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Genome-wide linkage and association analysis of cardiometabolic phenotypes in Hispanic Americans.

Citation
Hellwege, J. N., et al. “Genome-Wide Linkage And Association Analysis Of Cardiometabolic Phenotypes In Hispanic Americans.”. Journal Of Human Genetics, pp. 175-184.
Center UCSD-UCLA
Author Jacklyn N Hellwege, Nicholette D Palmer, Latchezar Dimitrov, Jacob M Keaton, Keri L Tabb, Satria Sajuthi, Kent D Taylor, Maggie C Y Ng, Elizabeth K Speliotes, Gregory A Hawkins, Jirong Long, Yii-Der Ida Chen, Carlos Lorenzo, Jill M Norris, Jerome I Rotter, Carl D Langefeld, Lynne E Wagenknecht, Donald W Bowden
Abstract

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.

Year of Publication
2017
Journal
Journal of human genetics
Volume
62
Issue
2
Number of Pages
175-184
Date Published
02/2017
ISSN Number
1435-232X
DOI
10.1038/jhg.2016.103
Alternate Journal
J. Hum. Genet.
PMID
27535031
PMCID
PMC5266668
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