Journal ArticleDOI
Implementing a unified approach to family-based tests of association.
TLDR
A broad class of family‐based association tests that are adjusted for admixture; use either dichotomous or measured phenotypes; accommodate phenotype‐unknown subjects; use nuclear families, sibships or a combination of the two, permit multiple nuclear families from a single pedigree; incorporate di‐ or multi‐allelic marker data; and permit adjustment for covariates and gene‐by‐environment interactions are described.Abstract:
We describe a broad class of family-based association tests that are adjusted for admixture; use either dichotomous or measured phenotypes; accommodate phenotype-unknown subjects; use nuclear families, sibships or a combination of the two, permit multiple nuclear families from a single pedigree; incorporate di- or multi-allelic marker data; allow additive, dominant or recessive models; and permit adjustment for covariates and gene-by-environment interactions. The test statistic is the covariance between a user-specified function of the genotype and a user-specified function of the trait. The distribution of the statistic is computed using the appropriate conditional distribution of offspring genotypes that adjusts for admixture. Genet. Epidemiol. 19(Suppl 1):S36–S42, 2000. © 2000 Wiley-Liss, Inc.read more
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Hundreds of variants clustered in genomic loci and biological pathways affect human height
Hana Lango Allen,Karol Estrada,Guillaume Lettre,Sonja I. Berndt,Michael N. Weedon,Fernando Rivadeneira,Cristen J. Willer,Anne U. Jackson,Sailaja Vedantam,Sailaja Vedantam,Soumya Raychaudhuri,Soumya Raychaudhuri,Teresa Ferreira,Andrew R. Wood,Robert J. Weyant,Ayellet V. Segrè,Ayellet V. Segrè,Elizabeth K. Speliotes,Elizabeth K. Speliotes,Eleanor Wheeler,Nicole Soranzo,Nicole Soranzo,Ju-Hyun Park,Jian Yang,Daniel F. Gudbjartsson,Nancy L. Heard-Costa,Joshua C. Randall,Lu Qi,Albert V. Smith,Reedik Mägi,Tomi Pastinen,Liming Liang,Iris M. Heid,Jian'an Luan,Gudmar Thorleifsson,Thomas W. Winkler,Michael E. Goddard,Michael E. Goddard,Ken Sin Lo,Cameron D. Palmer,Cameron D. Palmer,Tsegaselassie Workalemahu,Yurii S. Aulchenko,Åsa Johansson,Åsa Johansson,M. Carola Zillikens,Mary F. Feitosa,Tõnu Esko,Tõnu Esko,Toby Johnson,Toby Johnson,Toby Johnson,Shamika Ketkar,Peter Kraft,Massimo Mangino,Inga Prokopenko,Devin Absher,Eva Albrecht,Florian Ernst,Nicole L. Glazer,Caroline Hayward,Jouke-Jan Hottenga,Kevin B. Jacobs,Joshua W. Knowles,Zoltán Kutalik,Zoltán Kutalik,Keri L. Monda,Ozren Polasek,Michael Preuss,Nigel W. Rayner,Neil R. Robertson,Valgerdur Steinthorsdottir,Jonathan Tyrer,Benjamin F. Voight,Benjamin F. Voight,Fredrik Wiklund,Jianfeng Xu,Jing Hua Zhao,Dale R. Nyholt,Niina Pellikka,Niina Pellikka,Markus Perola,Markus Perola,John Perry,Ida Surakka,Ida Surakka,Mari Liis Tammesoo,Elizabeth L. Altmaier,Elizabeth L. Altmaier,Najaf Amin,Thor