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Research Report 2: Novel polygenic model (multi-SNP genetic risk factor) helps to find parts of the missing heritability in blood pressure

Lu, X (2010) Research Report 2: Novel polygenic model (multi-SNP genetic risk factor) helps to find parts of the missing heritability in blood pressure. Master's Thesis / Essay, Biology.

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Abstract

Previous study has revealed that diastolic blood pressure (DBP) and systolic blood pressure (SBP) have a high heritability, ranging from 40% to 60%. Several genome-wide association studies have been conducted and discovered 18 associated loci. Compared with the high heritability of DBP and SBP, the proportion of variation explained by these loci is quite small (~0.1%). Researchers have proposed a hypothesis that a large number of single-nucleotide polymorphisms (SNPs) with very small effect carry a large proportion of the missing heritability. In order to testify this hypothesis, we used the polygenic model to quantify the variance explained by multi-SNPs genetic risk factor in DBP and SBP. Due to the fact that GWA result is more accessible than the individual genotype data, we adopted the approximate likelihood method proposed by Toby Johnson, which just needs the GWAS result to quantify the explained variation, instead of using the individual genotype data. First, we confirmed that the approximation multi-SNP model performs equally well as the exact multi-SNP model by using the simulation and the real data from NESDA cohort. Then we used GWA data from Global BPgen and CHARGE consortia and observed that around 0.26% phenotypic variation was contributed by ~2780 SNPs at association P<0.05 for both DBP and SBP, much higher than ~0.1% variation by the established association. We also quantified that DBP associated SNP can explain 0.2% variation of SBP and vice verse. This suggested the shared genetic background between DBP and SBP. The highly shared genetic background between two traits promises that we can find some common causal genes or biological pathway of DBP and SBP which underlies hypertension. Our result confirms that to some extent, part of missing heritability is own to many SNPs with small effect.

Item Type: Thesis (Master's Thesis / Essay)
Degree programme: Biology
Thesis type: Master's Thesis / Essay
Language: English
Date Deposited: 15 Feb 2018 08:03
Last Modified: 15 Feb 2018 08:03
URI: http://fse.studenttheses.ub.rug.nl/id/eprint/12652

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