Genetic variants in vitamin D metabolism-related genes and body mass index: analysis of genome-wide scan data of approximately 7000 Chinese women

SummaryThrombosis and obesity are complex epidemiologically associated diseases. The mechanism of this association is not yet understood. It was the objective of this study to identify genetic components of body mass index (BMI) and their possible role in the risk of thromboembolic disease. With the self-reported BMI of 397 individuals from 21 extended families enrolled in the GAIT (Genetic Analysis of Idiopathic Thrombophilia) Project, we estimated the heritability of BMI and the genetic correlation with the risk of thrombosis. Subjects were genotyped for an autosomal genome-wide scan with 363 highly-informative DNA markers. Univariate and bivariate multipoint linkage analyses were performed. The heritability for BMI was 0.31 (p= 2.9×10–5). Thromboembolic disease (including venous and arterial) and BMI had a significant genetic correlation (ρG= 0.54, p= 0.005). Two linkage signals for BMI were obtained, one at 13q34 (LOD= 3.36, p= 0.0004) and other at 2q34, highly suggestive of linkage (LOD= 1.95). Bivariate linkage analysis with BMI and thrombosis risk also showed a significant signal at 13q34 (LOD= 3), indicating that this locus influences at the same time normal variation in the BMI phenotype as well as susceptibility to thrombosis. In conclusion, BMI and thrombosis are genetically correlated. The locus 13q34, which showed pleiotropy with both phenotypes, contains two candidate genes, which may explain our linkage pleiotropic signal and deserve further investigation as possible risk factors for obesity and thrombosis.

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Common Genetic Variants in the Vitamin D Pathway Including Genome-Wide Associated Variants Are Not Associated with Breast Cancer Risk among Chinese Women

Cancer Epidemiology Biomarkers & Prevention ◽

10.1158/1055-9965.epi-11-0704 ◽

2011 ◽

Vol 20 (10) ◽

pp. 2313-2316 ◽

Cited By ~ 24

Author(s):

Tsogzolmaa Dorjgochoo ◽

Ryan Delahanty ◽

Wei Lu ◽

Jirong Long ◽

Qiuyin Cai ◽

...

Keyword(s):

Breast Cancer ◽

Vitamin D ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Genetic Variants ◽

Chinese Women ◽

Genome Wide ◽

Common Genetic Variants

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Genetic Variants Associated with Circulating Fibroblast Growth Factor 23

Journal of the American Society of Nephrology ◽

10.1681/asn.2018020192 ◽

2018 ◽

Vol 29 (10) ◽

pp. 2583-2592 ◽

Cited By ~ 12

Author(s):

Cassianne Robinson-Cohen ◽

Traci M. Bartz ◽

Dongbing Lai ◽

T. Alp Ikizler ◽

Munro Peacock ◽

...

Keyword(s):

Vitamin D ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Genetic Variants ◽

Fibroblast Growth Factor 23 ◽

Phosphate Transport ◽

Fibroblast Growth ◽

Vitamin D Metabolism ◽

Genome Wide ◽

Fgf23 Concentration

BackgroundFibroblast growth factor 23 (FGF23), a bone-derived hormone that regulates phosphorus and vitamin D metabolism, contributes to the pathogenesis of mineral and bone disorders in CKD and is an emerging cardiovascular risk factor. Central elements of FGF23 regulation remain incompletely understood; genetic variation may help explain interindividual differences.MethodsWe performed a meta-analysis of genome-wide association studies of circulating FGF23 concentrations among 16,624 participants of European ancestry from seven cohort studies, excluding participants with eGFR<30 ml/min per 1.73 m2 to focus on FGF23 under normal conditions. We evaluated the association of single-nucleotide polymorphisms (SNPs) with natural log–transformed FGF23 concentration, adjusted for age, sex, study site, and principal components of ancestry. A second model additionally adjusted for BMI and eGFR.ResultsWe discovered 154 SNPs from five independent regions associated with FGF23 concentration. The SNP with the strongest association, rs17216707 (P=3.0×10−24), lies upstream of CYP24A1, which encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D. Each additional copy of the T allele at this locus is associated with 5% higher FGF23 concentration. Another locus strongly associated with variations in FGF23 concentration is rs11741640, within RGS14 and upstream of SLC34A1 (a gene involved in renal phosphate transport). Additional adjustment for BMI and eGFR did not materially alter the magnitude of these associations. Another top locus (within ABO, the ABO blood group transferase gene) was no longer statistically significant at the genome-wide level.ConclusionsCommon genetic variants located near genes involved in vitamin D metabolism and renal phosphate transport are associated with differences in circulating FGF23 concentrations.

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Evaluation of the genetic overlap between osteoarthritis with body mass index and height using genome-wide association scan data

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2012-202081 ◽

2012 ◽

Vol 72 (6) ◽

pp. 935-941 ◽

Cited By ~ 30

Author(s):

Katherine S Elliott ◽

Kay Chapman ◽

Aaron Day-Williams ◽

Kalliope Panoutsopoulou ◽

Lorraine Southam ◽

...

Keyword(s):

Body Mass Index ◽

Body Mass ◽

Genome Wide Association ◽

Genome Wide ◽

Genetic Overlap ◽

Scan Data

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Genome-Wide Scan of Obesity in Finnish Sibpairs Reveals Linkage to Chromosome Xq24*

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.85.9.6797 ◽

2000 ◽

Vol 85 (9) ◽

pp. 3183-3190 ◽

Cited By ~ 1

Author(s):

Miina Öhman ◽

Laura Oksanen ◽

Jaakko Kaprio ◽

Markku Koskenvuo ◽

Pertti Mustajoki ◽

...

