peltonen, Frank J. A. van Rooij, Jari Lahti, Maris Teder-Laving, Igor Rudan, Annette M. Hartmann, Guillaume Paré, Ole A. Andreassen, Mohammad Arfan Ikram, Stacy Steinberg, Bjarke Feenstra, Peter Vollenweider, Sarah E. Medland, Brenda W.J.H. Penninx, Mark I. McCarthy, Jordan W. Smoller, Fazil Aliev, Joel N. Hirschhorn, Dan Rujescu, J.M. Vink, Dorret I. Boomsma, Harry Campbell, Pedro Marques-Vidal, David A. Hinds, Tõnu Esko, Ruth J. F. Loos, Zoltán Kutalik, Jouke-Jan Hottenga, Reedik Mägi, Dale R. Nyholt, Kari Stefansson, Kevin S. O’Connell, Hreinn Stefansson, Scott Melville, Andres Metspalu, Inês Barroso, Marco P. Boks, Gail Davies, Lavinia Paternoster, Thomas Hansen, Norman Klopp, H.-Erich Wichmann, David L. Duffy, Lili Milani, Heather A. Boyd, Michelle Luciano, Benjamin M. Neale, Margaret J. Wright, Fernando Rivadeneira, Liang-Dar Hwang, Scott D. Gordon, Jiali Han, Jennifer E. Huffman, Danielle M. Dick, Roel A. Ophoff, Ozren Polasek, Nicholas J. Wareham, Vincent Mooser, Mousheng Xu, Johannes H. Smit, Gonneke Willemsen, Ian J. Deary, Panos Deloukas, John P. Kemp, Cornelia M. van Duijn, Samuli Ripatti, Joyce Y. Tung, Eco J. C. de Geus, Cameron D. Palmer, Ina Giegling, Katri Räikkönen, Thomas Werge, Eero Vuoksimaa, Andrew A. Hicks, Inga Prokopenko, Lynn Cherkas, Sigurdur H. Magnusson, Gérard Waeber, Nicholas J. Timpson, Frank Geller, Carolina Medina-Gomez, Nicole M. Warrington, Kay-Tee Khaw, and Jaakko Kaprio
Subjects: Genetics, 0303 health sciences, 03 medical and health sciences, 0302 clinical medicine, Genetic variants, Biology, Association (psychology), Biobank, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: Handedness, a consistent asymmetry in skill or use of the hands, has been studied extensively because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and 32 studies from the International Handedness Consortium, we conducted the world’s largest genome-wide association study of handedness (1,534,836 right-handed, 194,198 (11.0%) left-handed and 37,637 (2.1%) ambidextrous individuals). We found 41 genetic loci associated with left-handedness and seven associated with ambidexterity at genome-wide levels of significance (P < 5×10−8). Tissue enrichment analysis implicated the central nervous system and brain tissues including the hippocampus and cerebrum in the etiology of left-handedness. Pathways including regulation of microtubules, neurogenesis, axonogenesis and hippocampus morphology were also highlighted. We found suggestive positive genetic correlations between being left-handed and some neuropsychiatric traits including schizophrenia and bipolar disorder. SNP heritability analyses indicated that additive genetic effects of genotyped variants explained 5.9% (95% CI = 5.8% – 6.0%) of the underlying liability of being left-handed, while the narrow sense heritability was estimated at 12% (95% CI = 7.2% – 17.7%). Further, we show that genetic correlation between left-handedness and ambidexterity is low (rg = 0.26; 95% CI = 0.08 – 0.43) implying that these traits are largely influenced by different genetic mechanisms. In conclusion, our findings suggest that handedness, like many other complex traits is highly polygenic, and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders that has been observed in multiple observational studies.
Published: 2019

9. Estimation of Genetic Correlation via Linkage Disequilibrium Score Regression and Genomic Restricted Maximum Likelihood

Author: Guiyan Ni, Gerhard Moser, Naomi R. Wray, S. Hong Lee, Stephan Ripke, Benjamin M. Neale, Aiden Corvin, James T.R. Walters, Kai-How Farh, Peter A. Holmans, Phil Lee, Brendan Bulik-Sullivan, David A. Collier, Hailiang Huang, Tune H. Pers, Ingrid Agartz, Esben Agerbo, Margot Albus, Madeline Alexander, Farooq Amin, Silviu A. Bacanu, Martin Begemann, Richard A. Belliveau, Judit Bene, Sarah E. Bergen, Elizabeth Bevilacqua, Tim B. Bigdeli, Donald W. Black, Richard Bruggeman, Nancy G. Buccola, Randy L. Buckner, William Byerley, Wiepke Cahn, Guiqing Cai, Dominique Campion, Rita M. Cantor, Vaughan J. Carr, Noa Carrera, Stanley V. Catts, Kimberly D. Chambert, Raymond C.K. Chan, Ronald Y.L. Chen, Eric Y.H. Chen, Wei Cheng, Eric F.C. Cheung, Siow Ann Chong, C. Robert Cloninger, David Cohen, Nadine Cohen, Paul Cormican, Nick Craddock, James J. Crowley, David Curtis, Michael Davidson, Kenneth L. Davis, Franziska Degenhardt, Jurgen Del Favero, Ditte Demontis, Dimitris Dikeos, Timothy Dinan, Srdjan Djurovic, Gary Donohoe, Elodie Drapeau, Jubao Duan, Frank Dudbridge, Naser Durmishi, Peter Eichhammer, Johan Eriksson, Valentina Escott-Price, Laurent Essioux, Ayman H. Fanous, Martilias S. Farrell, Josef Frank, Lude Franke, Robert Freedman, Nelson B. Freimer, Marion Friedl, Joseph I. Friedman, Menachem Fromer, Giulio Genovese, Lyudmila Georgieva, Ina Giegling, Paola Giusti-Rodríguez, Stephanie Godard, Jacqueline I. Goldstein, Vera Golimbet, Srihari Gopal, Jacob Gratten, Lieuwe de Haan, Christian Hammer, Marian L. Hamshere, Mark Hansen, Thomas Hansen, Vahram Haroutunian, Annette M. Hartmann, Frans A. Henskens, Stefan Herms, Joel N. Hirschhorn, Per Hoffmann, Andrea Hofman, Mads V. Hollegaard, David M. Hougaard, Masashi Ikeda, Inge Joa, Antonio Juliá, René S. Kahn, Luba Kalaydjieva, Sena Karachanak-Yankova, Juha Karjalainen, David Kavanagh, Matthew C. Keller, James L. Kennedy, Andrey Khrunin, Yunjung Kim, Janis Klovins, James A. Knowles, Bettina Konte, Vaidutis Kucinskas, Zita Ausrele Kucinskiene, Hana Kuzelova-Ptackova, Anna K. Kähler, Claudine Laurent, Jimmy Lee Chee Keong, Sophie E. Legge, Bernard Lerer, Miaoxin Li, Tao Li, Kung-Yee Liang, Jeffrey Lieberman, Svetlana Limborska, Carmel M. Loughland, Jan Lubinski, Jouko Lönnqvist, Milan Macek, Patrik K.E. Magnusson, Brion S. Maher, Wolfgang Maier, Jacques Mallet, Sara Marsal, Manuel Mattheisen, Morten Mattingsda, Robert W. McCarley, Colm McDonald, Andrew M. McIntosh, Sandra Meier, Carin J. Meijer, Bela Melegh, Ingrid Melle, Raquelle I. Mesholam-Gately, Andres Metspalu, Patricia T. Michie, Lili Milani, Vihra Milanova, Younes Mokrab, Derek W. Morris, Ole Mors, Kieran C. Murphy, Robin M. Murray, Inez Myin-Germeys, Bertram Müller-Myhsok, Mari Nelis, Igor Nenadic, Deborah A. Nertney, Gerald Nestadt, Kristin K. Nicodemus, Liene Nikitina-Zake, Laura Nisenbaum, Annelie Nordin, Eadbhard O’Callaghan, Colm O’Dushlaine, F. Anthony O’Neill, Sang-Yun Oh, Ann Olinc, Line Olsen, Jim Van Os, Christos Pantelis, George N. Papadimitriou, Sergi Papio, Elena Parkhomenko, Michele T. Pato, Tiina Paunio, Milica Pejovic-Milovancevic, Diana O. Perkins, Olli Pietiläinenl, Jonathan Pimm, Andrew J. Pocklington, John Powell, Alkes Price, Ann E. Pulver, Shaun M. Purcell, Digby Quested, Henrik B. Rasmussen, Abraham Reichenberg, Mark A. Reimers, Alexander L. Richards, Joshua L. Roffman, Panos Roussos, Douglas M. Ruderfer, Veikko Salomaa, Alan R. Sanders, Ulrich Schall, Christian R. Schubert, Thomas G. Schulze, Sibylle G. Schwab, Edward M. Scolnick, Rodney J. Scott, Larry J. Seidman, Jianxin Shi, Engilbert Sigurdsson, Teimuraz Silagadze, Jeremy M. Silverman, Kang Sim, Petr Slominsky, Jordan W. Smoller, Hon-Cheong So, Chris C.A. Spencer, Eli A. Stah, Hreinn Stefansson, Stacy Steinberg, Elisabeth Stogmann, Richard E. Straub, Eric Strengman, Jana Strohmaier, T. Scott Stroup, Mythily Subramaniam, Jaana Suvisaari, Dragan M. Svrakic, Jin P. Szatkiewicz, Erik Söderman, Srinivas Thirumalai, Draga Toncheva, Sarah Tosato, Juha Veijola, John Waddington, Dermot Walsh, Dai Wang, Qiang Wang, Bradley T. Webb, Mark Weiser, Dieter B. Wildenauer, Nigel M. Williams, Stephanie Williams, Stephanie H. Witt, Aaron R. Wolen, Emily H.M. Wong, Brandon K. Wormley, Hualin Simon Xi, Clement C. Zai, Xuebin Zheng, Fritz Zimprich, Kari Stefansson, Peter M. Visscher, Rolf Adolfsson, Ole A. Andreassen, Douglas H.R. Blackwood, Elvira Bramon, Joseph D. Buxbaum, Anders D. Børglum, Sven Cichon, Ariel Darvasi, Enrico Domenici, Hannelore Ehrenreich, Tõnu Esko, Pablo V. Gejman, Michael Gill, Hugh Gurling, Christina M. Hultman, Nakao Iwata, Assen V. Jablensky, Erik G. Jönsson, Kenneth S. Kendler, George Kirov, Jo Knight, Todd Lencz, Douglas F. Levinson, Qingqin S. Li, Jianjun Liu, Anil K. Malhotra, Steven A. McCarrol, Andrew McQuillin, Jennifer L. Moran, Preben B. Mortensen, Bryan J. Mowry, Markus M. Nöthen, Roel A. Ophoff, Michael J. Owen, Aarno Palotie, Carlos N. Pato, Tracey L. Petryshen, Danielle Posthuma, Marcella Rietsche, Brien P. Riley, Dan Rujescu, Pak C. Sham, Pamela Sklar, David St Clair, Daniel R. Weinberger, Jens R. Wendland, Thomas Werge, Mark J. Daly, Patrick F. Sullivan, Michael C. O’Donovan, APH - Mental Health, ANS - Complex Trait Genetics, Adult Psychiatry, Ni, Guiyan, Moser, Gerhard, Wray, Naomi R, Lee, S Hong, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Amsterdam Neuroscience - Complex Trait Genetics, Complex Trait Genetics, Clinicum, Department of Psychiatry, and HUS Psychiatry
Subjects: 0301 basic medicine, Linkage disequilibrium, Schizophrenia/genetics, INFORMATION, Restricted maximum likelihood, Inheritance Patterns, linkage disequilibrium score regression, Bioinformatics, Medical and Health Sciences, 3124 Neurology and psychiatry, Linkage Disequilibrium, biasedness, 0302 clinical medicine, Statistics, Databases, Genetic, WIDE ASSOCIATION, Genetics(clinical), PARTITIONING HERITABILITY, Genetics (clinical), Genetics & Heredity, education.field_of_study, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Likelihood Functions, Genome, Body Height/genetics, accuracy, Regression analysis, Single Nucleotide, Biological Sciences, Polymorphism, Single Nucleotide/genetics, genetic correlation, Regression, STATISTICS, genomic restricted maximum likelihood, Mental Health, Phenotype, Regression Analysis, COMPLEX HUMAN TRAITS, Single Nucleotide/genetics, Human, Adult, SUSCEPTIBILITY LOCI, Genotype, SNP heritability, body mass index, genome-wide SNPs, height, schizophrenia, Population, Haplotypes/genetics, Biology, Genetic correlation, Polymorphism, Single Nucleotide, 03 medical and health sciences, Databases, Genetic, ddc:570, Report, Genetics, Humans, Linkage Disequilibrium/genetics, Computer Simulation, Polymorphism, education, linkage disequilibrium score regression (LDSC), Genome, Human, Human Genome, genetic architecture, Genetic architecture, Body Height, Brain Disorders, Inheritance Patterns/genetics, BODY-MASS INDEX, 030104 developmental biology, Haplotypes, Sample size determination, Schizophrenia, 3111 Biomedicine, HUMAN HEIGHT, 030217 neurology & neurosurgery
Abstract: J. Lönnqvist on työryhmän Psychiat Genomics Consortium jäsen. Genetic correlation is a key population parameter that describes the shared genetic architecture of complex traits and diseases. It can be estimated by current state-of-art methods, i.e., linkage disequilibrium score regression (LDSC) and genomic restricted maximum likelihood (GREML). The massively reduced computing burden of LDSC compared to GREML makes it an attractive tool, although the accuracy (i.e., magnitude of standard errors) of LDSC estimates has not been thoroughly studied. In simulation, we show that the accuracy of GREML is generally higher than that of LDSC. When there is genetic heterogeneity between the actual sample and reference data from which LD scores are estimated, the accuracy of LDSC decreases further. In real data analyses estimating the genetic correlation between schizophrenia (SCZ) and body mass index, we show that GREML estimates based on similar to 150,000 individuals give a higher accuracy than LDSC estimates based on similar to 400,000 individuals (from combinedmeta-data). A GREML genomic partitioning analysis reveals that the genetic correlation between SCZ and height is significantly negative for regulatory regions, which whole genome or LDSC approach has less power to detect. We conclude that LDSC estimates should be carefully interpreted as there can be uncertainty about homogeneity among combined meta-datasets. We suggest that any interesting findings from massive LDSC analysis for a large number of complex traits should be followed up, where possible, with more detailed analyses with GREML methods, even if sample sizes are lesser.
Published: 2017

