Beyond Genome-Wide Association Studies: New Strategies for Identifying Genetic Determinants of Hypertension

Xiaoling Wang; Bram P. Prins; Siim Sober; Maris Laan; Harold Snieder

doi:10.1007/s11906-011-0230-y

Beyond Genome-Wide Association Studies: New Strategies for Identifying Genetic Determinants of Hypertension

Xiaoling Wang, Bram P. Prins, Siim Sober, Maris Laan, Harold Snieder^*

^*Corresponding author for this work

Life Course Epidemiology (LCE)

Research output: Contribution to journal › Article › Academic › peer-review

27 Citations (Scopus)

Abstract

Genetic linkage and association methods have long been the most important tools for gene identification in humans. These approaches can either be hypothesis-based (i.e., candidate-gene studies) or hypothesis-free (i.e., genome-wide studies). The first part of this review offers an overview of the latest successes in gene finding for blood pressure (BP) and essential hypertension using these DNA sequence-based discovery techniques. We further emphasize the importance of post-genome-wide association study (post-GWAS) analysis, which aims to prioritize genetic variants for functional follow-up. Whole-genome next-generation sequencing will eventually be necessary to provide a more comprehensive picture of all DNA variants affecting BP and hypertension. The second part of this review discusses promising novel approaches that move beyond the DNA sequence and aim to discover BP genes that are differentially regulated by epigenetic mechanisms, including microRNAs, histone modification, and methylation.

Original language	English
Pages (from-to)	442-451
Number of pages	10
Journal	Current Hypertension Reports
Volume	13
Issue number	6
DOIs	https://doi.org/10.1007/s11906-011-0230-y
Publication status	Published - Dec-2011

Keywords

Linkage analysis
Association analysis
Genome-wide association study
GWAS
Post-GWAS analysis
Next-generation sequencing
Epigenetics
microRNAs
Histone modification
Methylation
Hypertension
Blood pressure
11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-2
BLOOD-PRESSURE VARIATION
SINGLE-NUCLEOTIDE POLYMORPHISMS
SALT-SENSITIVE HYPERTENSION
DNA-METHYLATION CHANGES
BIRTH-WEIGHT
EPIGENETIC REGULATION
ENVIRONMENTAL-FACTORS
AUTONOMIC ACTIVITY
COMMON VARIANTS

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title = "Beyond Genome-Wide Association Studies: New Strategies for Identifying Genetic Determinants of Hypertension",

abstract = "Genetic linkage and association methods have long been the most important tools for gene identification in humans. These approaches can either be hypothesis-based (i.e., candidate-gene studies) or hypothesis-free (i.e., genome-wide studies). The first part of this review offers an overview of the latest successes in gene finding for blood pressure (BP) and essential hypertension using these DNA sequence-based discovery techniques. We further emphasize the importance of post-genome-wide association study (post-GWAS) analysis, which aims to prioritize genetic variants for functional follow-up. Whole-genome next-generation sequencing will eventually be necessary to provide a more comprehensive picture of all DNA variants affecting BP and hypertension. The second part of this review discusses promising novel approaches that move beyond the DNA sequence and aim to discover BP genes that are differentially regulated by epigenetic mechanisms, including microRNAs, histone modification, and methylation.",

keywords = "Linkage analysis, Association analysis, Genome-wide association study, GWAS, Post-GWAS analysis, Next-generation sequencing, Epigenetics, microRNAs, Histone modification, Methylation, Hypertension, Blood pressure, 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-2, BLOOD-PRESSURE VARIATION, SINGLE-NUCLEOTIDE POLYMORPHISMS, SALT-SENSITIVE HYPERTENSION, DNA-METHYLATION CHANGES, BIRTH-WEIGHT, EPIGENETIC REGULATION, ENVIRONMENTAL-FACTORS, AUTONOMIC ACTIVITY, COMMON VARIANTS",

author = "Xiaoling Wang and Prins, {Bram P.} and Siim Sober and Maris Laan and Harold Snieder",

year = "2011",

month = dec,

doi = "10.1007/s11906-011-0230-y",

language = "English",

volume = "13",

pages = "442--451",

journal = "Current Hypertension Reports",

issn = "1522-6417",

publisher = "Springer",

number = "6",

}

TY - JOUR

T1 - Beyond Genome-Wide Association Studies

T2 - New Strategies for Identifying Genetic Determinants of Hypertension

AU - Wang, Xiaoling

AU - Prins, Bram P.

AU - Sober, Siim

AU - Laan, Maris

AU - Snieder, Harold

PY - 2011/12

Y1 - 2011/12

N2 - Genetic linkage and association methods have long been the most important tools for gene identification in humans. These approaches can either be hypothesis-based (i.e., candidate-gene studies) or hypothesis-free (i.e., genome-wide studies). The first part of this review offers an overview of the latest successes in gene finding for blood pressure (BP) and essential hypertension using these DNA sequence-based discovery techniques. We further emphasize the importance of post-genome-wide association study (post-GWAS) analysis, which aims to prioritize genetic variants for functional follow-up. Whole-genome next-generation sequencing will eventually be necessary to provide a more comprehensive picture of all DNA variants affecting BP and hypertension. The second part of this review discusses promising novel approaches that move beyond the DNA sequence and aim to discover BP genes that are differentially regulated by epigenetic mechanisms, including microRNAs, histone modification, and methylation.

AB - Genetic linkage and association methods have long been the most important tools for gene identification in humans. These approaches can either be hypothesis-based (i.e., candidate-gene studies) or hypothesis-free (i.e., genome-wide studies). The first part of this review offers an overview of the latest successes in gene finding for blood pressure (BP) and essential hypertension using these DNA sequence-based discovery techniques. We further emphasize the importance of post-genome-wide association study (post-GWAS) analysis, which aims to prioritize genetic variants for functional follow-up. Whole-genome next-generation sequencing will eventually be necessary to provide a more comprehensive picture of all DNA variants affecting BP and hypertension. The second part of this review discusses promising novel approaches that move beyond the DNA sequence and aim to discover BP genes that are differentially regulated by epigenetic mechanisms, including microRNAs, histone modification, and methylation.

KW - Linkage analysis

KW - Association analysis

KW - Genome-wide association study

KW - GWAS

KW - Post-GWAS analysis

KW - Next-generation sequencing

KW - Epigenetics

KW - microRNAs

KW - Histone modification

KW - Methylation

KW - Hypertension

KW - Blood pressure

KW - 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-2

KW - BLOOD-PRESSURE VARIATION

KW - SINGLE-NUCLEOTIDE POLYMORPHISMS

KW - SALT-SENSITIVE HYPERTENSION

KW - DNA-METHYLATION CHANGES

KW - BIRTH-WEIGHT

KW - EPIGENETIC REGULATION

KW - ENVIRONMENTAL-FACTORS

KW - AUTONOMIC ACTIVITY

KW - COMMON VARIANTS

U2 - 10.1007/s11906-011-0230-y

DO - 10.1007/s11906-011-0230-y

M3 - Article

SN - 1522-6417

VL - 13

SP - 442

EP - 451

JO - Current Hypertension Reports

JF - Current Hypertension Reports

IS - 6

ER -

Beyond Genome-Wide Association Studies: New Strategies for Identifying Genetic Determinants of Hypertension

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Keywords

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