Aspelund,Tushar Bhangale,Gabrielle Boucher,Daniel I. Chasman,Constance Chen,Lachlan J. M. Coin,Mark E. Cooper,Anna L. Dixon,Quince Gibson,Elin Grundberg,Elin Grundberg,Ke Hao,M. Juhani Junttila,Lee M. Kaplan,Johannes Kettunen,Johannes Kettunen,Inke R. König,Tony Kwan,Robert W. Lawrence,Douglas F. Levinson,Mattias Lorentzon,Barbara McKnight,Andrew P. Morris,Martina Müller,Julius S. Ngwa,Shaun Purcell,Shaun Purcell,Suzanne Rafelt,Rany M. Salem,Rany M. Salem,Erika Salvi,Serena Sanna,Jianxin Shi,Ulla Sovio,John R. Thompson,John R. Thompson,Michael C. Turchin,Michael C. Turchin,Liesbeth Vandenput,Dominique J. Verlaan,Veronique Vitart,Charles C. White,Andreas Ziegler,Peter Almgren,Anthony J. Balmforth,Harry Campbell,Lorena Citterio,Alessandro De Grandi,Anna F. Dominiczak,Jubao Duan,Paul Elliott,Roberto Elosua,Johan G. Eriksson,Nelson B. Freimer,Eco J. C. de Geus,Nicola Glorioso,Shen Haiqing,Anna-Liisa Hartikainen,Aki S. Havulinna,Andrew A. Hicks,Jennie Hui,Jennie Hui,Wilmar Igl,Thomas Illig,Antti Jula,Eero Kajantie,Tuomas O. Kilpeläinen,Markku Koiranen,Ivana Kolcic,Seppo Koskinen,Peter Kovacs,Jaana Laitinen,Jianjun Liu,Marja-Liisa Lokki,Ana Marušić,Andrea Maschio,Thomas Meitinger,Antonella Mulas,Guillaume Paré,Alex N. Parker,John F. Peden,Astrid Petersmann,Irene Pichler,Kirsi H. Pietiläinen,Anneli Pouta,Anneli Pouta,Martin Ridderstråle,Jerome I. Rotter,Jennifer G. Sambrook,Jennifer G. Sambrook,Alan R. Sanders,Carsten Oliver Schmidt,Juha Sinisalo,Jan Smit,Heather M. Stringham,G. Bragi Walters,Elisabeth Widen,Sarah H. Wild,Gonneke Willemsen,Laura Zagato,Lina Zgaga,Paavo Zitting,Helene Alavere,Martin Farrall,Wendy L. McArdle,Mari Nelis,Mari Nelis,Marjolein J. Peters,Samuli Ripatti,Samuli Ripatti,Joyce B. J. van Meurs,Katja K.H. Aben,Kristin G. Ardlie,Jacques S. Beckmann,John Beilby,John Beilby,Richard N. Bergman,Sven Bergmann,Sven Bergmann,Francis S. Collins,Daniele Cusi,Martin den Heijer,Gudny Eiriksdottir,Pablo V. Gejman,Alistair S. Hall,Anders Hamsten,Heikki V. Huikuri,Carlos Iribarren,Carlos Iribarren,Mika Kähönen,Jaakko Kaprio,Jaakko Kaprio,Sekar Kathiresan,Sekar Kathiresan,Sekar Kathiresan,Lambertus A. Kiemeney,Thomas D. Kocher,Lenore J. Launer,Terho Lehtimäki,Olle Melander,Thomas H. Mosley,Arthur W. Musk,Arthur W. Musk,Markku S. Nieminen,Christopher J. O'Donnell,Christopher J. O'Donnell,Claes Ohlsson,Ben A. Oostra,Lyle J. Palmer,Lyle J. Palmer,Olli T. Raitakari,Paul M. Ridker,John D. Rioux,Aila Rissanen,Carlo Rivolta,Heribert Schunkert,Alan R. Shuldiner,Alan R. Shuldiner,David S. Siscovick,Michael Stumvoll,Anke Tönjes,Jaakko Tuomilehto,Jaakko Tuomilehto,Gert-Jan B. van Ommen,Jorma Viikari,Andrew C. Heath,Nicholas G. Martin,Grant W. Montgomery,Michael A. Province,Manfred Kayser,Alice M. Arnold,Larry D. Atwood,Eric Boerwinkle,Stephen J. Chanock,Panos Deloukas,Christian Gieger,Henrik Grönberg,Per Hall,Andrew T. Hattersley,Christian Hengstenberg,Wolfgang Hoffman,G. Mark Lathrop,Veikko Salomaa,Stefan