10. Age at first birth in women is genetically associated with increased risk of schizophrenia

Author: Fritz Zimprich, Manuel Mattheisen, Edward M. Scolnick, Ayman H. Fanous, Henrik B. Rasmussen, Steven A. McCarroll, Ingrid Agartz, Carmel M. Loughland, Aiden Corvin, Ann Olincy, Anders D. Børglum, F. Anthony O'Neill, T. Scott Stroup, Elizabeth Bevilacqua, Sandra Meier, Ulrich Schall, Jouko Lönnqvist, Jianxin Shi, C. Robert Cloninger, Judit Bene, Veikko Salomaa, George N. Papadimitriou, Milica Pejovic-Milovancevic, Béla Melegh, Kari Stefansson, Brendan Bulik-Sullivan, Janis Klovins, Enrico Domenici, Sibylle G. Schwab, Dai Wang, Assen Jablensky, Mari Nelis, Sang Yun Oh, Peter Holmans, Aaron R. Wolen, Hualin Simon Xi, Eric Strengman, Bryan J. Mowry, Michael Gill, Kung Yee Liang, William Byerley, Rolf Adolfsson, Hugh Gurling, Joseph I. Friedman, Andrew Pocklington, Brien P. Riley, Engilbert Sigurdsson, Benjamin M. Neale, Miaoxin Li, Michael Davidson, Bernard Lerer, Michele T. Pato, Xuebin Zheng, Patrick F. Sullivan, Frans Henskens, Madeline Alexander, Andrew M. McIntosh, Inez Myin-Germeys, Draga Toncheva, Liene Nikitina-Zake, Kenneth S. Kendler, Carin J. Meijer, Robin M. Murray, Richard E. Straub, Ann E. Pulver, Menachem Fromer, Derek W. Morris, Douglas M. Ruderfer, Mythily Subramaniam, Paul Cormican, Lyudmila Georgieva, Giulio Genovese, Brion S. Maher, Stanley V. Catts, David St Clair, Robert W. McCarley, David Cohen, Nancy G. Buccola, Dan Rujescu, Carlos N. Pato, Kristin K. Nicodemus, Josef Frank, Claudine Laurent, Dominique Campion, Guiyan Ni, James L. Kennedy, Sena Karachanak-Yankova, Nicholas John Craddock, Peter M. Visscher, Valentina Escott-Price, Jeffrey A. Lieberman, Deborah A. Nertney, Bertram Müller-Myhsok, Marcella Rietschel, Dimitris Dikeos, Stephanie Godard, Stephanie Williams, Andres Metspalu, John L. Waddington, Sophie E. Legge, Roel A. Ophoff, Jonathan Pimm, Richard Bruggeman, Tim B. Bigdeli, Gerald Nestadt, Mark Weiser, Kieran C. Murphy, Eric F.C. Cheung, Kang Sim, Jordan W. Smoller, David J. Kavanagh, Inge Joa, Jens R. Wendland, Thomas G. Schulze, Richard A. Belliveau, Sarah E. Bergen, Ditte Demontis, David Curtis, Todd Lencz, Danielle Posthuma, René S. Kahn, Lili Milani, Randy L. Buckner, Jianjun Liu, Petr Slominsky, Wiepke Cahn, Hana Kuzelova-Ptackova, Sergi Papiol, Tune H. Pers, Stephan Ripke, Rita M. Cantor, Ariel Darvasi, Christina M. Hultman, Larry J. Seidman, Eli A. Stahl, David A. Collier, Michael Conlon O'Donovan, Svetlana A. Limborska, James T.R. Walters, Farooq Amin, Noa Carrera, Ronald Y.L. Chen, Pablo V. Gejman, Joel N. Hirschhorn, Zita Ausrele Kucinskiene, Michael John Owen, Ina Giegling, Stephanie H. Witt, Timothy G. Dinan, Margot Albus, Wei Cheng, Marian L. Hamshere, Markus M. Nöthen, Thomas Werge, Guiqing Cai, Raquelle I. Mesholam-Gately, Annette M. Hartmann, Ingrid Melle, Ole A. Andreassen, Preben Bo Mortensen, Hannelore Ehrenreich, Tiina Paunio, James A. Knowles, Pak C. Sham, Marion Friedl, Teimuraz Silagadze, Dermot Walsh, Emily H. M. Wong, Igor Nenadic, Matthew C. Keller, John Powell, Naomi R. Wray, Patricia T. Michie, Bradley T. Webb, Lude Franke, Mark Hansen, Masashi Ikeda, Sven Cichon, Elvira Bramon, Frank Dudbridge, Erik G. Jönsson, Annelie Nordin, Wolfgang Maier, Peter Eichhammer, Christian R. Schubert, J. Mallet, Jacob Gratten, Andrey Khrunin, Jacqueline I. Goldstein, Panos Roussos, Pamela Sklar, Diana O. Perkins, Srdjan Djurovic, Phil Lee, Elodie Drapeau, Douglas F. Levinson, Nadine Cohen, Luba Kalaydjieva, Brandon Wormley, Tao Li, Tõnu Esko, Alexander Richards, Srihari Gopal, Jubao Duan, Anil K. Malhotra, Elisabeth Stögmann, Gary Donohoe, Kimberly Chambert, Sara Marsal, Hreinn Stefansson, Jo Knight, Ole Mors, Per Hoffmann, Dieter B. Wildenauer, James J. Crowley, Srinivas Thirumalai, Vahram Haroutunian, A. Hofman, Hailiang Huang, Thomas Hansen, Daniel R. Weinberger, Andrew McQuillin, Vaughan J. Carr, Vaidutis Kučinskas, Jimmy Lee Chee Keong, Digby Quested, Aarno Palotie, Robert Freedman, Hon-Cheong So, Jennifer L. Moran, Donald W. Black, Mark Reimers, Abraham Reichenberg, Jurgen Del Favero, Paola Giusti-Rodríguez, Tracey L. Petryshen, Olli Pietiläinen, Franziska Degenhardt, Laurent Essioux, Esben Agerbo, Qiang Wang, Jana Strohmaier, Siow Ann Chong, Johan G. Eriksson, Martin Begemann, Younes Mokrab, Colm McDonald, Silviu Alin Bacanu, Martilias S. Farrell, Christos Pantelis, Kai How Farh, Line Olsen, Naser Durmishi, Antonio Julià, Stefan Herms, Qingqin S. Li, Bettina Konte, George Kirov, Rodney J. Scott, Nelson B. Freimer, Mads V. Hollegaard, Shaun Purcell, Erik Söderman, Dragan M. Svrakic, Patrik K. E. Magnusson, Douglas Blackwood, Jin P. Szatkiewicz, Sang Hong Lee, Yunjung Kim, Colm O'Dushlaine, Morten Mattingsdal, Jim van Os, Sarah Tosato, Milan Macek, Joshua L. Roffman, Jan Lubinski, Eadbhard O'Callaghan, Juha Karjalainen, Vera Golimbet, Anna K. Kähler, Clement C. Zai, Nigel Williams, Joseph D. Buxbaum, Laura Nisenbaum, Eric Y.H. Chen, David M. Hougaard, Jaana Suvisaari, Chris C. A. Spencer, Alan R. Sanders, Alkes L. Price, Vihra Milanova, Juha Veijola, Christian Hammer, Raymond C.K. Chan, Stacy Steinberg, Nakao Iwata, Jeremy M. Silverman, Mark J. Daly, Elena Parkhomenko, Kenneth L. Davis, Lieuwe de Haan, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Reproduction & Development (AR&D), Kučinskas, Vaidutis, Kučinskienė, Zita Aušrelė, Ni, Guiyan, Gratten, Jacob, Wray, Naomi R, Lee, Sang Hong, Germeys, Inez, Complex Trait Genetics, Háskóli Íslands, University of Iceland, Child and Adolescent Psychiatry / Psychology, Research Programs Unit, Diabetes and Obesity Research Program, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, University Management, Department of Psychiatry, Center for Population, Health and Society, Department of Public Health, Centre of Excellence in Complex Disease Genetics, Research Programme of Molecular Medicine, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, and Genomics of Neurological and Neuropsychiatric Disorders
Subjects: 0301 basic medicine, Multifactorial Inheritance, PATERNAL-AGE, 3124 Neurology and psychiatry, COMMON SNPS, fluids and secretions, 0302 clinical medicine, CHILD, Risk Factors, Pregnancy, 2.1 Biological and endogenous factors, Medicine, Aetiology, Pediatric, PROPORTION, Schizophrenia Working Group of the Psychiatric Genomics Consortium, 0303 health sciences, Multidisciplinary, PSYCHIATRIC-DISORDERS, BIPOLAR DISORDER, Biobank, 3. Good health, AFB, Mental Health, Schizophrenia, Female, Erfðarannsóknir, Psychosocial, TRAITS, schizophrenia, age at birth, AFB, Maternal Age, Adult, age at first birth in women, genetic association, Offspring, Science, Genetic correlation, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Geðklofi, Genetics, age at birth, Humans, Genetic Predisposition to Disease, Bipolar disorder, General, Biology, Genetic association study, 030304 developmental biology, Genetic association, business.industry, Genetic heterogeneity, Prevention, average aged parents, Parturition, SCORE REGRESSION, bacterial infections and mycoses, medicine.disease, Mental health, Brain Disorders, respiratory tract diseases, schizophrenia, Good Health and Well Being, 030104 developmental biology, younger and older parents, DE-NOVO MUTATIONS, ddc:000, Human medicine, business, 030217 neurology & neurosurgery, Demography
Abstract: Publisher's version (útgefin grein), Previous studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is −0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health., This research is supported by the Australian National Health and Medical Research Council (1080157, 1087889, 1103418, 1127440), and the Australian Research Council (DP160102126, FT160100229). This research has been conducted using the UK Biobank Resource. UK Biobank (http://www.ukbiobank.ac.uk) Research Ethics Committee (REC) approval number is 11/NW/0382. Our reference number approved by UK Biobank is 14575.
Published: 2017

