What is a functional locus? Understanding the genetic basis of complex phenotypic traits.
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TLDR
It is postulated that functional loci may include different positions in the DNA sequence and, variants of the same functional locus may be located in different physical positions along the genome and, the observed effect of any particular genetic variant will be reduced compared to its true effect.About:
This article is published in Medical Hypotheses.The article was published on 2011-05-01 and is currently open access. It has received 8 citations till now. The article focuses on the topics: Common disease-common variant & Genome-wide association study.read more
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Is atypical rhythm a risk factor for developmental speech and language disorders
Enikő Ladányi,Valentina Persici,Valentina Persici,Valentina Persici,Anna Fiveash,Barbara Tillmann,Reyna L. Gordon +6 more
TL;DR: If a significant body of evidence is found to support the Atypical Rhythm Risk Hypothesis, it is suggested that new risk factor models that incorporate atypical rhythm to predict the risk of developing speech/language disorders could be envisioned.
Journal ArticleDOI
Strengthening Causal Inference for Complex Disease Using Molecular Quantitative Trait Loci.
TL;DR: This work has shown that genetic variants associated with intermediate traits, termed molecular quantitative trait loci (molQTLs), can be used as instrumental variables in a Mendelian randomization approach to identify the causal features and mechanisms of complex traits.
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Identifying Multi-Omics Causers and Causal Pathways for Complex Traits.
TL;DR: This article analytically proves that the more remote an omics level is from a physiological trait, the smaller the magnitude of their correlation is and integrates RNA and protein expressions with DNA data and causal inference to gain a full understanding of how genetic causal variants contribute to phenotype variations.
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Redundant enhancers and causal variants in the TCF7L2 gene.
TL;DR: The physical overlap between multiple enhancer elements and TCF7L2 variants suggests that this gene may carry more than one causal variant related to the development of T2D.
Journal ArticleDOI
Use of alternative promoters may hide genetic effects on phenotypic traits.
TL;DR: A simple mathematical model predicts that in presence of person-to-person variation in the use of alternative promoters the observable effects of genetic variants located inside promoters will be smaller than their actual effects and genetic variation because of those observed polymorphisms will be reduced.
References
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A genome-wide association study identifies novel risk loci for type 2 diabetes
Robert Sladek,Ghislain Rocheleau,Johan Rung,Christian Dina,Lishuang Shen,David Serre,Philippe Boutin,Daniel Vincent,Alexandre Belisle,Samy Hadjadj,Beverley Balkau,Barbara Heude,Guillaume Charpentier,Thomas J. Hudson,Thomas J. Hudson,Alexandre Montpetit,Alexey V. Pshezhetsky,Marc Prentki,Barry I. Posner,David J. Balding,David Meyre,Constantin Polychronakos,Philippe Froguel,Philippe Froguel +23 more
TL;DR: Four loci containing variants that confer type 2 diabetes risk are identified and constitute proof of principle for the genome-wide approach to the elucidation of complex genetic traits.
Journal ArticleDOI
Genome-Wide Association Analysis Identifies Loci for Type 2 Diabetes and Triglyceride Levels
Richa Saxena,Benjamin F. Voight,Valeriya Lyssenko,Noël P. Burtt,Paul I.W. de Bakker,Hong Chen,Jeffrey J. Roix,Sekar Kathiresan,Joel N. Hirschhorn,Mark J. Daly,Thomas E. Hughes,Leif Groop,David Altshuler,Peter Almgren,Jose C. Florez,Joanne M. Meyer,Kristin Ardlie,Kristina Bengtsson Boström,Bo Isomaa,Guillaume Lettre,Ulf Lindblad,Helen N. Lyon,Olle Melander,Christopher Newton-Cheh,Peter Nilsson,Marju Orho-Melander,Lennart Råstam,Elizabeth K. Speliotes,Marja-Riitta Taskinen,Tiinamaija Tuomi,Candace Guiducci,Anna Berglund,Joyce Carlson,Lauren Gianniny,Rachel Hackett,Liselotte Hall,Johan Holmkvist,Esa Laurila,Marketa Sjögren,Maria Sterner,Aarti Surti,Margareta Svensson,Malin Svensson,Ryan Tewhey,Brendan Blumenstiel,Melissa Parkin,Matthew DeFelice,Rachel Barry,Wendy Brodeur,Jody Camarata,Nancy Chia,Mary Fava,John G. Gibbons,Bob Handsaker,Claire M. Healy,Kieu Nguyen,Casey Gates,Carrie Sougnez,Diane Gage,Marcia M. Nizzari,Stacey Gabriel,Gung-Wei Chirn,Qicheng Ma,Hemang Parikh,Delwood Richardson,Darrell O. Ricke,Shaun Purcell +66 more
TL;DR: The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases.