Keyword(s):

Body Mass Index ◽

Body Mass ◽

Chromosomal Region ◽

Adult Population ◽

Average Density ◽

Model Free ◽

Melanocortin 4 Receptor ◽

Genome Wide ◽

Sample Set ◽

Genome Wide Scan

Abstract Obesity is a multifactorial trait with evidence of a genetic component. Obesity is very common in all westernized countries, including Finland, where 10% of the adult population has a body mass index of 32 kg/m2 or more. Here we report results from a three-stage genome-wide scan of obesity in 188 affected subjects (body mass index,≥ 32 kg/m2) from 87 Finnish families. Initially, 374 markers with an average density of 10 centimorgans were genotyped. The strongest evidence for linkage to obesity was detected on chromosome Xq24, with the marker DXS6804 providing a maximum likelihood score (MLS) 3.14 in a model-free 2-point sibpair analysis. Fine-mapping in an extended sample set of 367 affected subjects from 166 families yielded a multipoint MLS of 3.48 over this X-chromosomal region. The Xq24 region contains a plausible candidate gene, serotonin 2C receptor, variants of which have been shown to predispose to obesity and type II diabetes in mice. Another chromosomal region also provided suggestive evidence of linkage, an area on 18q21, flanking the melanocortin-4 receptor, where a 2-point MLS of 2.42 with marker D18S1155 was obtained with a set of 367 affected subjects. In conclusion, our results in this Finnish study sample suggest that a locus on chromosome Xq24 influences the risk of obesity.

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Replication of Interactions between Genome-Wide Genetic Variants and Body Mass Index in Fasting Glucose and Insulin Levels

Genomics & Informatics ◽

10.5808/gi.2014.12.4.236 ◽

2014 ◽

Vol 12 (4) ◽

pp. 236

Author(s):

Kyung-Won Hong ◽

Myungguen Chung ◽

Seong Beom Cho

Keyword(s):

Body Mass Index ◽

Body Mass ◽

Genetic Variants ◽

Fasting Glucose ◽

Insulin Levels ◽

Genome Wide

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A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

Nature Genetics ◽

10.1038/ng.2274 ◽

2012 ◽

Vol 44 (6) ◽

pp. 659-669 ◽

Cited By ~ 519

Author(s):

Alisa K Manning ◽

◽

Marie-France Hivert ◽

Robert A Scott ◽

Jonna L Grimsby ◽

...

Keyword(s):

Insulin Resistance ◽

Body Mass Index ◽

Body Mass ◽

Genetic Variants ◽

Genome Wide ◽

A Genome

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Further Evidence for a QTL Influencing Body Mass Index on Chromosome 7p from a Genome-wide Scan in Dutch Families

Twin Research ◽

10.1375/136905204323016177 ◽

2004 ◽

Vol 7 (2) ◽

pp. 192-196 ◽

Cited By ~ 13

Author(s):

Bastiaan T. Heijmans ◽

A. Leo Beem ◽

Gonneke Willemsen ◽

Daniëlle Posthuma ◽

P. Eline Slagboom ◽

...

Keyword(s):

Body Mass Index ◽

Body Mass ◽

Genome Wide ◽

A Genome ◽

Genome Wide Scan

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Bivariate genome-wide association study (GWAS) of body mass index and blood pressure phenotypes in northern Chinese twins

PLoS ONE ◽

10.1371/journal.pone.0246436 ◽

2021 ◽

Vol 16 (2) ◽

pp. e0246436

Author(s):

Zhaoying Li ◽

Weijing Wang ◽

Xiaocao Tian ◽

Haiping Duan ◽

Chunsheng Xu ◽

...

Keyword(s):

Blood Pressure ◽

Body Mass Index ◽

Body Mass ◽

Genetic Variants ◽

Quantitative Trait ◽

Association Studies ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Genome Wide ◽

Northern Chinese

Recently, new loci related to body mass index (BMI) or blood pressure (BP) have been identified respectively in genome-wide association studies (GWAS). However, limited studies focused on jointly associated genetic variance between systolic pressure (SBP), diastolic pressure (DBP) and BMI. Therefore, a bivariate twin study was performed to explore the genetic variants associated with BMI-SBP, BMI-DBP and SBP-DBP. A total of 380 twin pairs (137 dizygotic pairs and 243 monozygotic pairs) recruited from Qingdao Twin Registry system were used to access the genetic correlations (0.2108 for BMI-SBP, 0.2345 for BMI-DBP, and 0.6942 for SBP-DBP, respectively) by bivariate Cholesky decomposition model. Bivariate GWAS in 137 dizygotic pairs nominated 27 single identified 27 quantitative trait nucleotides (QTNs) for BMI and SBP, 27 QTNs for BMI and DBP, and 25 QTNs for SBP and DBP with the suggestive P-value threshold of 1×10−5. After imputation, we found eight SNPs, one for both BMI-SBP and SBP-DBP, and eight for SBP-DBP, exceed significant statistic level. Expression quantitative trait loci analysis identified rs4794029 as new significant eQTL in tissues related to BMI and SBP. Also, we found 6 new significant eQTLs (rs4400367, rs10113750, rs11776003, rs3739327, rs55978930, and rs4794029) in tissues were related to SBP and DBP. Gene-based analysis identified nominally associated genes (P < 0.05) with BMI-SBP, BMI-DBP, and SBP-DBP, respectively, such as PHOSPHO1, GNGT2, KEAP1, and S1PR5. In the pathway analysis, we found some pathways associated with BMI-SBP, BMI-DBP and SBP-DBP, such as prion diseases, IL5 pathway, cyclin E associated events during G1/S transition, TGF beta signaling pathway, G βγ signaling through PI3Kγ, prolactin receptor signaling etc. These findings may enrich the results of genetic variants related to BMI and BP traits, and provide some evidences to future study the pathogenesis of hypertension and obesity in the northern Chinese population.

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