Multipoint Quantitative-Trait Linkage Analysis in General Pedigrees
Laura Almasy,John Blangero +1 more
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TLDR
It is shown how variance-component linkage methods can be used in pedigrees of arbitrary size and complexity, and a general framework for multipoint identity-by-descent (IBD) probability calculations is developed.Abstract:
Multipoint linkage analysis of quantitative-trait loci (QTLs) has previously been restricted to sibships and small pedigrees. In this article, we show how variance-component linkage methods can be used in pedigrees of arbitrary size and complexity, and we develop a general framework for multipoint identity-by-descent (IBD) probability calculations. We extend the sib-pair multipoint mapping approach of Fulker et al. to general relative pairs. This multipoint IBD method uses the proportion of alleles shared identical by descent at genotyped loci to estimate IBD sharing at arbitrary points along a chromosome for each relative pair. We have derived correlations in IBD sharing as a function of chromosomal distance for relative pairs in general pedigrees and provide a simple framework whereby these correlations can be easily obtained for any relative pair related by a single line of descent or by multiple independent lines of descent. Once calculated, the multipoint relative-pair IBDs can be utilized in variance-component linkage analysis, which considers the likelihood of the entire pedigree jointly. Examples are given that use simulated data, demonstrating both the accuracy of QTL localization and the increase in power provided by multipoint analysis with 5-, 10-, and 20-cM marker maps. The general pedigree variance component and IBD estimation methods have been implemented in the SOLAR (Sequential Oligogenic Linkage Analysis Routines) computer package.read more
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Obesity, central adiposity and cardiometabolic risk factors in children and adolescents: a family-based study.
TL;DR: The objective of this study was to assess genetic and phenotypic correlations of obesity‐related cardiometabolic risk factors in a family‐based cohort.
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Novel loci associated with usual sleep duration: the CHARGE Consortium Genome-Wide Association Study
Daniel J. Gottlieb,Karin Hek,Ting-hsu Chen,Nathaniel F. Watson,Gudny Eiriksdottir,Enda M. Byrne,Enda M. Byrne,Marilyn C. Cornelis,Simon C. Warby,Stefania Bandinelli,Lynn Cherkas,Daniel S. Evans,Hans J. Grabe,Jari Lahti,Man Li,Terho Lehtimäki,Thomas Lumley,Kristin D. Marciante,Louis Pérusse,Bruce M. Psaty,Bruce M. Psaty,John A Robbins,Gregory J. Tranah,Jacqueline M. Vink,Jemma B. Wilk,Jeanette M. Stafford,Claire Bellis,Reiner Biffar,Claude Bouchard,Brian E. Cade,Gary C. Curhan,Johan G. Eriksson,Ralf Ewert,Luigi Ferrucci,Tibor Fülöp,Philip R. Gehrman,Robert Goodloe,Tamara B. Harris,Andrew C. Heath,Dena G. Hernandez,Albert Hofman,Jouke-Jan Hottenga,David J. Hunter,Majken K. Jensen,Andrew D. Johnson,Mika Kähönen,Linda Kao,Peter Kraft,Emma K. Larkin,Diane S. Lauderdale,Annemarie I. Luik,Marco Medici,Grant W. Montgomery,Aarno Palotie,Aarno Palotie,Aarno Palotie,Sanjay R. Patel,Giorgio Pistis,Eleonora Porcu,Eleonora Porcu,Lydia Quaye,Olli T. Raitakari,Susan Redline,Eric B. Rimm,Jerome I. Rotter,Albert V. Smith,Tim D. Spector,Alexander Teumer,André G. Uitterlinden,Marie-Claude Vohl,Elisabeth Widen,Gonneke Willemsen,Terry Young,Xiaoling Zhang,Yongmei Liu,John Blangero,Dorret I. Boomsma,Vilmundur Gudnason,Frank B. Hu,Massimo Mangino,Nicholas G. Martin,George T. O'Connor,George T. O'Connor,Katie L. Stone,Toshiko Tanaka,Jorma Viikari,Sina A. Gharib,Naresh M. Punjabi,Katri Räikkönen,Henry Völzke,Emmanuel Mignot,Henning Tiemeier +91 more
TL;DR: In this article, a genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry, and the strongest association was identified at two loci, located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8.
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Quantitative trait loci on chromosomes 2p, 4p, and 13q influence bone mineral density of the forearm and hip in Mexican Americans.
Candace M. Kammerer,Jennifer L. Schneider,Shelley A. Cole,James E. Hixson,Paul B. Samollow,Jeffrey R. O'Connell,Reina Perez,Thomas D. Dyer,Laura Almasy,John Blangero,Richard L Bauer,Richard L Bauer,Braxton D. Mitchell +12 more
TL;DR: Evidence for QTL on chromosome 4p, affecting forearm BMD overall, and on chromosomes 2p and 13q, affecting hip BMD in men is obtained.
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Association of Variants in RETN With Plasma Resistin Levels and Diabetes-Related Traits in the Framingham Offspring Study
Marie-France Hivert,Alisa K. Manning,Jarred B. McAteer,Josée Dupuis,Caroline S. Fox,L. Adrienne Cupples,James B. Meigs,Jose C. Florez +7 more
TL;DR: SNPs in the 3′ region of RETN are associated with resistin levels, and one of them is also associated with glucose levels, although replication is needed.
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Novel family-based approaches to genetic risk in thrombosis
TL;DR: This review details the reasons why the field would benefit from a more vigorous pursuit of modern family‐based genetic studies and identifies the underlying quantitative trait loci (QTLs) that influence disease susceptibility.
References
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Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results
Eric S. Lander,Leonid Kruglyak +1 more
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Eric S. Lander,Philip Green +1 more
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