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Next-generation linkage and association methods applied to hypertension: a multifaceted approach to the analysis of sequence data.


ABSTRACT: To realize the full potential of next-generation sequencing, it is important to consider multiple sources of genetic information, including inheritance, association, and bioinformatics. To illustrate the promise of such an approach, we applied our next-generation linkage and association (NGLA) methods to the sequence data of a large 57-member Mexican American family with hypertension. Our results show that OSBPL10--a disease susceptibility gene for dyslipidemia--may also influence systolic blood pressure (SBP). In particular, our NGLA dense single-nucleotide polymorphism (SNP) analysis identified a 2.5-megabase (Mb) region that strongly cosegregates with low SBP (maximum posterior probability of linkage [PPL] = 68%). Furthermore, using the posterior probability of linkage disequilibrium (PPLD), we fine-mapped this region and identified 12 SBP-associated variants (PPLD ranging between 4% and 14%) that comprise a rare, 4-site haplotype. This haplotype extends into the candidate gene, OSBPL10 (oxysterol-binding protein-like 10). In contrast to our NGLA methods, a commonly used filter-based approach identified 23 variants with little evidence for spatial clustering around any particular gene or region of interest.

SUBMITTER: Stewart WC 

PROVIDER: S-EPMC4143636 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Next-generation linkage and association methods applied to hypertension: a multifaceted approach to the analysis of sequence data.

Stewart William Cl WC   Huang Yungui Y   Greenberg David A DA   Vieland Veronica J VJ  

BMC proceedings 20140617 Suppl 1 Genetic Analysis Workshop 18Vanessa Olmo


To realize the full potential of next-generation sequencing, it is important to consider multiple sources of genetic information, including inheritance, association, and bioinformatics. To illustrate the promise of such an approach, we applied our next-generation linkage and association (NGLA) methods to the sequence data of a large 57-member Mexican American family with hypertension. Our results show that OSBPL10--a disease susceptibility gene for dyslipidemia--may also influence systolic blood  ...[more]

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