Schreiber,Manuela Uda,Dawn M. Waterworth,Alan F. Wright,Themistocles L. Assimes,Inês Barroso,Inês Barroso,Albert Hofman,Karen L. Mohlke,Dorret I. Boomsma,Mark J. Caulfield,L. Adrienne Cupples,Jeanette Erdmann,Caroline S. Fox,Vilmundur Gudnason,Ulf Gyllensten,Tamara B. Harris,Richard B. Hayes,Marjo-Riitta Järvelin,Marjo-Riitta Järvelin,Marjo-Riitta Järvelin,Vincent Mooser,Patricia B. Munroe,Willem H. Ouwehand,Willem H. Ouwehand,Willem H. Ouwehand,Brenda W.J.H. Penninx,Brenda W.J.H. Penninx,Peter P. Pramstaller,Thomas Quertermous,Igor Rudan,Igor Rudan,Nilesh J. Samani,Nilesh J. Samani,Tim D. Spector,Henry Völzke,Hugh Watkins,James F. Wilson,Leif Groop,Talin Haritunians,Frank B. Hu,Robert C. Kaplan,Andres Metspalu,Andres Metspalu,Kari E. North,David Schlessinger,Nicholas J. Wareham,David J. Hunter,Jeffrey R. O'Connell,David P. Strachan,H.-Erich Wichmann,Ingrid B. Borecki,Cornelia M. van Duijn,Eric E. Schadt,Eric E. Schadt,Unnur Thorsteinsdottir,Unnur Thorsteinsdottir,Leena Peltonen,André G. Uitterlinden,Peter M. Visscher,Nilanjan Chatterjee,Ruth J. F. Loos,Michael Boehnke,Mark I. McCarthy,Erik Ingelsson,Cecilia M. Lindgren,Gonçalo R. Abecasis,Kari Stefansson,Kari Stefansson,Timothy M. Frayling,Joel N. Hirschhorn,Joel N. Hirschhorn +344 more
TL;DR: It is shown that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait, and indicates that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
Hundreds of variants clustered in genomic loci and biological pathways affect human height
Hana Lango Allen,Karol Estrada,Guillaume Lettre,Sonja I. Berndt,Michael N. Weedon,Fernando Rivadeneira,Cristen J. Willer,Anne U. Jackson,Sailaja Vedantam,Soumya Raychaudhuri,Teresa Ferreira,Andrew R. Wood,Robert J. Weyant,Ayellet V. Segrè,Elizabeth K. Speliotes,Eleanor Wheeler,Nicole Soranzo,Ju-Hyun Park,Jian Yang,Daniel F. Gudbjartsson,Nancy L. Heard-Costa,Joshua C. Randall,Lu Qi,Albert V. Smith,Reedik Maegi,Tomi Pastinen,Liming Liang,Iris M. Heid,Jian'an Luan,Gudmar Thorleifsson,Thomas W. Winkler,Michael E. Goddard,Ken Sin Lo,Cameron D. Palmer,Tsegaselassie Workalemahu,Yurii S. Aulchenko,Åsa Johansson,M. Carola Zillikens,Mary F. Feitosa,Tõnu Esko,Toby Johnson,Shamika Ketkar,Peter Kraft,Massimo Mangino,Inga Prokopenko,Devin Absher,Eva Albrecht,Florian Ernst,Nicole L. Glazer,Caroline Hayward,Jouke-Jan Hottenga,Kevin B. Jacobs,Joshua W. Knowles,Zoltán Kutalik,Keri L. Monda,Ozren Polasek,Michael Preuss,Nigel W. Rayner,Neil R. Robertson,Valgerdur Steinthorsdottir,Jonathan Tyrer,Benjamin F. Voight,Fredrik Wiklund,Jianfeng Xu,Jing Hua Zhao,Dale R. Nyholt,Niina Pellikka,Markus Perola,John R. B. Perry,Ida Surakka,Mari-Liis Tammesoo,Elizabeth L. Altmaier,Najaf Amin,Thor Aspelund,Tushar Bhangale,Gabrielle Boucher,Daniel I. Chasman,Constance Chen,Lachlan J. M. Coin,Mark E. Cooper,Anna L. Dixon,Quince Gibson,Elin Grundberg,Ke Hao,M. Juhani Junttila,Lee M. Kaplan,Johannes Kettunen,Inke R. Koenig,Tony Kwan,Robert