11. Shared and Unique Components of Human Population Structure and Genome-Wide Signals of Positive Selection in South Asia

Author: Gyaneshwer Chaubey, Irene Gallego Romero, Reedik Mägi, Ene Metspalu, Mari Nelis, Maido Remm, Richard Villems, Toomas Kivisild, Mait Metspalu, Bayazit Yunusbayev, Georgi Hudjashov, Chandana Basu Mallick, Kumarasamy Thangaraj, Ramasamy Pitchappan, and Lalji Singh
Subjects: Asia, Heredity, Demographic history, Ethnic group, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, 0302 clinical medicine, Effective population size, Genetics, Humans, Genetic Predisposition to Disease, Genetics(clinical), Selection, Genetic, Genetics (clinical), Selection (genetic algorithm), 030304 developmental biology, Principal Component Analysis, 0303 health sciences, Genetic diversity, Models, Genetic, Haplotype, Lipid Metabolism, Phylogeography, Diabetes Mellitus, Type 2, Haplotypes, Erratum, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: South Asia harbors one of the highest levels genetic diversity in Eurasia, which could be interpreted as a result of its long-term large effective population size and of admixture during its complex demographic history. In contrast to Pakistani populations, populations of Indian origin have been underrepresented in previous genomic scans of positive selection and population structure. Here we report data for more than 600,000 SNP markers genotyped in 142 samples from 30 ethnic groups in India. Combining our results with other available genome-wide data, we show that Indian populations are characterized by two major ancestry components, one of which is spread at comparable frequency and haplotype diversity in populations of South and West Asia and the Caucasus. The second component is more restricted to South Asia and accounts for more than 50% of the ancestry in Indian populations. Haplotype diversity associated with these South Asian ancestry components is significantly higher than that of the components dominating the West Eurasian ancestry palette. Modeling of the observed haplotype diversities suggests that both Indian ancestry components are older than the purported Indo-Aryan invasion 3,500 YBP. Consistent with the results of pairwise genetic distances among world regions, Indians share more ancestry signals with West than with East Eurasians. However, compared to Pakistani populations, a higher proportion of their genes show regionally specific signals of high haplotype homozygosity. Among such candidates of positive selection in India are MSTN and DOK5, both of which have potential implications in lipid metabolism and the etiology of type 2 diabetes.
Published: 2011

12. Balanced reciprocal translocation t(5;13)(q33;q12) and 9q31.1 microduplication in a man suffering from infertility and pollinosis

Author: Paul Korrovits, Ruth Mikelsaar, Ants Kurg, Ranno Rätsep, Mari Nelis, Olga Žilina, and Maie Väli
Subjects: Adult, Male, Infertility, TUBA3C Gene, Inheritance Patterns, Abnormal Karyotype, Chromosomal translocation, Haploinsufficiency, Biology, Polymorphism, Single Nucleotide, Genomic Instability, Translocation, Genetic, Male infertility, Abnormal sperm morphology, Tubulin, Chromosome Duplication, Gene duplication, Genetics, medicine, Humans, Infertility, Male, Sperm motility, Chromosomes, Human, Pair 13, Sperm Count, Rhinitis, Allergic, Seasonal, General Medicine, medicine.disease, Spermatozoa, Sperm Motility, Chromosomes, Human, Pair 5, Chromosomes, Human, Pair 9
Abstract: We describe the first case of two chromosomal abnormalities, balanced reciprocal translocation t(5;13)(q33;q12.1) and a microduplication in the region 9q31.1, in a man suffering from infertility and pollinosis. In the region 13q12.1 is located the TUBA3C (tubulin, alpha 3c) gene, which plays an important dynamic role in the motility of flagella. This case might support the opinion that haploinsufficiency of the TUBA3C gene could be the cause of sperm immotility and abnormal sperm morphology, resulting in infertility in the patient. Single-nucleotide polymorphism (SNP) array analysis revealed a novel 9q31.1 microduplication inherited from both parents, which contributes to the genomic instability.
Published: 2011

13. Hundreds of variants clustered in genomic loci and biological pathways affect human height

Author: Vilmundur Gudnason, Robert J. Weyant, Robert C. Kaplan, Jeffrey R. O'Connell, Panos Deloukas, Barbara McKnight, Alessandro De Grandi, Gert-Jan B. van Ommen, Eric Boerwinkle, Liming Liang, Douglas F. Levinson, Richard B. Hayes, Mark I. McCarthy, Andrew P. Morris, Joel N. Hirschhorn, Jaakko Kaprio, Nilesh J. Samani, Inke R. König, Frank B. Hu, Nicholas J. Wareham, Ozren Polasek, Michael C. Turchin, Daniel F. Gudbjartsson, Wilmar Igl, Vincent Mooser, Aki S. Havulinna, Themistocles L. Assimes, Cameron D. Palmer, Lachlan J. M. Coin, Eva Albrecht, Hana Lango Allen, Inês Barroso, Eco J. C. de Geus, H.-Erich Wichmann, Michael A. Province, Sarah H. Wild, Patricia B. Munroe, Jeanette Erdmann, Mattias Lorentzon, Michael Preuss, Nelson B. Freimer, Mika Kähönen, Tushar Bhangale, Nicole L. Glazer, Markku S. Nieminen, Andrew A. Hicks, Jonathan Tyrer, Grant W. Montgomery, Ruth J. F. Loos, Shaun Purcell, Manfred Kayser, Marjo-Riitta Järvelin, Guillaume Paré, Terho Lehtimäki, Irene Pichler, Ida Surakka, Tõnu Esko, Peter Kraft, Talin Haritunians, Juha Sinisalo, Mari Nelis, Veronique Vitart, Alan R. Sanders, Alistair S. Hall, Carlos Iribarren, Mark E. Cooper, André G. Uitterlinden, Peter Kovacs, David Schlessinger, Florian Ernst, Marja-Liisa Lokki, M. Juhani Junttila, Martin Ridderstråle, Jorma Viikari, Inga Prokopenko, Christopher J. O'Donnell, Jennie Hui, Aila Rissanen, Gonçalo R. Abecasis, Jouke-Jan Hottenga, Tomi Pastinen, Kevin B. Jacobs, Jan Smit, Kristin G. Ardlie, Niina Pellikka, Neil R. Robertson, Martina Müller, John F. Peden, Mary F. Feitosa, Thomas W. Winkler, Kari Stefansson, Jianjun Liu, Jaana Laitinen, Shen Haiqing, Martin Farrall, Nilanjan Chatterjee, Eleanor Wheeler, Tamara B. Harris, Åsa Johansson, Anders Hamsten, Elizabeth K. Speliotes, Larry D. Atwood, Valgerdur Steinthorsdottir, Elin Grundberg, Nicole Soranzo, Anna-Liisa Hartikainen, Devin Absher, Cecilia M. Lindgren, Rany M. Salem, Lorena Citterio, Karol Estrada, Sven Bergmann, Tony Kwan, Thomas Meitinger, Alan F. Wright, Richard N. Bergman, Sailaja Vedantam, Kirsi H. Pietiläinen, Lina Zgaga, Anne U. Jackson, Stefan Schreiber, Ju-Hyun Park, Nicola Glorioso, Jianxin Shi, Najaf Amin, Dale R. Nyholt, Lenore J. Launer, Heribert Schunkert, Thomas Quertermous, Mari Liis Tammesoo, Dorret I. Boomsma, Harry Campbell, Albert V. Smith, Andrew R. Wood, Caroline S. Fox, Paavo Zitting, Gabrielle Boucher, Alex N. Parker, Jennifer G. Sambrook, Joyce B. J. van Meurs, Heather M. Stringham, Marjolein J. Peters, Sekar Kathiresan, Elisabeth Widen, Caroline Hayward, Tim D. Spector, Dawn M. Waterworth, Carlo Rivolta, Antti Jula, Albert Hofman, Hugh Watkins, Wendy L. McArdle, Roberto Elosua, Markku Koiranen, Paul M. Ridker, Iris M. Heid, Lee M. Kaplan, Brenda W.J.H. Penninx, Peter M. Visscher, Claes Ohlsson, Per Hall, Benjamin F. Voight, Ben A. Oostra, Anna F. Dominiczak, Martin den Heijer, Andrea Maschio, Quince Gibson, Peter P. Pramstaller, Nigel W. Rayner, Carsten Oliver Schmidt, Toby Johnson, Henrik Grönberg, M. Carola Zillikens, Alan R. Shuldiner, Cornelia M. van Duijn, Samuli Ripatti, Erik Ingelsson, John R. Thompson, Stephen J. Chanock, Johannes Kettunen, David J. Hunter, Lyle J. Palmer, Ulf Gyllensten, Jianfeng Xu, Astrid Petersmann, Johan G. Eriksson, Guillaume Lettre, Teresa Ferreira, Fredrik Wiklund, Andreas Ziegler, Andres Metspalu, Jerome I. Rotter, Suzanne Rafelt, Julius S. Ngwa, Francis S. Collins, Michael N. Weedon, Thomas Illig, Wolfgang Hoffman, Nancy L. Heard-Costa, Anke Tönjes, Daniel I. Chasman, Alice M. Arnold, Olli T. Raitakari, Anna L. Dixon, Lu Qi, Michael E. Goddard, Anneli Pouta, Mark J. Caulfield, Liesbeth Vandenput, Christian Gieger, L. Adrienne Cupples, Veikko Salomaa, Elizabeth L. Altmaier, Nicholas G. Martin, Thomas D. Kocher, Jubao Duan, David S. Siscovick, Heikki V. Huikuri, Willem H. Ouwehand, Kari E. North, Christian Hengstenberg, Jacques S. Beckmann, Constance Chen, John Perry, Ana Marušić, Olle Melander, John D. Rioux, Erika Salvi, Andrew T. Hattersley, Paul Elliott, Leif Groop, Cristen J. Willer, Manuela Uda, Gudmar Thorleifsson, Eric E. Schadt, Charles C. White, Pablo V. Gejman, Serena Sanna, Ulla Sovio, Robert W. Lawrence, Unnur Thorsteinsdottir, Ayellet V. Segrè, Daniele Cusi, G. Bragi Walters, Ken Sin Lo, Ivana Kolcic, Igor Rudan, Sonja I. Berndt, Keri L. Monda, Soumya Raychaudhuri, Jian'an Luan, Joshua C. Randall, Anthony J. Balmforth, Yurii S. Aulchenko, Peter Almgren, Karen L. Mohlke, Timothy M. Frayling, Shamika Ketkar, Thomas H. Mosley, Markus Perola, Henry Völzke, Laura Zagato, Leena Peltonen, Seppo Koskinen, Massimo Mangino, Ke Hao, Tsegaselassie Workalemahu, Lambertus A. Kiemeney, Helene Alavere, Jaakko Tuomilehto, Reedik Mägi, James F. Wilson, Ingrid B. Borecki, Zoltán Kutalik, Michael Stumvoll, Dominique J. Verlaan, Arthur W. Musk, Eero Kajantie, Jian Yang, Joshua W. Knowles, Tuomas O. Kilpeläinen, Michael Boehnke, G. Mark Lathrop, John Beilby, Fernando Rivadeneira, Gudny Eiriksdottir, Gonneke Willemsen, Andrew C. Heath, Antonella Mulas, Katja K.H. Aben, David P. Strachan, Thor Aspelund, Jing Hua Zhao, Psychiatry, NCA - Anxiety & Depression, EMGO - Mental health, Internal Medicine, Epidemiology, Intensive Care, Clinical Genetics, Genetic Identification, Medical Research Council (MRC), Biological Psychology, Neuroscience Campus Amsterdam - Anxiety & Depression, EMGO+ - Mental Health, Genetics of Complex Traits, University of Exeter, Department of Epidemiology, Erasmus Medical Centre, Netherlands Genomics Initiative (NGI), Netherlands Genomics Initiative, Department of Medicine, Montreal, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Department of Biostatistics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, deCODE Genetics, deCODE genetics [Reykjavik], Divisions of Genetics and Endocrinology and Program in Genomics, Boston Children's Hospital, Metabolism Initiative and Program in Medical and Population Genetics, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Institut de Génomique d'Evry (IG), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, the Genetic Investigation of ANthropocentric Traits (GIANT) Consortium, Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Netherlands Twin Register (NTR), Multifactorial Inheritance, [SDV]Life Sciences [q-bio], Genome-wide association study, Aetiology, screening and detection [ONCOL 5], 0302 clinical medicine, POPULATION, SNPS, Genetics, 0303 health sciences, Multidisciplinary, HERITABILITY, COMMON VARIANTS, Phenotype, DISEASES, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Science & Technology - Other Topics, GROWTH, Allelic heterogeneity, Chromosomes, Human, Pair 3, Metabolic Networks and Pathways, TRAITS, Common disease-common variant, General Science & Technology, Locus (genetics), Biology, Polymorphism, Single Nucleotide, Article, Molecular epidemiology [NCEBP 1], 03 medical and health sciences, SDG 3 - Good Health and Well-being, ADULT, STRATIFICATION, MD Multidisciplinary, Humans, Genetic Predisposition to Disease, Genetic variability, 030304 developmental biology, Science & Technology, MULTIDISCIPLINARY SCIENCES, Genome, Human, Hormonal regulation [IGMD 6], Body Height, Genetic architecture, wide association analysis common variants heritability population adult stratification diseases traits growth snps, WIDE ASSOCIATION ANALYSIS, Genetic Loci, Evaluation of complex medical interventions [NCEBP 2], Polygene, Expression quantitative trait loci, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits1, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait2,3. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways ( P=0.016) and that underlie skeletal growth defects ( P
Published: 2010

