Genome-Wide Linkage and Regional Association Study of Blood Pressure Response to the Cold Pressor Test in Han Chinese

Yang, Xueli; Gu, Dongfeng; He, Jiang; Hixson, James E.; Rao, D. C.; Lu, Fanghong; Mu, Jianjun; Jaquish, Cashell E.; Chen, Jing; Huang, Jianfeng; Shimmin, Lawrence C.; Rice, Treva; Chen, Jichun; Wu, Xigui; Liu, Depei; Kelly, Tanika N.

doi:10.1161/circgenetics.113.000332

Cited by 6 publications

(4 citation statements)

References 49 publications

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“…TMC2 is a potential ion channel required for the mechano-transduction of cochlear hair cells [42]. A study in the Han Chinese population reported that TMC2 was among the top genes associated with BP response to the cold pressor test (CPT), which is associated with an increased risk of cardiovascular disease [43].…”

Section: Discussionmentioning

confidence: 99%

Admixture mapping identifies genetic regions associated with blood pressure phenotypes in African Americans

Shriner

Hansen

et al. 2020

PLoS ONE

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Hypertension occurs at a higher rate in African Americans than in European Americans. Based on the assumption that causal variants are more frequently found on DNA segments inherited from the ancestral population with higher disease risk, we employed admixture mapping to identify genetic loci with excess local African ancestry associated with blood pressure. Chromosomal regions 1q21.2-21.3, 4p15.1, 19q12 and 20p13 were significantly associated with diastolic blood pressure (β = 5.28,-7.94,-6.82 and 5.89, P-value = 6.39E-04, 2.07E-04, 6.56E-05 and 5.04E-04, respectively); 1q21.2-21.3 and 19q12 were also significantly associated with mean arterial pressure (β = 5.86 and-6.40, P-value = 5.32E-04 and 6.37E-04, respectively). We further selected SNPs that had large allele frequency differences within these regions and tested their association with blood pressure. SNP rs4815428 was significantly associated with diastolic blood pressure after Bonferroni correction (β =-2.42, P-value = 9.57E-04), and it partially explained the admixture mapping signal at 20p13. SNPs rs771205 (β =-1.99, P-value = 3.37E-03), rs3126067, rs2184953 and rs58001094 (the latter three exhibit strong linkage disequilibrium, β =-2.3, P-value = 1.4E-03) were identified to be significantly associated with mean arterial pressure, and together they fully explained the admixture signal at 1q21.2-21.3. Although no SNP at 4p15.1 showed large ancestral allele frequency differences in our dataset, we detected association at low-frequency African-specific variants that mapped predominantly to the gene PCDH7, which is most highly expressed in aorta. Our results suggest that these regions may harbor genetic variants that contribute to the different prevalence of hypertension.

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Section: Discussionmentioning

confidence: 99%

Admixture mapping identifies genetic regions associated with blood pressure phenotypes in African Americans

Shriner

Hansen

et al. 2020

PLoS ONE

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“…There is accumulating evidence identifying products of the serine/threonine kinase 35 ( STK35 ) gene as suitable targets for diagnosis or intervention in cardiac pathologies ( Lamore et al, 2017 ; Yang et al, 2014 ), colorectal and other cancers ( Capra et al, 2006 ) and malaria ( Prudêncio et al, 2008 ), hence investigations of its physiological roles are of great interest. STK35 was originally identified as a binding partner of the PDZ-LIM protein, CLP-36, and named Clik1, for CLP-36 interacting kinase 1.…”

Section: Introductionmentioning

confidence: 99%

TheStk35locus contributes to normal gametogenesis and encodes a lncRNA responsive to oxidative stress

et al. 2018

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Serine/threonine kinase 35 (STK35) is a recently identified human kinase with an autophosphorylation function, linked functionally to actin stress fibers, cell cycle progression and survival. STK35 has previously been shown to be highly expressed in human testis, and we demonstrated its regulation by nuclear-localized importin α2 in HeLa cells. The present study identifies progressive expression from the STK35 locus of two coding mRNA isoforms and one long non-coding RNA (lncRNA) in mouse testis during spermatogenesis, indicating their tightly controlled synthesis. Additionally, lncRNA transcripts are increased by exposure to oxidative stress in mouse GC-1 germ cell line. STK35 knockout (KO) mice lacking all three RNAs are born at sub-Mendelian frequency, and adults manifest both male and female germline deficiency. KO males exhibit no or partial spermatogenesis in most testis tubule cross-sections; KO ovaries are smaller and contain fewer follicles. Eyes of KO mice display phenotypes ranging from gross deformity to mild goniodysgenesis or iridocorneal angle malformation, to overtly normal. These findings demonstrate the tight regulation of transcription from the STK35 locus and its central importance to fertility, eye development and cell responses to oxidative stress.

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“…A genome-wide linkage study followed by single nucleotide polymorphism screen of linked regions identified variants in the MCM8, SLC23A2 and STK35 genes associated with the blood pressure response to the cold pressor test, via unknown pathways. (90)…”

Section: Autonomic Tone: Definition Measurement Heritability and Umentioning

confidence: 99%

Genomics of Cardiovascular Measures of Autonomic Tone

Sigurdsson

Waldron

Bortsov

et al. 2018

Journal of Cardiovascular Pharmacology

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The autonomic nervous system exerts broad control over the involuntary functions of the human body through complex equilibrium between sympathetic and parasympathetic tone. Imbalance in this equilibrium is associated with a multitude of cardiovascular outcomes, including mortality. The cardiovascular static state of this equilibrium can be quantified using physiological parameters such as heart rate (HR), blood pressure, and by spectral analysis of HR variability. Here, we review the current state of knowledge of the genetic background of cardiovascular measurements of autonomic tone. For most parameters of autonomic tone, a large portion of variability is explained by genetic heritability. Many of the static parameters of autonomic tone have also been studied through candidate-gene approach, yielding some insight into how genotypes of adrenergic receptors affect variables such as HR. Genome-wide approaches in large cohorts similarly exist for static variables such as HR and blood pressure but less is known about the genetic background of the dynamic and more specific measurements, such as HR variability. Furthermore, because most autonomic measures are likely polygenic, pathway analyses and modeling of polygenic effects are critical. Future work will hopefully explain the control of autonomic tone and guide individualized therapeutic interventions.

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Genome-Wide Linkage and Regional Association Study of Blood Pressure Response to the Cold Pressor Test in Han Chinese

Cited by 6 publications

References 49 publications

Admixture mapping identifies genetic regions associated with blood pressure phenotypes in African Americans

Admixture mapping identifies genetic regions associated with blood pressure phenotypes in African Americans

TheStk35locus contributes to normal gametogenesis and encodes a lncRNA responsive to oxidative stress

Genomics of Cardiovascular Measures of Autonomic Tone

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