Lawrence,Douglas F. Levinson,Mattias Lorentzon,Barbara McKnight,Andrew P. Morris,Martina Mueller,Julius S. Ngwa,Shaun Purcell,Suzanne Rafelt,Rany M. Salem,Erika Salvi,Serena Sanna,Jianxin Shi,Ulla Sovio,John R. Thompson,Michael C. Turchin,Liesbeth Vandenput,Dominique J. Verlaan,Veronique Vitart,Charles C. White,Andreas Ziegler,Peter Almgren,Anthony J. Balmforth,Harry Campbell,Lorena Citterio,Alessandro De Grandi,Anna F. Dominiczak,Jubao Duan,Paul Elliott,Roberto Elosua,Johan G. Eriksson,Nelson B. Freimer,Eco J. C. de Geus,Nicola Glorioso,Shen Haiqing,Anna-Liisa Hartikainen,Aki S. Havulinna,Andrew A. Hicks,Jennie Hui,Wilmar Igl,Thomas Illig,Antti Jula,Eero Kajantie,Tuomas O. Kilpelaeinen,Markku Koiranen,Ivana Kolcic,Seppo Koskinen,Peter Kovacs,Jaana Laitinen,Jianjun Liu,Marja-Liisa Lokki,Ana Marušić,Andrea Maschio,Thomas Meitinger,Antonella Mulas,Guillaume Paré,Alex N. Parker,John F. Peden,Astrid Petersmann,Irene Pichler,Kirsi H. Pietiläinen,Anneli Pouta,Martin Riddertrale,Jerome I. Rotter,Jennifer G. Sambrook,Alan R. Sanders,Carsten Oliver Schmidt,Juha Sinisalo,Jan Smit,Heather M. Stringham,G. Bragi Walters,Elisabeth Widen,Sarah H. Wild,Gonneke Willemsen,Laura Zagato,Lina Zgaga,Paavo Zitting,Helene Alavere,Martin Farrall,Wendy L. McArdle,Mari Nelis,Marjolein Peters,Samuli Ripatti,Joyce B. J. vVan Meurs,Katja K.H. Aben,Kristin G. Ardlie,Jacques S. Beckmann,John Beilby,Richard N. Bergman,Sven Bergmann,Francis S. Collins,Daniele Cusi,Martin den Heijer,Gudny Eiriksdottir,Pablo V. Gejman,Alistair S. Hall,Anders Hamsten,Heikki V. Huikuri,Carlos Iribarren,Mika Kähönen,Jaakko Kaprio,Sekar Kathiresan,Lambertus A. Kiemeney,Thomas D. Kocher,Lenore J. Launer,Terho Lehtimäki,Olle Melander,Thomas H. Mosley,Arthur W. Musk,Markku S. Nieminen,Christopher J. O'Donnell,Claes Ohlsson,Ben A. Oostra,Lyle J. Palmer,Olli T. Raitakari,Paul M. Ridker,John D. Rioux,Aila Rissanen,Carlo Rivolta,Heribert Schunkert,Alan R. Shuldiner,David S. Siscovick,Michael Stumvoll,Anke Toenjes,Jaakko Tuomilehto,Gert-Jan B. van Ommen,Jorma Viikari,Andrew C. Heath,Nicholas G. Martin,Grant W. Montgomery,Michael A. Province,Manfred Kayser,Alice M. Arnold,Larry D. Atwood,Eric Boerwinkle,Stephen J. Chanock,Panos Deloukas,Christian Gieger,Henrik Grönberg,Per Hall,Andrew T. Hattersley,Christian Hengstenberg,Wolfgang Hoffman,G. Mark Lathrop,Veikko Salomaa,Stefan Schreiber,Manuela Uda,Dawn M. Waterworth,Alan F. Wright,Themistocles L. Assimes,Inês Barroso,Albert Hofman,Karen L. Mohlke,Dorret I. Boomsma,Mark J. Caulfield,L. Adrienne Cupples,Jeanette Erdmann,Caroline S. Fox,Vilmundur Gudnason,Ulf Gyllensten,Tamara B. Harris,Richard B. Hayes,Marjo-Ritta Jarvelin,Vincent Mooser,Patricia B. Munroe,Willem H. Ouwehand,Brenda W.J.H. Penninx,Peter P. Pramstaller,Thomas Quertermous,Igor Rudan,Nilesh J. Samani,Tim D. Spector,Henry Voelzke,Hugh Watkins,James F. Wilson,Leif Groop,Talin Haritunians,Frank B. Hu,Robert C. Kaplan,Andres Metspalu,Kari E. North,David Schlessinger,Nicholas J. Wareham,David J. Hunter,Jeffrey R. O'Connell,David P. Strachan,H. Erich Schadt,Unnur Thorsteinsdottir,Leena Peltonen,André G. Uitterlinden,Peter M. Visscher,Nilanjan Chatterjee,Ruth J. F. Loos,Michael Boehnke,Mark I. McCarthy,Erik Ingelsson,Cecilia M. Lindgren,Gonçalo R. Abecasis,Kari Stefansson,Timothy M. Frayling,Joel N. Hirschhorn +289 more