14. Common variants in KCNN3 are associated with lone atrial fibrillation

Author: Gerhard Steinbeck, John Barnard, Dan M. Roden, Tamara B. Harris, Calum A. MacRae, Moritz F. Sinner, David R. Van Wagoner, Lenore J. Launer, Seiko Makino, Eric J. Topol, Siegfried Perz, Thomas J. Wang, Aravinda Chakravarti, Ke Wang, Kathryn L. Lunetta, Markus M. Nöthen, Mina K. Chung, Elsayed Z. Soliman, Stefan Kääb, David J. Milan, Mari Nelis, Stanley L. Hazen, Arne Pfeufer, Thomas Meitinger, Daniel Levy, Dawood Darbar, Susanne Moebus, Andres Metspalu, Jacqueline C.M. Witteman, Vilmundur Gudnason, Jonathan D. Smith, Albert Hofman, Anna Köttgen, Susan R. Heckbert, Paul I.W. de Bakker, Emelia J. Benjamin, Kenneth Rice, Britt-M. Beckmann, Ramachandran S. Vasan, Charlotte van Noord, Eric Boerwinkle, Stefan Möhlenkamp, Martina Mueller, Bruce M. Psaty, Alvaro Alonso, Dan E. Arking, H.-Erich Wichmann, Christopher Newton-Cheh, Man Li, Nicole L. Glazer, André G. Uitterlinden, Georg Ehret, Tõnu Esko, Bruno H. Stricker, Nicholas L. Smith, W. H. Linda Kao, Albert V. Smith, Steven A. Lubitz, Jerome I. Rotter, Patrick T. Ellinor, Renate B. Schnabel, Ervin R. Fox, Epidemiology, and Internal Medicine
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Heart disease, Small-Conductance Calcium-Activated Potassium Channels, Medizin, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, Article, Cohort Studies, Young Adult, Meta-Analysis as Topic, Polymorphism (computer science), Internal medicine, Atrial Fibrillation, Genetics, medicine, Humans, Aged, Genetic association, Case-control study, Atrial fibrillation, Odds ratio, Middle Aged, medicine.disease, Introns, Endocrinology, Case-Control Studies, Cardiology, Female, Genome-Wide Association Study, Cohort study
Abstract: Atrial fibrillation (AF) is the most common sustained arrhythmia. Previous studies have identified several genetic loci associated with typical AF. We sought to identify common genetic variants underlying lone AF. This condition affects a subset of individuals without overt heart disease and with an increased heritability of AF. We report a meta-analysis of genome-wide association studies conducted using 1,335 individuals with lone AF (cases) and 12,844 unaffected individuals (referents). Cases were obtained from the German AF Network, Heart and Vascular Health Study, the Atherosclerosis Risk in Communities Study, the Cleveland Clinic and Massachusetts General Hospital. We identified an association on chromosome 1q21 to lone AF (rs13376333, adjusted odds ratio = 1.56; P = 6.3 x 10(-12)), and we replicated this association in two independent cohorts with lone AF (overall combined odds ratio = 1.52, 95% CI 1.40-1.64; P = 1.83 x 10(-21)). rs13376333 is intronic to KCNN3, which encodes a potassium channel protein involved in atrial repolarization.
Published: 2010

15. A Genome-wide Association Study of Lung Cancer Identifies a Region of Chromosome 5p15 Associated with Risk for Adenocarcinoma

Author: James McKay, Neil E. Caporaso, Jarmo Virtamo, Lars J. Vatten, Heike Bickeböller, Egil Arnesen, Christine Bouchard, Sharon A. Savage, Dario Consonni, Rayjean J. Hung, Yufei Wang, Simone Benhamou, Ryan Diver, Angela Cecilia Pesatori, John R. McLaughlin, Demetrius Albanes, Hans E. Krokan, Melissa Rotunno, Andrew W. Bergen, Stephen J. Chanock, Kari Stefansson, Qizhai Li, Elizabeth W. Pugh, Meredith Yeager, H.-Erich Wichmann, Kai Yu, Michael J. Thun, Alisa M. Goldstein, Patrick Sulem, Laurie Burdette, Albert Rosenberger, Thorunn Rafnar, Sholom Wacholder, Mari Nelis, Tõnu Vooder, Kevin B. Jacobs, Gudmar Thorleifsson, Christopher I. Amos, Richard S. Houlston, Angela Risch, Joseph F. Fraumeni, Valerie Gaborieau, Timothy Eisen, Wiebke Sauter, Ming-Sound Tsao, Paul Brennan, Lynn R. Goldin, Zhaoming Wang, Cathy C. Laurie, Gary E. Goodman, Kimberly F. Doheny, Margaret A. Tucker, Kristian Välk, Jenny Chang-Claude, Frank Skorpen, John K. Field, Chu Chen, Margaret R. Spitz, Ying Wang, Lisa Mirabello, Martin M. Oken, Maria Teresa Landi, Nilanjan Chatterjee, Pier Alberto Bertazzi, William Wheeler, Andres Metsapalu, and Mark Lathrop
Subjects: Oncology, medicine.medical_specialty, Lung Neoplasms, Genotype, Population, Genome-wide association study, Adenocarcinoma, Biology, Polymorphism, Single Nucleotide, Linkage Disequilibrium, White People, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Meta-Analysis as Topic, Risk Factors, Report, Internal medicine, Odds Ratio, Genetics, medicine, Humans, Genetics(clinical), Genetic Predisposition to Disease, education, Lung cancer, Genetics (clinical), 030304 developmental biology, 0303 health sciences, education.field_of_study, Case-control study, Chromosome, Genetic Variation, Cancer, Odds ratio, medicine.disease, Lung cancer susceptibility, Human genetics, 3. Good health, Case-Control Studies, 030220 oncology & carcinogenesis, Chromosomes, Human, Pair 5, Erratum, Genome-Wide Association Study
Abstract: Three genetic loci for lung cancer risk have been identified by genome-wide association studies (GWAS), but inherited susceptibility to specific histologic types of lung cancer is not well established. We conducted a GWAS of lung cancer and its major histologic types, genotyping 515,922 single-nucleotide polymorphisms (SNPs) in 5739 lung cancer cases and 5848 controls from one population-based case-control study and three cohort studies. Results were combined with summary data from ten additional studies, for a total of 13,300 cases and 19,666 controls of European descent. Four studies also provided histology data for replication, resulting in 3333 adenocarcinomas (AD), 2589 squamous cell carcinomas (SQ), and 1418 small cell carcinomas (SC). In analyses by histology, rs2736100 (TERT), on chromosome 5p15.33, was associated with risk of adenocarcinoma (odds ratio [OR] = 1.23, 95% confidence interval [CI] = 1.13–1.33, p = 3.02 × 10−7), but not with other histologic types (OR = 1.01, p = 0.84 and OR = 1.00, p = 0.93 for SQ and SC, respectively). This finding was confirmed in each replication study and overall meta-analysis (OR = 1.24, 95% CI = 1.17–1.31, p = 3.74 × 10−14 for AD; OR = 0.99, p = 0.69 and OR = 0.97, p = 0.48 for SQ and SC, respectively). Other previously reported association signals on 15q25 and 6p21 were also refined, but no additional loci reached genome-wide significance. In conclusion, a lung cancer GWAS identified a distinct hereditary contribution to adenocarcinoma.
Published: 2009