Journal ArticleDOI
A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants.
Laura J. Scott,Karen L. Mohlke,Lori L. Bonnycastle,Cristen J. Willer,Yun Li,William L. Duren,Michael R. Erdos,Heather M. Stringham,Peter S. Chines,Anne U. Jackson,Ludmila Prokunina-Olsson,Chia-Jen Ding,Amy J. Swift,Narisu Narisu,Tianle Hu,Randall Pruim,Rui Xiao,Xiao-Yi Li,Karen N. Conneely,Nancy Riebow,Andrew G. Sprau,Maurine Tong,Peggy P. White,Kurt N. Hetrick,Michael W. Barnhart,Craig W. Bark,Janet L. Goldstein,Lee Watkins,Fang Xiang,Jouko Saramies,Thomas A. Buchanan,Richard M. Watanabe,Timo T. Valle,Leena Kinnunen,Gonçalo R. Abecasis,Elizabeth W. Pugh,Kimberly F. Doheny,Richard N. Bergman,Jaakko Tuomilehto,Francis S. Collins,Michael Boehnke +40 more
TL;DR: The number of T2D loci now confidently identified to at least 10 is confirmed, and it is confirmed that variants near TCF7L2, SLC30A8, HHEX, FTO, PPARG, and KCNJ11 are associated with T1D risk.
Journal ArticleDOI
Genome-wide association study identifies novel breast cancer susceptibility loci
Douglas F. Easton,Karen A. Pooley,Alison M. Dunning,Paul D.P. Pharoah,Deborah J. Thompson,Dennis G. Ballinger,Jeffery P. Struewing,Jonathan J. Morrison,Helen I. Field,Robert Luben,Nicholas J. Wareham,Shahana Ahmed,Catherine S. Healey,Richard Bowman,Kerstin B. Meyer,Christopher A. Haiman,Laurence K. Kolonel,Brian E. Henderson,Loic Le Marchand,Paul Brennan,Suleeporn Sangrajrang,Valerie Gaborieau,Fabrice Odefrey,Chen-Yang Shen,Pei-Ei Wu,Hui-Chun Wang,Diana Eccles,D. Gareth Evans,Julian Peto,Olivia Fletcher,Nichola Johnson,Sheila Seal,Michael R. Stratton,Nazneen Rahman,Georgia Chenevix-Trench,Georgia Chenevix-Trench,Stig E. Bojesen,Børge G. Nordestgaard,C K Axelsson,Montserrat Garcia-Closas,Louise A. Brinton,Stephen J. Chanock,Jolanta Lissowska,Beata Peplonska,Heli Nevanlinna,Rainer Fagerholm,H Eerola,Daehee Kang,Keun-Young Yoo,Dong-Young Noh,Sei Hyun Ahn,David J. Hunter,Susan E. Hankinson,David G. Cox,Per Hall,Sara Wedrén,Jianjun Liu,Yen-Ling Low,Natalia Bogdanova,Peter Schu¨rmann,Do¨rk Do¨rk,Rob A. E. M. Tollenaar,Catharina E. Jacobi,Peter Devilee,Jan G. M. Klijn,Alice J. Sigurdson,Michele M. Doody,Bruce H. Alexander,Jinghui Zhang,Angela Cox,Ian W. Brock,Gordon MacPherson,Malcolm W.R. Reed,Fergus J. Couch,Ellen L. Goode,Janet E. Olson,Hanne Meijers-Heijboer,Hanne Meijers-Heijboer,Ans M.W. van den Ouweland,André G. Uitterlinden,Fernando Rivadeneira,Roger L. Milne,Gloria Ribas,Anna González-Neira,Javier Benitez,John L. Hopper,Margaret R. E. McCredie,Margaret R. E. McCredie,Margaret R. E. McCredie,Melissa C. Southey,Melissa C. Southey,Graham G. Giles,Chris Schroen,Christina Justenhoven,Christina Justenhoven,Hiltrud Brauch,Hiltrud Brauch,Ute Hamann,Yon-Dschun Ko,Amanda B. Spurdle,Jonathan Beesley,Xiaoqing Chen,_ kConFab,Arto Mannermaa,Veli-Matti Kosma,Vesa Kataja,Jaana M. Hartikainen,Nicholas E. Day,David Cox,Bruce A.J. Ponder +109 more
TL;DR: To identify further susceptibility alleles, a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls was conducted, followed by a third stage in which 30 single nucleotide polymorphisms were tested for confirmation.
