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      Genome-wide association analysis with selective genotyping identifies candidate loci for adult height at 8q21.13 and 15q22.33-q23 in Mongolians

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          Abstract

          We performed a genome-wide association study with 23,465 microsatellite markers to identify genes related to adult height. Selective genotyping was applied to extremely tall and extremely short individuals from the Khalkh-Mongolian population. Two loci, 8q21.13 and 15q22.33, which showed the strongest association with microsatellites were subjected to further analyses of SNPs in 782 tall and 773 short individuals. The most significant association was observed with SNP rs2220456 at 8q21.13 ( P = 0.000016). In the LD block at 15q22.32, SNP rs8038652 located in intron 1 of IQCH was strongly associated ( P = 0.0003), especially the AA genotype of the SNP under a recessive model was strongly associated with adult height ( P = 0.000046).

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          Mapping mendelian factors underlying quantitative traits using RFLP linkage maps.

          Eric S. Lander, D Botstein, E Lander … (1989)
          The advent of complete genetic linkage maps consisting of codominant DNA markers [typically restriction fragment length polymorphisms (RFLPs)] has stimulated interest in the systematic genetic dissection of discrete Mendelian factors underlying quantitative traits in experimental organisms. We describe here a set of analytical methods that modify and extend the classical theory for mapping such quantitative trait loci (QTLs). These include: (i) a method of identifying promising crosses for QTL mapping by exploiting a classical formula of SEWALL WRIGHT; (ii) a method (interval mapping) for exploiting the full power of RFLP linkage maps by adapting the approach of LOD score analysis used in human genetics, to obtain accurate estimates of the genetic location and phenotypic effect of QTLs; and (iii) a method (selective genotyping) that allows a substantial reduction in the number of progeny that need to be scored with the DNA markers. In addition to the exposition of the methods, explicit graphs are provided that allow experimental geneticists to estimate, in any particular case, the number of progeny required to map QTLs underlying a quantitative trait.
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            The future of genetic studies of complex human diseases.

            N Risch, K Merikangas (1996)
            Article 0 comments Cited 371 times – based on 0 reviews     Review now
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              Many sequence variants affecting diversity of adult human height.

              Daniel Gudbjartsson, G Walters, Gudmar Thorleifsson … (2008)
              Adult human height is one of the classical complex human traits. We searched for sequence variants that affect height by scanning the genomes of 25,174 Icelanders, 2,876 Dutch, 1,770 European Americans and 1,148 African Americans. We then combined these results with previously published results from the Diabetes Genetics Initiative on 3,024 Scandinavians and tested a selected subset of SNPs in 5,517 Danes. We identified 27 regions of the genome with one or more sequence variants showing significant association with height. The estimated effects per allele of these variants ranged between 0.3 and 0.6 cm and, taken together, they explain around 3.7% of the population variation in height. The genes neighboring the identified loci cluster in biological processes related to skeletal development and mitosis. Association to three previously reported loci are replicated in our analyses, and the strongest association was with SNPs in the ZBTB38 gene.
              Article 0 comments Cited 229 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                : tekimura@is.icc.u-tokai.ac.jp
                : +81-463-931121 , +81-463-948884 , hinoko@is.icc.u-tokai.ac.jp
                Journal
                Journal ID (nlm-ta): Hum Genet
                Title: Human Genetics
                Publisher: Springer-Verlag (Berlin/Heidelberg )
                ISSN (Print): 0340-6717
                ISSN (Electronic): 1432-1203
                Publication date (Electronic): 20 May 2008
                Publication date (Print): July 2008
                Volume: 123
                Issue: 6
                Pages: 655-660
                Affiliations
                [1 ]Department of Molecular Life Science and Molecular Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193 Japan
                [2 ]Central Scientific Research Laboratory, National Institute of Medicine, Ulaanbaatar, Mongolia
                Article
                Publisher ID: 512
                DOI: 10.1007/s00439-008-0512-x
                PMC ID: 2440952
                PubMed ID: 18491143
                SO-VID: 0e2b81fe-ae8f-485b-a3d6-52f21205b114
                Copyright © © The Author(s) 2008
                History
                Date received : 6 February 2008
                Date accepted : 12 May 2008
                Categories
                Subject: Short Report
                Custom metadata
                issue-copyright-statement © Springer-Verlag 2008

                ScienceOpen disciplines: Genetics
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                ScienceOpen disciplines: Genetics

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