16. Alcohol-related cancers and genetic susceptibility in Europe: the ARCAGE project: study samples and data collection

Author: Kristina Kjærheim, Patricia A. McKinney, Simone Benhamou, Franco Merletti, Antonio Agudo, Cristina Canova, Alena Slamova, B. E. McCartan, Xavier Castellsagué, Gary J. Macfarlane, Renato Talamini, Paul Brennan, Miriam Schejbalova, Pagona Lagiou, Lorenzo Richiardi, Ray Lowry, Christina Georgila, Andres Metspalu, Luigi Barzan, Lorenzo Simonato, Wolfgang Ahrens, Hermann Pohlabeln, Mari Nelis, P. Minaki, David I. Conway, Claire M. Healy, Tatiana V. Macfarlane, Manuela Marron, Mia Hashibe, Christine Bouchardy, and Ariana Znaor
Subjects: Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Pathology, Alcohol Drinking, Epidemiology, Single-nucleotide polymorphism, Head and Neck Neoplasms/etiology/genetics, Internal medicine, Genetic variation, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, Esophagus, Life Style, ddc:613, Aged, Aged, 80 and over, business.industry, Data Collection, Pharynx, Public Health, Environmental and Occupational Health, Case-control study, Cancer, upper aerodigestive cancers, case-control study, Middle Aged, Esophageal cancer, Alcohol Drinking/adverse effects/genetics, medicine.disease, Europe, stomatognathic diseases, medicine.anatomical_structure, Head and Neck Neoplasms, Case-Control Studies, Carcinoma, Squamous Cell/etiology/genetics, Carcinoma, Squamous Cell, Female, business
Abstract: Cancers of the upper aerodigestive tract (UADT) include those of the oral cavity, pharynx (other than nasopharynx), larynx, and esophagus. Tobacco smoking and consumption of alcoholic beverages are established causes of UADT cancers, whereas reduced intake of vegetables and fruits are likely causes. The role of genetic predisposition and possible interactions of genetic with exogenous factors, however, have not been adequately studied. Moreover, the role of pattern of smoking and drinking, as well as the exact nature of the implicated dietary variables, has not been clarified. To address these issues, the International Agency for Research on Cancer initiated in 2002 the alcohol-related cancers and genetic susceptibility (ARCAGE) in Europe project, with the participation of 15 centers in 11 European countries. Information and biological data from a total of 2304 cases and 2227 controls have been collected and will be used in a series of analyses. A total of 166 single nucleotide polymorphisms of 76 genes are being studied for genetic associations with UADT cancers. We report here the methodology of the ARCAGE project, main demographic and lifestyle characteristics of the cases and controls, as well as the distribution of cases by histology and subsite. About 80% of cases were males and fewer than 20% of all cases occurred before the age of 50 years. Overall, the most common subsite was larynx, followed by oral cavity, oropharynx, esophagus and hypopharynx. Close to 90% of UADT cancers were squamous cell carcinomas. A clear preponderance of smokers and alcohol drinkers among UADT cases compared with controls was observed.
Published: 2009

17. Identification of lung cancer histology-specific variants applying Bayesian framework variant prioritization approaches within the TRICL and ILCCO consortia

Author: Keitaro Matsuo, Neil E. Caporaso, John R. Gosney, Juncheng Dai, Maiken Elvestad Gabrielsen, Margaret R. Spitz, Frank Skorpen, Tõnu Vooder, Neonila Szeszenia-Dabrowska, Paul Brennan, Brian E. Henderson, Shelley S. Tworoger, Vladimir Bencko, Xuchen Zong, Younghun Han, Olaide Y. Raji, Yufei Wang, Andres Metspalu, Hidemi Ito, Irene Orlow, Michael W. Marcus, Eleonora Fabianova, Chu Chen, James McKay, Ping Yang, Gary E. Goodman, Hans E. Krokan, Demetrius Albanes, Timothy Eisen, Geoffrey Liu, Ying Chen, Triantafillos Liloglou, Jolanta Lissowska, Lynne R. Wilkens, Mari Nelis, Mark Lathrop, John K. Field, Fumihiko Matsuda, Di Zhang, Yongyue Wei, Dana Mates, Peter Rudnai, Yonathan Brhane, Jun She, Victoria L. Stevens, Inger Njølstad, Hongbing Shen, Darren R. Brenner, Maria Teresa Landi, Susan M. Gapstur, Li Su, Michael P.A. Davies, David Zaridze, Loic Le Marchand, John R. McLaughlin, Dong Xie, Paolo Boffetta, Rayjean J. Hung, Peter Broderick, Albert Rosenberger, Hendrik Dienemann, Lenka Foretova, Thomas Muley, Christopher I. Amos, Vladimi Janout, David C. Christiani, Joachim Heinrich, Yafang Li, Lars J. Vatten, Mattias Johansson, Richard S. Houlston, Xifeng Wu, Kristjan Välk, Wei V. Chen, Heike Bickeböller, Angela Risch, Maria Timofeeva, Brenner, D.R., Amos, C.I., Brhane, Y., Timofeeva, M.N., Caporaso, N., Wang, Y., Christiani, D.C., Bickeböller, H., Yang, P., Albanes, D., Stevens, V.L., Gapstur, S., McKay, J., Boffetta, P., Zaridze, D., Szeszenia-Dabrowska, N., Lissowska, J., Rudnai, P., Fabianova, E., Mates, D., Bencko, V., Foretova, L., Janout, V., Krokan, H.E., Skorpen, F., Gabrielsen, M.E., Vatten, L., Njølstad, I., Chen, C., Goodman, G., Lathrop, M., Vooder, T., Välk, K., Nelis, M., Metspalu, A., Broderick, P., Eisen, T., Wu, X., Zhang, D., Chen, W., Spitz, M.R., Wei, Y., Su, L., Xie, D., She, J., Matsuo, K., Matsuda, F., Ito, H., Risch, A., Heinrich, J., Rosenberger, A., Muley, T., Dienemann, H., Field, J.K., Raji, O., Chen, Y., Gosney, J., Liloglou, T., Davies, M.P.A., Marcus, M., McLaughlin, J., Orlow, I., Han, Y., Li, Y., Zong, X., Johansson, M., Liu, G., Tworoger, S.S., Le Marchand, L., Henderson, B.E., Wilkens, L.R., Dai, J., Shen, H., Houlston, R.S., Landi, M.T., Brennan, P., and Hung, R.J.
Subjects: Cancer Research, Lung Neoplasms, Bayesian probability, Genome-wide association study, Original Manuscript, Computational biology, Adenocarcinoma, Bioinformatics, 03 medical and health sciences, Bayes' theorem, 0302 clinical medicine, medicine, Humans, Genetic Predisposition to Disease, Lung cancer, 030304 developmental biology, Genetic association, 0303 health sciences, business.industry, Case-control study, Bayes Theorem, General Medicine, medicine.disease, 3. Good health, ComputingMethodologies_PATTERNRECOGNITION, 030220 oncology & carcinogenesis, Meta-analysis, Case-Control Studies, Carcinoma, Squamous Cell, business, Genome-Wide Association Study
Abstract: Large-scale genome-wide association studies (GWAS) have likely uncovered all common variants at the GWAS significance level. Additional variants within the suggestive range (0.0001> P > 5×10(-8)) are, however, still of interest for identifying causal associations. This analysis aimed to apply novel variant prioritization approaches to identify additional lung cancer variants that may not reach the GWAS level. Effects were combined across studies with a total of 33456 controls and 6756 adenocarcinoma (AC; 13 studies), 5061 squamous cell carcinoma (SCC; 12 studies) and 2216 small cell lung cancer cases (9 studies). Based on prior information such as variant physical properties and functional significance, we applied stratified false discovery rates, hierarchical modeling and Bayesian false discovery probabilities for variant prioritization. We conducted a fine mapping analysis as validation of our methods by examining top-ranking novel variants in six independent populations with a total of 3128 cases and 2966 controls. Three novel loci in the suggestive range were identified based on our Bayesian framework analyses: KCNIP4 at 4p15.2 (rs6448050, P = 4.6×10(-7)) and MTMR2 at 11q21 (rs10501831, P = 3.1×10(-6)) with SCC, as well as GAREM at 18q12.1 (rs11662168, P = 3.4×10(-7)) with AC. Use of our prioritization methods validated two of the top three loci associated with SCC (P = 1.05×10(-4) for KCNIP4, represented by rs9799795) and AC (P = 2.16×10(-4) for GAREM, represented by rs3786309) in the independent fine mapping populations. This study highlights the utility of using prior functional data for sequence variants in prioritization analyses to search for robust signals in the suggestive range.
Published: 2015

18. Erratum: Corrigendum: Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer

Author: Mari Nelis, Neil E. Caporaso, Tõnu Vooder, H. Bas Bueno-de-Mesquita, Ben Kinnersley, Frank Skorpen, Stephen J. Chanock, Mattias Johansson, Gary E. Goodman, Athena Matakidou, Kay-Tee Khaw, Amy Lloyd, Dana Mates, Neonilia Szeszenia-Dabrowska, Elisabete Weiderpass, Maiken Elvestad Gabrielsen, Paul Brennan, David C. Christiani, Maria Teresa Landi, Susan M. Gapstur, Yuanqing Ye, Andres Metspalu, Hendrik Dienemann, Nilanjan Chatterjee, Margaret R. Spitz, Younghun Han, Christopher I. Amos, James McKay, Manon Delahaye-Sourdeix, Lars J. Vatten, William Wheeler, Eleonora Fabianova, Daniel Chubb, Simone Benhamou, T. Eisen, Peter Rudnai, Chu Chen, Ghislaine Scelo, Antonio Agudo, Paolo Vineis, Marcin Lener, Mikael Johansson, Angela Risch, Maria Timofeeva, Mark Lathrop, Li Su, Yongyue Wei, Victoria L. Stevens, Peter Broderick, Maxime Vallée, Inger Njølstad, Rayjean J. Hung, David Zaridze, Thorunn Rafnar, Vladimir Janout, Yufei Wang, Jian Gu, Hans E. Krokan, Marc Henrion, Lenka Foretova, Kari Stefansson, Gudmar Thorleifsson, Demetrius Albanes, Patrick Sulem, Geoffrey Liu, Rudolf Kaaks, Marina Laplana, Jan Lubinski, Xuchen Zong, Vladimir Bencko, Elio Riboli, Zhaoming Wang, Françoise Clavel-Chapelon, Albert Rosenberger, Dimitrios Trichopoulos, Valerie Gaborieau, Florence Le Calvez-Kelm, Anne Tjønneland, Wei V. Chen, Jolanta Lissowska, Kristjan Välk, Richard S. Houlston, and Xifeng Wu
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Biology, Affect (psychology), medicine.disease, 3. Good health, 03 medical and health sciences, 030104 developmental biology, Internal medicine, Genetics, medicine, Lung cancer, CHEK2
Abstract: Nat. Genet. 46, 736–741 (2014); published online 1 June 2014; corrected after print 23 January 2017 In the version of this article initially published, the name of author Florence Le Calvez-Kelm appeared incorrectly as Florence LeCalvez-Kelm. The error has been corrected in the HTML and PDF versionsof the article.
Published: 2017