Journal ArticleDOI
Six new loci associated with body mass index highlight a neuronal influence on body weight regulation
Cristen J. Willer,Elizabeth K. Speliotes,Elizabeth K. Speliotes,Ruth J. F. Loos,Shengxu Li,Cecilia M. Lindgren,Iris M. Heid,Sonja I. Berndt,Amanda F. Elliott,Amanda F. Elliott,Anne U. Jackson,Claudia Lamina,Guillaume Lettre,Guillaume Lettre,Noha Lim,Helen N. Lyon,Helen N. Lyon,Steven A. McCarroll,Steven A. McCarroll,Konstantinos A. Papadakis,Lu Qi,Joshua C. Randall,Rosa Maria Roccasecca,Serena Sanna,Paul Scheet,Michael N. Weedon,Eleanor Wheeler,Jing Hua Zhao,Leonie C. Jacobs,Inga Prokopenko,Nicole Soranzo,Nicole Soranzo,Toshiko Tanaka,Nicholas J. Timpson,Peter Almgren,Amanda J. Bennett,Richard N. Bergman,Sheila Bingham,Lori L. Bonnycastle,Morris Brown,Noël P. Burtt,Peter S. Chines,Lachlan J. M. Coin,Francis S. Collins,John M. C. Connell,Cyrus Cooper,George Davey Smith,Elaine M. Dennison,Parimal Deodhar,Paul Elliott,Michael R. Erdos,Karol Estrada,David M. Evans,Lauren Gianniny,Christian Gieger,Christopher J. Gillson,Candace Guiducci,Rachel Hackett,David Hadley,Alistair S. Hall,Aki S. Havulinna,Johannes Hebebrand,Albert Hofman,Bo Isomaa,Kevin B. Jacobs,Toby Johnson,Toby Johnson,Pekka Jousilahti,Zorica Jovanovic,Zorica Jovanovic,Kay-Tee Khaw,Peter Kraft,Mikko Kuokkanen,Mikko Kuokkanen,Johanna Kuusisto,Jaana Laitinen,Edward G. Lakatta,Jian'an Luan,Robert Luben,Massimo Mangino,Wendy L. McArdle,Thomas Meitinger,Antonella Mulas,Patricia B. Munroe,Narisu Narisu,Andy R Ness,Kate Northstone,Stephen O'Rahilly,Stephen O'Rahilly,Carolin Purmann,Carolin Purmann,Matthew G. Rees,Martin Ridderstråle,Susan M. Ring,Fernando Rivadeneira,Aimo Ruokonen,Manjinder S. Sandhu,Manjinder S. Sandhu,Jouko Saramies,Laura J. Scott,Angelo Scuteri,Kaisa Silander,Matthew A. Sims,Kijoung Song,Jonathan Stephens,Suzanne Stevens,Heather M. Stringham,Y. C. Loraine Tung,Y. C. Loraine Tung,Timo T. Valle,Cornelia M. van Duijn,Karani Santhanakrishnan Vimaleswaran,Karani Santhanakrishnan Vimaleswaran,Peter Vollenweider,Gérard Waeber,Chris Wallace,Richard M. Watanabe,Dawn M. Waterworth,Nicholas A. Watkins,Jacqueline C. M. Witteman,Eleftheria Zeggini,Guangju Zhai,M. Carola Zillikens,David Altshuler,David Altshuler,Mark J. Caulfield,Stephen J. Chanock,I. Sadaf Farooqi,I. Sadaf Farooqi,Luigi Ferrucci,Jack M. Guralnik,Andrew T. Hattersley,Frank B. Hu,Marjo-Riitta Järvelin,Markku Laakso,Vincent Mooser,Ken K. Ong,Willem H. Ouwehand,Willem H. Ouwehand,Veikko Salomaa,Nilesh J. Samani,Tim D. Spector,Tiinamaija Tuomi,Jaakko Tuomilehto,Manuela Uda,André G. Uitterlinden,Nicholas J. Wareham,Panagiotis Deloukas,Timothy M. Frayling,Leif Groop,Leif Groop,Richard B. Hayes,David J. Hunter,David J. Hunter,Karen L. Mohlke,Leena Peltonen,Leena Peltonen,Leena Peltonen,David Schlessinger,David P. Strachan,H-Erich Wichmann,Mark I. McCarthy,Michael Boehnke,Inês Barroso,Gonçalo R. Abecasis,Joel N. Hirschhorn,Joel N. Hirschhorn +166 more
TL;DR: Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.