Heritability and Genome-Wide Association Analyses of Serum Uric Acid in Middle and Old-Aged Chinese Twins

Wang, Weijing; Zhang, Dongfeng; Xu, Chunsheng; Wu, Yili; Duan, Haiping; Li, Shuxia; Tan, Qihua

doi:10.3389/fendo.2018.00075

Cited by 26 publications

(20 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Genetic heritability of serum urate varies between 30% and 60% in diverse populations [6][7][8][9][10][11] . Candidate gene and early genome-wide associations studies (GWAS) have identified three genes as major determinants of urate levels: SLC2A9, ABCG2, and SLC22A12 7,[12][13][14][15][16][17][18] .…”

Section: Introductionmentioning

confidence: 99%

Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels

Tin¹,

Marten²,

Kuhns³

et al. 2019

Nat Genet

312

317

View full text Add to dashboard Cite

Elevated serum urate levels cause gout, and correlate with cardio-metabolic diseases via poorly understood mechanisms. We performed a trans-ethnic genome-wide association study of serum urate among 457,690 individuals, identifying 183 loci (147 novel) that improve prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardio-metabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urateassociated loci and co-localization with gene expression in 47 tissues implicated kidney and liver as main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A trans-activated the promoter of the major urate transporter ABCG2 in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardio-metabolic traits.

show abstract

Section: Introductionmentioning

confidence: 99%

Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels

Tin¹,

Marten²,

Kuhns³

et al. 2019

Nat Genet

312

317

View full text Add to dashboard Cite

show abstract

“…Although the risk factors for hyperuricemia have not been fully determined, recent studies have shown that apart from genetic variations [ 26 ], several lifestyle or dietary factors have been associated with hyperuricemia. As uric acid is an ultimate product of purine metabolism, hyperuricemia is related to the intake of purine-rich food.…”

Section: Introductionmentioning

confidence: 99%

The Association between Purine-Rich Food Intake and Hyperuricemia: A Cross-Sectional Study in Chinese Adult Residents

Aihemaitijiang

Zhang

et al. 2020

Nutrients

View full text Add to dashboard Cite

Objective: To explore the correlation between purine-rich food intake and hyperuricemia in Chinese adult residents. Method: A cross-sectional study was conducted on the purine-rich food intake of Chinese adult residents based on the China Health and Nutrition Survey (CHNS) in 2009. The subjects were divided into hyperuricemia group and nonhyperuricemia group according to serum uric acid level, and the differences of the sociodemographic information (age, gender, and region), health status (weight status, blood pressure, blood sugar status), living habits (alcohol consumption, smoking status) and food intake (purine-rich food, other food) were compared between the two groups. Logistic regressions investigated the associations between the daily intake of purine-rich food (animal-derived food and legumes) and hyperuricemia. Results: Eventually, 6813 subjects were included in our study, 1111 of them had hyperuricemia. The intake of seafood, legumes, red meat, and poultry all increased the risk of hyperuricemia (p < 0.05), while the intake of purine-rich fungi and purine-rich vegetables did not affect the occurrence of hyperuricemia. Animal-derived food was the main source of purine-rich food consumed by Chinese adult residents (140.67g/day), which had a great impact on hyperuricemia. Finally, after adjusting for gender, age, region, body mass index (BMI), alcohol consumption, hypertension, and refined grains intake, the risk of hyperuricemia increased by 2.40% and 1.10% for each increase of 10 g in animal-derived food intake (OR = 1.024, 95% CI: 1.018–1.030) and legumes intake (OR = 1.011, 95% CI: 1.003–1.019), respectively. Conclusion: The intake of animal-derived food and legumes were positively correlated with the occurrence of hyperuricemia. Controlling the intake of animal-derived food and legumes would be more beneficial to controlling the risk of hyperuricemia.

show abstract

“…Twin samples will have a higher power in genetic study, especially in human complex diseases ( 21 ). Here based on 382 Chinese twin pairs, we explored the genetic effect on TC, HDL-C, LDL-C variation and further searched for genetic susceptibility loci for these traits using GWAS ( 22 ).…”

Section: Introductionmentioning

confidence: 99%

Heritability and Genome-Wide Association Study of Plasma Cholesterol in Chinese Adult Twins

et al. 2018

Self Cite

View full text Add to dashboard Cite

Dyslipidemia represents a strong and independent risk factor for cardiovascular disease. Plasma cholesterol, such as total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C), is the common indicator of diagnosing dyslipidemia. Here based on 382 Chinese twin pairs, we explored the magnitude of genetic impact on TC, HDL-C, LDL-C variation and further searched for genetic susceptibility loci for them using genome-wide association study (GWAS). The ACE model was the best fit model with additive genetic parameter (A) accounting for 26.6%, common or shared environmental parameter (C) accounting for 47.8%, unique/non-shared environmental parameter (E) accounting for 25.6% for the variance in HDL-C. The AE model was the best fit model for TC (A: 61.4%; E: 38.6%) and LDL-C (A: 65.5%; E: 34.5%). While no SNPs reached the genome-wide significance level (P < 5 × 10−8), 8, 14, 9 SNPs exceeded the suggestive significance level (P < 1 × 10−5) for TC, HDL-C, LDL-C, respectively. The promising genetic regions for TC, HDL-C, LDL-C were on chromosome 11 around rs7107698, chromosome 5 around rs12518218, chromosome 2 around rs10490120, respectively. Gene-based analysis found 1038, 1033 and 1090 genes nominally associated with TC, HDL-C, LDL-C (P < 0.05), especially FAF1, KLKB1 for TC, KLKB1 for HDL-C, and NTRK1, FAF1, SNTB2 for LDL-C, respectively. The number of common related genes among TC, HDL-C and LDL-C was 71, including FAF1, KLKB1, etc. Pathway enrichment analysis discovered known related pathways-zinc transporters, metal ion SLC transporters for TC, cell adhesion molecules CAMs, IL-6 signaling for HDL, FC epsilon RI signaling pathway, NFAT pathway for LDL, respectively. In conclusion, the TC and LDL-C level is moderately heritable and the HDL-C level is lowly heritable in Chinese population. The genomic loci, functional genes and pathways are identified to account for the heritability of plasma cholesterol level. Our findings provide important insights into plasma cholesterol molecular physiology and expect future research to replicate and validate our results.

show abstract

Heritability and Genome-Wide Association Analyses of Serum Uric Acid in Middle and Old-Aged Chinese Twins

Cited by 26 publications

References 59 publications

Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels

Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels

The Association between Purine-Rich Food Intake and Hyperuricemia: A Cross-Sectional Study in Chinese Adult Residents

Heritability and Genome-Wide Association Study of Plasma Cholesterol in Chinese Adult Twins

Contact Info

Product

Resources

About