19. Hearing impairment in Estonia: an algorithm to investigate genetic causes in pediatric patients

Author: Katrin Kruustük, Olga Zilina, L Tranebjaerg, Rita Teek, Tiia Reimand, Riina Žordania, Kairit Joost, Neeme Tõnisson, Katrin Õunap, Tiina Kahre, and Mari Nelis
Subjects: Proband, Estonia, Male, Adolescent, Hearing loss, Hearing Loss, Sensorineural, Anion Transport Proteins, Connexins, Connexin 30, Medicine, Humans, Clinical significance, Allele, Age of Onset, Child, biology, business.industry, Hearing Tests, Infant, Newborn, Infant, Membrane Transport Proteins, General Medicine, medicine.disease, Connexin 26, RNA, Ribosomal, Sulfate Transporters, Child, Preschool, Cytomegalovirus Infections, biology.protein, Etiology, Sensorineural hearing loss, Female, Age of onset, medicine.symptom, business, Algorithm, GJB6, Algorithms
Abstract: Purpose The present study was initiated to establish the etiological causes of early onset hearing loss (HL) among Estonian children between 2000–2009. Methods The study group consisted of 233 probands who were first tested with an arrayed primer extension assay, which covers 199 mutations in 7 genes ( GJB2, GJB6, GJB3, SLC26A4, SLC26A5 genes, and two mitochondrial genes – 12S rRNA, tRNA Ser(UCN) ). From probands whose etiology of HL remained unknown, DNA analysis of congenital cytomegalovirus (CMV) infection and G-banded karyotype and/or chromosomal microarray analysis (CMA) were performed. Results In 110 (47%) cases, the etiology of HL was genetic and in 5 (2%) congenital CMV infection was diagnosed. We found mutations with clinical significance in GJB2 (100 children, 43%) and in 2 mitochondrial genes (2 patients, 1%). A single mutation in SLC26A4 gene was detected in 5 probands (2.2%) and was considered diagnostic. In 4 probands a heterozygous IVS2-2A>G change in the SLC26A5 gene was found. We did not find any instances of homozygosity for this splice variant in the probands. CMA identified in 4 probands chromosomal regions with the loss of one allele. In 2 of them we were able to conclude that the found abnormalities are definitely pathogenic (12q13.3-q14.2 and 17q22-23.2 microdeletion), but the pathogenity of 2 other findings (3p26.2 and 1p33 microdeletion) remained unknown. Conclusion This practical diagnostic algorithm confirmed the etiology of early onset HL for 115 Estonian patients (49%). This algorithm may be generalized to other populations for clinical application.
Published: 2013

20. Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer

Author: Paul Brennan, Younghun Han, Vladimir Janout, Eleonora Fabianova, Mark Lathrop, Zhaoming Wang, Inger Njølstad, James McKay, Dana Mates, Jolanta Lissowska, Frank Skorpen, Chu Chen, Neonilia Szeszenia-Dabrowska, Françoise Clavel-Chapelon, Antonio Agudo, Mattias Johansson, David C. Christiani, Kay-Tee Khaw, Yongyue Wei, Thorunn Rafnar, Gary E. Goodman, Mikael Johansson, Daniel Chubb, Xuchen Zong, Simone Benhamou, Vladimir Bencko, Manon Delahaye-Sourdeix, Lars J. Vatten, Elio Riboli, Peter Rudnai, Maria Teresa Landi, Susan M. Gapstur, Yuanqing Ye, Nilanjan Chatterjee, Amy Lloyd, Margaret R. Spitz, Paolo Vineis, H. Bas Bueno-de-Mesquita, William Wheeler, Ghislaine Scelo, Jan Lubinski, Stephen J. Chanock, Valerie Gaborieau, Victoria L. Stevens, Marc Henrion, Kari Stefansson, David Zaridze, Peter Broderick, Jian Gu, Mari Nelis, Elisabete Weiderpass, Albert Rosenberger, Maiken Elvestad Gabrielsen, Dimitrios Trichopoulos, Kristjan Välk, Florence LeCalvez-Kelm, Tõnu Vooder, Ben Kinnersley, Richard S. Houlston, Xifeng Wu, Anne Tjønneland, Yufei Wang, Hans E. Krokan, Demetrius Albanes, Patrick Sulem, Neil E. Caporaso, Geoffrey Liu, Marina Laplana, Christopher I. Amos, T. Eisen, Li Su, Lenka Foretova, Gudmar Thorleifsson, Rayjean J. Hung, Andres Metspalu, Maxime Vallée, Athena Matakidou, Hendrik Dienemann, Rudolf Kaaks, Marcin Lener, Angela Risch, Maria Timofeeva, and Wei V. Chen
Subjects: Lung Neoplasms, Genome-wide association study, Biology, Adenocarcinoma, Bioinformatics, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, 0302 clinical medicine, Meta-Analysis as Topic, Risk Factors, Genetics, medicine, Humans, Genetic Predisposition to Disease, 1000 Genomes Project, Lung cancer, CHEK2, 030304 developmental biology, BRCA2 Protein, 0303 health sciences, 9. Industry and infrastructure, Case-control study, Odds ratio, medicine.disease, Prognosis, 3. Good health, Checkpoint Kinase 2, 030220 oncology & carcinogenesis, Case-Control Studies, Carcinoma, Squamous Cell, Imputation (genetics), Genome-Wide Association Study
Abstract: We conducted imputation to the 1000 Genomes Project of four genome-wide association studies of lung cancer in populations of European ancestry (11,348 cases and 15,861 controls) and genotyped an additional 10,246 cases and 38,295 controls for follow-up. We identified large-effect genome-wide associations for squamous lung cancer with the rare variants BRCA2 p.Lys3326X (rs11571833, odds ratio (OR) = 2.47, P = 4.74 × 10−20) and CHEK2 p.Ile157Thr (rs17879961, OR = 0.38, P = 1.27 × 10−13). We also showed an association between common variation at 3q28 (TP63, rs13314271, OR = 1.13, P = 7.22 × 10−10) and lung adenocarcinoma that had been previously reported only in Asians. These findings provide further evidence for inherited genetic susceptibility to lung cancer and its biological basis. Additionally, our analysis demonstrates that imputation can identify rare disease-causing variants with substantive effects on cancer risk from preexisting genome-wide association study data. We acknowledge The Cancer Genome Atlas (TCGA) for their contribution of lung cancer genomic data to this study (TCGA Project Number 3230). We also acknowledge support from the National Institute for Health Research Biomedical Research Centre at the Royal Marsden Hospital. This study was supported by the NIH (U19CA148127, R01CA055769, 5R01CA127219, 5R01CA133996 and 5R01CA121197). The work performed at ICR was supported by Cancer Research UK (C1298/A8780 and C1298/A8362), National Cancer Research Network (NCRN), HEAL, Sanofi-Aventis and National Health Service funding to the Royal Marsden Hospital and Institute of Cancer Research, as well as the National Institute for Health Research Biomedical Research Centre. B.K. was the recipient of a Sir John Fisher Foundation PhD studentship. Work at ICR was also supported by NIH GM103534 and the Institute for Quantitative Biomedical Sciences at Dartmouth to C.I.A. The work performed in Toronto was supported by The Canadian Cancer Society Research Institute (020214), Ontario Institute of Cancer and Cancer Care Ontario Chair Award to R.J.H. and G.L. and the Alan Brown Chair and Lusi Wong Programs at the Princess Margaret Hospital Foundation. The work performed at Heidelberg was supported by Deutsche Krebshilfe (70-2387 and 70-2919) and the German Federal Ministry of Education and Research (EPIC-Heidelberg). The work performed at IARC was supported by the Institut National du Cancer, France, the European Community (LSHG-CT-2005-512113), the Norwegian Cancer Association, the Functional Genomics Programme of Research Council of Norway, the European Regional Development Fund and the State Budget of the Czech Republic (RECAMO, CZ.1.05/2.1.00/03.0101), the NIH (R01-CA111703 and UO1-CA63673), the Fred Hutchinson Cancer Research Center, the US NCI (R01 CA092039), an FP7 grant (REGPOT 245536), the Estonian Government (SF0180142s08), the EU European Regional Development Fund in the frame of Centre of Excellence in Genomics and Estonian Research Infrastructure's Roadmap and the University of Tartu (SP1GVARENG) and an IARC Postdoctoral Fellowship (M.N.T.). Work at the NCI was supported by the Intramural Research Program of the NIH, the NCI, US Public Health Service contracts NCI (N01-CN-45165, N01-RC-45035, N01-RC-37004, NO1-CN-25514, NO1-CN-25515, NO1-CN-25512, NO1-CN-25513, NO1-CN-25516, NO1-CN-25511, NO1-CN-25524, NO1-CN-25518, NO1-CN-75022, NO1-CN-25476 and NO1-CN-25404), the American Cancer Society, the NIH Genes, Environment and Health Initiative in part by HG-06-033-NCI-01 and RO1HL091172-01, genotyping at the Johns Hopkins University Center for Inherited Disease Research (U01HG004438 and NIH HHSN268200782096C) and study coordination at the GENEVA Coordination Center (U01 HG004446). Work was also supported by NIH grants (P50 CA70907, R01CA121197, RO1 CA127219, U19 CA148127 and RO1 CA55769) and a Cancer Prevention Research Institute of Texas grant (RP100443). Genotyping was provided by the Center for Inherited Disease Research (CIDR). Work performed at Harvard was supported by the NIH (CA074386, CA092824 and CA090578). The Icelandic study was supported in part by NIH DA17932.
Published: 2013

21. Genome-wide analysis of BMI in adolescents and young adults reveals additional insight into the effects of genetic loci over the life course

