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Genome-wide linkage and association analysis of cardiometabolic phenotypes in Hispanic Americans
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نویسنده
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Hellwege Jacklyn N ,Palmer Nicholette D ,Dimitrov Latchezar ,Keaton Jacob M ,Tabb Keri L ,Sajuthi Satria ,Taylor Kent D ,Ng Maggie C Y ,Speliotes Elizabeth K ,Hawkins Gregory A ,Long Jirong ,Chen Yii-Der Ida ,Lorenzo Carlos ,Norris Jill M ,Rotter Jerome I ,Langefeld Carl D ,Wagenknecht Lynne E ,Bowden Donald W
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منبع
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journal of human genetics - 2017 - دوره : 62 - شماره : 2 - صفحه:175 -184
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چکیده
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Linkage studies of complex genetic diseases have been largely replaced by genome-wide association studies, due in part to limited success in complex trait discovery. however, recent interest in rare and low-frequency variants motivates re-examination of family-based methods. in this study, we investigated the performance of two-point linkage analysis for over 1.6 million single-nucleotide polymorphisms (snps) combined with single variant association analysis to identify high impact variants, which are both strongly linked and associated with cardiometabolic traits in up to 1414 hispanics from the insulin resistance atherosclerosis family study (irasfs). evaluation of all 50 phenotypes yielded 83 557 000 lod (logarithm of the odds) scores, with 9214 lod scores ⩾3.0, 845 ⩾4.0 and 89 ⩾5.0, with a maximal lod score of 6.49 (rs12956744 in the lama1 gene for tumor necrosis factor-α (tnfα) receptor 2). twenty-seven variants were associated with p<0.005 as well as having an lod score >4, including variants in the nfib gene under a linkage peak with tnfα receptor 2 levels on chromosome 9. linkage regions of interest included a broad peak (31 mb) on chromosome 1q with acute insulin response (max lod=5.37). this region was previously documented with type 2 diabetes in family-based studies, providing support for the validity of these results. overall, we have demonstrated the utility of two-point linkage and association in comprehensive genome-wide array-based snp genotypes.
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آدرس
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Winston-Salem, USA, Winston-Salem, Department of Biochemistry, Molecular Genetics and Genomics Program, USA, Winston-Salem, USA, Winston-Salem, Molecular Genetics and Genomics Program, USA, Winston-Salem, Department of Biochemistry, USA, Winston-Salem, Molecular Genetics and Genomics Program, Department of Biostatistical Sciences, USA, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, USA, Winston-Salem, USA, University of Michigan, Department of Internal Medicine, Division of Gastroenterology, Department of Computational Medicine and Bioinformatics, USA, Winston-Salem, USA, Vanderbilt University Medical Center, Division of Epidemiology, Department of Medicine, USA, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, USA, University of Texas Health Science Center, Department of Medicine, USA, University of Colorado Denver, Department of Epidemiology, USA, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, USA, Winston-Salem, Molecular Genetics and Genomics Program, Department of Biostatistical Sciences, USA, Winston-Salem, Division of Public Health Sciences, USA, Winston-Salem, Department of Biochemistry, USA
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Authors
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