TL;DR: In this paper, the authors show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait, revealing patterns with important implications for genetic studies of common human diseases and traits.
Journal ArticleDOI
The family based association test method: strategies for studying general genotype--phenotype associations.
TL;DR: It is shown that the RC-TDT is equivalent to a special case of the FBAT method, and it is generalised to dominant, recessive and multi-allelic marker codings.
Journal ArticleDOI
A common genetic variant is associated with adult and childhood obesity.
Alan Herbert,Norman P. Gerry,Matthew B. McQueen,I. M. Heid,Arne Pfeufer,Thomas Illig,H.-Erich Wichmann,H.-Erich Wichmann,Thomas Meitinger,David J. Hunter,David J. Hunter,Frank B. Hu,Frank B. Hu,Graham A. Colditz,Anke Hinney,Johannes Hebebrand,Kerstin Koberwitz,Kerstin Koberwitz,Xiaofeng Zhu,Richard S. Cooper,Kristin G. Ardlie,Helen N. Lyon,Helen N. Lyon,Helen N. Lyon,Joel N. Hirschhorn,Joel N. Hirschhorn,Joel N. Hirschhorn,Nan M. Laird,Marc E. Lenburg,Christoph Lange,Christoph Lange,Michael F. Christman +31 more
TL;DR: A dense whole-genome scan of DNA samples from the Framingham Heart Study participants was used to identify a common genetic variant near the INSIG2 gene associated with obesity, suggesting that common genetic polymorphisms are important determinants of obesity.
Journal ArticleDOI
Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study
Abbas Dehghan,Anna Köttgen,Qiong Yang,Shih-Jen Hwang,W. H. Linda Kao,Fernando Rivadeneira,Eric Boerwinkle,Daniel Levy,Albert Hofman,Brad C. Astor,Emelia J. Benjamin,Cornelia M. van Duijn,Jacqueline C.M. Witteman,Josef Coresh,Caroline S. Fox,Caroline S. Fox +15 more
TL;DR: Three loci in the Framingham cohort and two in the Rotterdam cohort showed genome-wide association with uric acid, and a score based on genes with a putative role in renal urate handling showed a substantial risk for gout.
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TL;DR: A novel variation of the Haplotype Relative Risk is proposed, in order to glean increased information about linkage disequilibrium or allelic associations by analyzing haplotype-based data rather than genotypic data, and it is shown that statistical tests based on this design give much higher power than those based on the original HRR approach.
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General score tests for associations of genetic markers with disease using cases and their parents
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