Author: Keri L. Monda, Caroline S. Fox, David P. Strachan, Henri Wallaschofski, M. Carola Zillikens, Andres Metspalu, Tit Nikopensius, Sabine Schipf, Zhaoming Wang, Cornelia M. van Duijn, Richard B. Hayes, Audrey C. Choh, Mariaelisa Graff, Henry Völzke, Xiangjun Xiao, Cucca Francesco, Ellen W. Demerath, Carlo Sidore, Mary L. Marazita, Julius S. Ngwa, John R. Shaffer, Richard J. Crout, Penny Gordon-Larsen, Rob M. van Dam, Ben A. Oostra, Tsegaselassie Workalemahu, David Schlessinger, Lakatta Edward, Stefan A. Czerwinski, L. Adrienne Cupples, Thomas D. Dyer, Larry D. Atwood, Najaf Amin, Paul Scheet, Georg Homuth, Bradford Towne, Charles S. White, Frank B. Hu, Sonja I. Berndt, Stephen J. Chanock, Gonçalo R. Abecasis, Kari E. North, Nancy L. Heard-Costa, Lu Qi, Alexander Teumer, Serena Sanna, Mari Nelis, Tõnu Esko, Kevin B. Jacobs, Epidemiology, Clinical Genetics, and Internal Medicine
Subjects: Adult, Adolescent, 030209 endocrinology & metabolism, Locus (genetics), Genome-wide association study, Single-nucleotide polymorphism, Biology, Weight Gain, Polymorphism, Single Nucleotide, White People, Body Mass Index, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Genetic variation, Genetics, medicine, Humans, Young adult, 10. No inequality, Molecular Biology, Genetics (clinical), 030304 developmental biology, Genetic association, Aged, Aged, 80 and over, 0303 health sciences, Association Studies Articles, Age Factors, General Medicine, Middle Aged, medicine.disease, Obesity, Genetic Loci, Body mass index, Demography, Genome-Wide Association Study
Abstract: Genetic loci for body mass index (BMI) in adolescence and young adulthood, a period of high risk for weight gain, are understudied, yet may yield important insight into the etiology of obesity and early intervention. To identify novel genetic loci and examine the influence of known loci on BMI during this critical time period in late adolescence and early adulthood, we performed a two-stage meta-analysis using 14 genome-wide association studies in populations of European ancestry with data on BMI between ages 16 and 25 in up to 29 880 individuals. We identified seven independent loci (P < 5.0 × 10⁻⁸) near FTO (P = 3.72 × 10⁻²³), TMEM18 (P = 3.24 × 10⁻¹⁷), MC4R (P = 4.41 × 10⁻¹⁷), TNNI3K (P = 4.32 × 10⁻¹¹), SEC16B (P = 6.24 × 10⁻⁹), GNPDA2 (P = 1.11 × 10⁻⁸) and POMC (P = 4.94 × 10⁻⁸) as well as a potential secondary signal at the POMC locus (rs2118404, P = 2.4 × 10⁻⁵ after conditioning on the established single-nucleotide polymorphism at this locus) in adolescents and young adults. To evaluate the impact of the established genetic loci on BMI at these young ages, we examined differences between the effect sizes of 32 published BMI loci in European adult populations (aged 18-90) and those observed in our adolescent and young adult meta-analysis. Four loci (near PRKD1, TNNI3K, SEC16B and CADM2) had larger effects and one locus (near SH2B1) had a smaller effect on BMI during adolescence and young adulthood compared with older adults (P < 0.05). These results suggest that genetic loci for BMI can vary in their effects across the life course, underlying the importance of evaluating BMI at different ages.
Published: 2013

22. A common biological basis of obesity and nicotine addiction

Author: Peter Kovacs, Angela Döring, Frank Geller, Lenka Foretova, Dana Mates, Paul M. Ridker, Francesco Mauri, Mark J. Caulfield, Nora Franceschini, Neonilia Szeszenia-Dabrowska, Toshiko Tanaka, Pagona Lagiou, Jennifer E. Huffman, Paul Scheet, Gudmar Thorleifsson, Jacqueline M. Vink, Nicole Vogelzangs, Ida Surakka, Jeffrey R. Gulcher, Ulrich John, Veikko Salomaa, Eco J. C. de Geus, Hakon Hakonarson, Anne Barton, Luigi Barzan, H.-Erich Wichmann, Anneli Pouta, Peter Vollenweider, Kristina Kjærheim, Jed E. Rose, Ruth J. F. Loos, Susanne Lucae, Danielle Posthuma, Henning Tiemeier, Fangyi Gu, Mark I. McCarthy, Unnur Styrkarsdottir, James McKay, Talin Haritunians, Martin Preisig, Olle Melander, Xavier Castellsagué, William H. Matthai, Piera Angelica Merlini, Daniel I. Chasman, Michael Stumvoll, Ozren Polasek, Nilesh J. Samani, Søren Besenbacher, Jane Worthington, Daniel F. Gudbjartsson, Alistair S. Hall, Antonio Agudo, Keith Matthews, Gonçalo R. Abecasis, Jaana Laitinen, Norbert Dahmen, Robert W. Mahley, Mari Nelis, Inga Prokopenko, Anke Tönjes, Iris H Gudjonsdottir, Joshua W. Knowles, Jing Hua Zhao, Jouke-Jan Hottenga, Vincent Mooser, Jack Satsangi, Cristina Canova, Stephen P. Fortmann, Hreinn Stefansson, Manuela Uda, T. Brueckl, Mary Susan Burnett, Michael Boehnke, Veronique Vitart, Philip J. Barter, Ruth McPherson, Benjamin F. Voight, Patrick F. Sullivan, Pier Mannuccio Mannucci, Michael Wittig, Kari Stefansson, Lowell F. Satler, Eric Boerwinkle, Benjamin J. Wright, Ben A. Oostra, John Strauss, Stefania Bandinelli, S. Horstmann, Jonathan Marchini, Simone Benhamou, Stephen E. Epstein, Rajesh Rawal, Vladimir Janout, Miles Parkes, Liming Qu, Yuri Milaneschi, Peter Almgren, Kaisu Keskitalo, Matti Isohanni, Dan Rujescu, John P. A. Ioannidis, Peter Rudnai, Stefan Walter, Diego Ardissino, John B. Vincent, Leif Groop, Kent D. Taylor, Christopher J. O'Donnell, Christopher W. Knouff, David I. Conway, Thomas Quertermous, Joseph M. Lindsay, Stephen M. Schwartz, Tariq Ahmed, Jolanta Lissowska, Evan L. Thacker, Igor Rudan, Sreekumar G. Pillai, Janet Audrain-McGovern, Daniel Levy, S. Kathiresan, Timothy M. Frayling, Brenda W.J.H. Penninx, Shen Huei-Yi, Johannes H. Smit, Gonneke Willemsen, Henry Völzke, John R. B. Perry, Federica Tozzi, Roberto Elosua, Devin Absher, G B Walters, Augusto D. Pichard, Stephen J. Chanock, Katja K.H. Aben, Anna-Liisa Hartikainen, Maria Krestyaninova, Ivana Holcatova, Tim D. Spector, Ming D. Li, Xiangjun Xiao, Barbara McKnight, Hans J. Grabe, Martin den Heijer, Caroline Hayward, Unnur Thorsteinsdottir, Douglas F. Levinson, Claes Ladenvall, Robert L. Wilensky, Danyu Lin, Nicole Soranzo, Lefkos T. Middleton, Jason S. Liu, Wade H. Berrettini, Laura M. Thornton, Muredach P. Reilly, Jack M. Guralnik, Ron Waksman, Per Bakke, Alan F. Wright, Andre Franke, Thorgeir E. Thorgeirsson, Barbara Nitz, Anthony J. Balmforth, Jaspal S. Kooner, Gavin Lucas, Esther H. Lips, Helena Furberg, Albert Hofman, Patrick Sulem, Astrid Petersmann, Ivana Kolcic, Jaakko Tuomilehto, Lorenzo Richiardi, Pablo V. Gejman, Claire J. Steves, Thorarinn Tyrfingsson, Yurii S. Aulchenko, Brendan M. Everett, Ariana Znaor, Maxine Allen, Thorunn Rafnar, Mark Lathrop, Reedik Mägi, Kenneth M. Kent, M. Perola, Nicholas J. Wareham, Daniel J. Rader, John R. Thompson, Sarah R. Preis, Peter Kraft, Caryn Lerman, Hogni Oskarsson, Alan R. Sanders, Alexander Teumer, Xin Yuan, Cornelia M. van Duijn, Samuli Ripatti, André G. Uitterlinden, Carl A. Anderson, Martin Farrall, Kay-Tee Khaw, Joachim Heinrich, Heather M. Stringham, Bruce M. Psaty, Jaakko Kaprio, Valgerdur Steinthorsdottir, Steve Eyre, James F. Wilson, David J. Hunter, Johannes Kettunen, Wendy Thomson, Antero Kesäniemi, Karen L. Mohlke, Christian Gieger, Tatiana V. Macfarlane, Jubao Duan, Anne Farmer, Clyde Francks, Joshua C. Bis, Harry Campbell, Pierandrea Muglia, Andres Metspalu, Dawn M. Waterworth, Ramachandran S. Vasan, Hermine H. Maes, David Zaridze, Luisa Bernardinelli, Vladimir Bencko, Massimo Mangino, Lambertus A. Kiemeney, Solveig Gretarsdottir, Tõnu Esko, Anne U. Jackson, Claire M. Healy, Scott M. Grundy, David St Clair, Curt D. Furberg, Mingyao Li, Peter McGuffin, Christopher G. Mathew, David Altshuler, Dorret I. Boomsma, Susan Campbell, Jianxin Shi, Najaf Amin, James L. Kennedy, Ana M. Valdes, Anna F. Dominiczak, Themistocles L. Assimes, Susan E. Hankinson, Inês Barroso, Marjo-Riitta Järvelin, Guillaume Paré, Joe Devaney, Antonio Terracciano, David Schlessinger, Paul Brennan, Shih-Jen Hwang, Luigi Ferrucci, Ray Lowry, Jennifer Dackor, Eleonora Fabianova, Lina Zgaga, Emelia J. Benjamin, Fabio Busonero, Sarah H. Wild, Patricia B. Munroe, John C. Chambers, Carlos Iribarren, Marcus Ising, Yunjung Kim, Richard O. Day, Amund Gulsvik, Gérard Waeber, Claudia Lamina, Arne Schäfer, Functional Genomics, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, Hjelt Institute (-2014), Department of Public Health, Institute for Molecular Medicine Finland, Genetic Epidemiology, Human genetics, and NCA - Neurobiology of mental health
Subjects: obesity, FOOD-INTAKE, TAG Consortium, medicine.medical_treatment, Oxford-GSK Consortium, LOCI, Iceland, Aetiology, screening and detection [ONCOL 5], VARIANTS, 3124 Neurology and psychiatry, Nicotine, 0302 clinical medicine, DEPENDENCE, 030212 general & internal medicine, Age of Onset, ENGAGE consortium, POPULATION, Addiction, Body Mass Index, Nicotine dependence, Smoking, media_common, Psychiatry, 2. Zero hunger, 0303 health sciences, education.field_of_study, ASSOCIATION, Tobacco Use Disorder, DSM-V, CANCER, 3142 Public health care science, environmental and occupational health, 3. Good health, Psychiatry and Mental health, Meta-analysis, Original Article, addiction, Life Sciences & Biomedicine, medicine.drug, medicine.medical_specialty, media_common.quotation_subject, Population, body mass index, Polymorphism, Single Nucleotide, smoking, 03 medical and health sciences, Cellular and Molecular Neuroscience, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Humans, SMOKING-BEHAVIOR, nicotine dependence, education, Biological Psychiatry, Molecular epidemiology Aetiology, screening and detection [NCEBP 1], 030304 developmental biology, Science & Technology, business.industry, Appetite, medicine.disease, Obesity, BODY-MASS INDEX, Behavior, Addictive, Endocrinology, Smoking cessation, business, Body mass index
Abstract: Contains fulltext : 128630.pdf (Publisher’s version ) (Open Access) Smoking influences body weight such that smokers weigh less than non-smokers and smoking cessation often leads to weight increase. The relationship between body weight and smoking is partly explained by the effect of nicotine on appetite and metabolism. However, the brain reward system is involved in the control of the intake of both food and tobacco. We evaluated the effect of single-nucleotide polymorphisms (SNPs) affecting body mass index (BMI) on smoking behavior, and tested the 32 SNPs identified in a meta-analysis for association with two smoking phenotypes, smoking initiation (SI) and the number of cigarettes smoked per day (CPD) in an Icelandic sample (N=34,216 smokers). Combined according to their effect on BMI, the SNPs correlate with both SI (r=0.019, P=0.00054) and CPD (r=0.032, P=8.0 x 10(-7)). These findings replicate in a second large data set (N=127,274, thereof 76,242 smokers) for both SI (P=1.2 x 10(-5)) and CPD (P=9.3 x 10(-5)). Notably, the variant most strongly associated with BMI (rs1558902-A in FTO) did not associate with smoking behavior. The association with smoking behavior is not due to the effect of the SNPs on BMI. Our results strongly point to a common biological basis of the regulation of our appetite for tobacco and food, and thus the vulnerability to nicotine addiction and obesity.
Published: 2013

