Genome-wide linkage and association scans for pulse pressure in Chinese twins

Zhang, Dongfeng; Pang, Zengchang; Li, Shuxia; Jiang, Wenjie; Wang, Shaojie; Thomassen, Mads; Hjelmborg, Jacob; Kruse, Torben A.; Kyvik, Kirsten Ohm; Christensen, Kaare; Zhu, Gu; Tan, Qihua

doi:10.1038/hr.2012.90

Cited by 12 publications

(10 citation statements)

References 38 publications

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“…5, 6, 8, 9, 39-41 In this study, in contrast with the rare variant result, we did not identify novel common variants that significantly influenced BP levels. We showed consistent results for four common BP SNPs, located in ULK4 , SLC39A8 , HFE , SH2B3 , that were reported by the ICBP consortium 6 and were captured in our whole exome sequencing.…”

Section: Discussioncontrasting

confidence: 71%

Rare Exome Sequence Variants in CLCN6 Reduce Blood Pressure Levels and Hypertension Risk

Yu¹,

Pulit²,

Hwang³

et al. 2016

Circ Cardiovasc Genet

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Background Rare genetic variants influence blood pressure (BP). Methods and Results Whole exome sequencing was performed on DNA samples from 17,956 individuals of European and African ancestry (14,497 first stage and 3,459 second stage discovery) to examine the impact of rare variants on hypertension and four BP traits: systolic and diastolic BP (SBP, DBP), pulse pressure (PP), and mean arterial pressure (MAP). Tests of ∼170,000 common variants (minor allele frequency, MAF, ≥1%, statistical significance P≤2.9×10-7) and gene-based tests of rare variants (MAF<1%, ∼17,000 genes, statistical significance P≤1.5×10-6) were evaluated for each trait and ancestry, followed by multiethnic meta-analyses. In the first stage discovery, rare coding variants (splicing, stop-gain, stop-loss, nonsynonymous variants, or indels) in CLCN6 were associated with lower DBP (cumulative MAF=1.3%, β=-3.20, P=4.1×10-6), and were independent of a nearby common variant (rs17367504) previously associated with BP. CLCN6 rare variants were also associated with lower SBP (β=-4.11, P=2.8×10-4), MAP (β=-3.50, P=8.9×10-6), and reduced hypertension risk (odds ratio=0.72, P=0.017). Meta-analysis of the two-stage discovery samples showed that CLCN6 was associated with lower DBP at exome-wide significance (cumulative MAF=1.1%, β=-3.30, P=5.0×10-7). Conclusions These findings implicate the effect of rare coding variants in CLCN6 in BP variation, and offer new insights into BP regulation.

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Section: Discussioncontrasting

confidence: 71%

Rare Exome Sequence Variants in CLCN6 Reduce Blood Pressure Levels and Hypertension Risk

Yu¹,

Pulit²,

Hwang³

et al. 2016

Circ Cardiovasc Genet

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“…We found that the brown module was strongly overrepresented with genes associated with genetic risk for disease ( P = 6.3 × 10 −14 , Odds Ratio = 2[1.7–2.4]), as were the brown hub genes specifically ( P = 6.1 × 10 −6 , Odds Ratio = 3.6[2.0–6.4]). These hubs include genes associated with body-mass index and obesity related traits ( GNB1 , PPP1CB , RCAN2 , RSBN1 , PSD3 , TOMM20 ) 34, 35 ; anorexia nervosa ( PPP3CA ) 36 ; bipolar disorder ( MARCKS , BASP-1 ) 37, 38 ; and schizophrenia ( GPM6A ) 39 . Since the reward circuitry is central to both addictive and feeding behaviors and several hub genes were associated with BMI and obesity, we specifically tested if BMI and obesity genes were enriched in the brown module.…”

Section: Resultsmentioning

confidence: 99%

Gene Network Dysregulation in Dorsolateral Prefrontal Cortex Neurons of Humans with Cocaine Use Disorder

Ribeiro

Scarpa

Garamszegi

et al. 2017

Sci Rep

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Metabolic and functional alterations of neurons in the dorsolateral prefrontal cortex (dlPFC) are thought to contribute to impulsivity, which is a hallmark of addictive behaviors that underlie compulsive drug seeking and taking in humans. To determine if there is a transcriptional signature in dlPFC neurons of humans with cocaine use disorder, we performed total RNA-sequencing on neuronal nuclei isolated from post-mortem dlPFC of cocaine addicts and healthy controls. Our results point toward a transcriptional mechanism whereby cocaine alters specific gene networks in dlPFC neurons. In particular, we identified an AP-1 regulated transcriptional network in dlPFC neurons associated with cocaine use disorder that contains several differentially expressed hub genes. Several of these hub genes are GWAS hits for traits that might involve dysfunction of brain reward circuitry (Body-Mass Index, Obesity) or dlPFC (Bipolar disorder, Schizophrenia). Further study is warranted to determine their potential pathophysiological role in cocaine addiction.

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“…Intriguingly, alleles conferring migraine susceptibility were also associated with risk for CHD suggesting a common pathophysiology. The distal haplotype block of PHACTR1 also contains hits in the GWAS catalogue (www.genome.gov/gwastudies; accessed May 2013; [21]), originating from a 100k GWAS for femoral neck width in females of the Framingham Heart Study [43] and a linkage study for pulse pressure in 63 Chinese sib-pairs [44] (Fig. 2b).…”

Section: Chr6p241 (Phactr1): Frequently Replicated But Poorly Undersmentioning

confidence: 99%

From genotype to phenotype in human atherosclerosis - recent findings

Holdt

Teupser

2013

Current Opinion in Lipidology

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Purpose of reviewSince 2007, genome-wide association studies (GWAS) have led to the identification of numerous loci of atherosclerotic cardiovascular disease. The majority of these loci harbor genes previously not known to be involved in atherogenesis. In this review, we summarize the recent progress in understanding the pathophysiology of genetic variants in atherosclerosis.Recent findingsFifty-eight loci with P < 10−7 have been identified in GWAS for coronary heart disease and myocardial infarction. Of these, 23 loci (40%) overlap with GWAS loci of classical risk factors such as lipids, blood pressure, and diabetes mellitus, suggesting a potential causal relation. The vast majority of the remaining 35 loci (60%) are at genomic regions where the mechanism in atherogenesis is unclear. Loci most frequently found in independent GWAS were at Chr9p21.3 (ANRIL/CDKN2B-AS1), Chr6p24.1 (PHACTR1), and Chr1p13.3 (CELSR2, PSRC1, MYBPHL, SORT1). Recent work suggests that Chr9p21.3 exerts its effects through epigenetic regulation of target genes, whereas mechanisms at Chr6p24.1 remain obscure, and Chr1p13.3 affects plasma LDL cholesterol.SummaryNovel GWAS loci indicate that our understanding of atherosclerosis is limited and implicate a role of hitherto unknown mechanisms, such as epigenetic gene regulation in atherogenesis.

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Genome-wide linkage and association scans for pulse pressure in Chinese twins

Cited by 12 publications

References 38 publications

Rare Exome Sequence Variants in CLCN6 Reduce Blood Pressure Levels and Hypertension Risk

Rare Exome Sequence Variants in CLCN6 Reduce Blood Pressure Levels and Hypertension Risk

Gene Network Dysregulation in Dorsolateral Prefrontal Cortex Neurons of Humans with Cocaine Use Disorder

From genotype to phenotype in human atherosclerosis - recent findings

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