23. 412 Combination of Genomic Technologies and Consanguinity in Order to Identify Pathogenic Variants in Recessive Disorders

Author: A Vanier, Amira Masri, Emilie Falconnet, Nadine Jalkh, Stylianos E. Antonarakis, Armand Bottani, Hanan Hamamy, Fatma Al-Jasmi, G Duriaux-Sail, Mari Nelis, Siv Fokstuen, Elisavet Stathaki, S Al-Hait, Stefania Gimelli, Periklis Makrythanasis, Siham Chafai Elalaoui, Mona Aglan, Sophia Kitsiou, E. Kanavakis, Federico Santoni, Lihadh Al-Gazali, N All-Allawi, Michel Guipponi, H Frissyra, Abdelaziz Sefiani, Frédérique Béna, Samia A. Temtamy, Stavroula Psoni, André Mégarbané, H Chaabouni Bouhamed, and Maha S. Zaki
Subjects: Genetics, Candidate gene, Genotype-phenotype distinction, business.industry, Pediatrics, Perinatology and Child Health, Medicine, Consanguinity, Runs of Homozygosity, Allele, business, Genotyping, Inbreeding, Exome
Abstract: Consanguinity and inbreeding increase the sharing of alleles among individuals; thus a considerable number of autosomal recessive phenotypes occur in offspring(s) of consanguineous couples. We have collected samples from consanguineous families with different phenotypes of unknown etiology that are compatible with autosomal recessive transmission, in order to identify the responsible functional genomic variation. 42 families of different ethnic background have been collected so far. From each family, DNA from the patient(s), unaffected siblings and the parents is extracted. Samples are i/analyzed by array-CGH for the detection of homozygous deletions; ii/genotyped with a 720K SNP-array in order to identify Runs of Homozygosity and the areas of the genome that could include the causative variant; iii/exome sequenced (one affected individual/family). Mean coverage is 130x and 98.2% of the coding region of RefSeq is covered at least 8x. By comparing the genotyping and sequencing data, we found that Single Nucleotide Variants (that passed the quality threshold) were detected with a specificity of 99.95%, sensitivity of 97.7%, Positive Predictive Value 99.2% and Negative Predictive Value 98.6%. On average we identified 21901 variants/exome. So far we analysed 26 families and identified the causative variation in known genes in 3 of them:VLDLR, FKTN and DMP1. In 12 families 23 candidate genes/variants have been identified(more than 1 candidate genes/family). In 11 families the likely molecular defect has not been identified. Consanguineous families provide an opportunity to identify pathogenic variants responsible for recessive phenotypes and rapidly fill in the gap between genotype and phenotype.
Published: 2012

24. An evaluation of the performance of tag SNPs derived from HapMap in a Caucasian population

Author: Maido Remm, Mari Nelis, Philippe Laflamme, Andres Metspalu, Xiayi Ke, Alexandre Montpetit, Reedik Mägi, Thomas J. Hudson, and Lon R. Cardon
Subjects: Estonia, Linkage disequilibrium, Cancer Research, lcsh:QH426-470, Genotype, Population, Genetics/Genetics of Disease, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Linkage Disequilibrium, White People, 03 medical and health sciences, 0302 clinical medicine, Gene Frequency, Homo (Human), Databases, Genetic, Genetics, Humans, International HapMap Project, education, Allele frequency, Molecular Biology, Alleles, Genetics (clinical), Ecology, Evolution, Behavior and Systematics, Genetics/Population Genetics, 030304 developmental biology, education.field_of_study, 0303 health sciences, Genetics/Genome Projects, 030305 genetics & heredity, Haplotype, Chromosome Mapping, Computational Biology, Genetics/Complex Traits, Minor allele frequency, lcsh:Genetics, Genetic Techniques, Haplotypes, Haplotype estimation, 030217 neurology & neurosurgery, Research Article
Abstract: The Haplotype Map (HapMap) project recently generated genotype data for more than 1 million single-nucleotide polymorphisms (SNPs) in four population samples. The main application of the data is in the selection of tag single-nucleotide polymorphisms (tSNPs) to use in association studies. The usefulness of this selection process needs to be verified in populations outside those used for the HapMap project. In addition, it is not known how well the data represent the general population, as only 90–120 chromosomes were used for each population and since the genotyped SNPs were selected so as to have high frequencies. In this study, we analyzed more than 1,000 individuals from Estonia. The population of this northern European country has been influenced by many different waves of migrations from Europe and Russia. We genotyped 1,536 randomly selected SNPs from two 500-kbp ENCODE regions on Chromosome 2. We observed that the tSNPs selected from the CEPH (Centre d'Etude du Polymorphisme Humain) from Utah (CEU) HapMap samples (derived from US residents with northern and western European ancestry) captured most of the variation in the Estonia sample. (Between 90% and 95% of the SNPs with a minor allele frequency of more than 5% have an r 2 of at least 0.8 with one of the CEU tSNPs.) Using the reverse approach, tags selected from the Estonia sample could almost equally well describe the CEU sample. Finally, we observed that the sample size, the allelic frequency, and the SNP density in the dataset used to select the tags each have important effects on the tagging performance. Overall, our study supports the use of HapMap data in other Caucasian populations, but the SNP density and the bias towards high-frequency SNPs have to be taken into account when designing association studies., Synopsis The recent completion of the Haplotype Map (HapMap) project of the human genome provides considerable information on the patterns of variation in the genome of four populations. One of the applications is a description of a set of tags that act as proxies for many other surrounding variants. This will greatly help researchers in their quest to find complex disease genes by reducing the number of genetic variants to test in association studies. To evaluate its usefulness, several aspects of the map, including its transferability to other populations, still needed to be verified experimentally. Using genomic regions where variants had been thoroughly documented in Caucasian samples from Estonia, the researchers found that the transferability of tags is extremely good. The researchers also found that variants with low frequency in the general population (i.e., less than 5%) could not be accurately captured with tags, and that the regional density of variants in the HapMap project had a major impact on the performance of the tags. This research indicates that the HapMap project will be useful, but that careful consideration of hypotheses and study design will be essential for the success of association studies.
Published: 2005

25. Evolution of the pygmy phenotype: evidence of positive selection fro genome-wide scans in African, Asian, and Melanesian pygmies

Author: Elton Kaitokai, Marta Mirazón Lahr, Avis Babalu, Richard Villems, Maggie Belatti, Da-Wei Huang, Luca Pagani, Tiago Antao, Richard A. Lempicki, Alex Cagan, Mari Nelis, Ene Metspalu, Irene Gallego Romero, Toomas Kivisild, Reedik Mägi, Andrea Bamberg Migliano, Clarissa Scholes, Bryony Hopkinshaw, Katharine Siddle, Georgi Hudjashov, Mait Metspalu, Matthew Leavesley, Brad T. Sherman, and Colin N. Shaw
Subjects: Native Hawaiian or Other Pacific Islander, Genotype, Philippines, Population, Black People, Biology, Polymorphism, Single Nucleotide, Short stature, Anthropology, Physical, Papua New Guinea, Asian People, Genetic variation, Genetics, medicine, Humans, education, Genetics (clinical), Ecology, Evolution, Behavior and Systematics, Selection (genetic algorithm), education.field_of_study, Genetic diversity, Natural selection, Genetic Variation, Adaptation, Physiological, Biological Evolution, Body Height, Genetics, Population, Phenotype, Evolutionary biology, Thyroid function, Adaptation, medicine.symptom
Abstract: Human pygmy populations inhabit different regions of the world, from Africa to Melanesia. In Asia, short-statured populations are often referred to as "negritos." Their short stature has been interpreted as a consequence of thermoregulatory, nutritional, and/or locomotory adaptations to life in tropical forests. A more recent hypothesis proposes that their stature is the outcome of a life history trade-off in high-mortality environments, where early reproduction is favored and, consequently, early sexual maturation and early growth cessation have coevolved. Some serological evidence of deficiencies in the growth hormone/insulin-like growth factor axis have been previously associated with pygmies' short stature. Using genome-wide single-nucleotide polymorphism genotype data, we first tested whether different negrito groups living in the Philippines and Papua New Guinea are closely related and then investigated genomic signals of recent positive selection in African, Asian, and Papuan pygmy populations. We found that negritos in the Philippines and Papua New Guinea are genetically more similar to their nonpygmy neighbors than to one another and have experienced positive selection at different genes. These results indicate that geographically distant pygmy groups are likely to have evolved their short stature independently. We also found that selection on common height variants is unlikely to explain their short stature and that different genes associated with growth, thyroid function, and sexual development are under selection in different pygmy groups.

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25 results on '"Mari Nelis"'

1. SARS-CoV-2 dual infection with Delta and Omicron variants in an immunocompetent host: a case report

2. FinnGen: Unique genetic insights from combining isolated population and national health register data

3. Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss

4. The individual and global impact of copy-number variants on complex human traits

5. Assessment of the genetic and clinical determinants of hip fracture risk: Genome-wide association and Mendelian randomization study

6. A cross-disorder dosage sensitivity map of the human genome

7. The Trans-Ancestral Genomic Architecture of Glycaemic Traits

8. Genome-wide association study identifies 48 common genetic variants associated with handedness

9. Estimation of Genetic Correlation via Linkage Disequilibrium Score Regression and Genomic Restricted Maximum Likelihood

10. Age at first birth in women is genetically associated with increased risk of schizophrenia

11. Shared and Unique Components of Human Population Structure and Genome-Wide Signals of Positive Selection in South Asia

12. Balanced reciprocal translocation t(5;13)(q33;q12) and 9q31.1 microduplication in a man suffering from infertility and pollinosis

13. Hundreds of variants clustered in genomic loci and biological pathways affect human height

14. Common variants in KCNN3 are associated with lone atrial fibrillation

15. A Genome-wide Association Study of Lung Cancer Identifies a Region of Chromosome 5p15 Associated with Risk for Adenocarcinoma

16. Alcohol-related cancers and genetic susceptibility in Europe: the ARCAGE project: study samples and data collection

17. Identification of lung cancer histology-specific variants applying Bayesian framework variant prioritization approaches within the TRICL and ILCCO consortia

18. Erratum: Corrigendum: Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer

19. Hearing impairment in Estonia: an algorithm to investigate genetic causes in pediatric patients

20. Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer

21. Genome-wide analysis of BMI in adolescents and young adults reveals additional insight into the effects of genetic loci over the life course

22. A common biological basis of obesity and nicotine addiction

23. 412 Combination of Genomic Technologies and Consanguinity in Order to Identify Pathogenic Variants in Recessive Disorders

24. An evaluation of the performance of tag SNPs derived from HapMap in a Caucasian population

25. Evolution of the pygmy phenotype: evidence of positive selection fro genome-wide scans in African, Asian, and Melanesian pygmies

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