ORCID Profile
0000-0003-1141-4471
Current Organisation
University of Nottingham
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Publisher: BMJ
Date: 06-08-2013
Publisher: Elsevier BV
Date: 06-2023
Publisher: BMJ
Date: 29-08-2013
Publisher: Springer Science and Business Media LLC
Date: 25-04-2010
DOI: 10.1038/NG.573
Publisher: Springer Science and Business Media LLC
Date: 29-06-2017
DOI: 10.1038/S41598-017-03054-8
Abstract: Obesity is a genetically heterogeneous disorder. Using targeted and whole-exome sequencing, we studied 32 human and 87 rodent obesity genes in 2,548 severely obese children and 1,117 controls. We identified 52 variants contributing to obesity in 2% of cases including multiple novel variants in GNAS , which were sometimes found with accelerated growth rather than short stature as described previously. Nominally significant associations were found for rare functional variants in BBS1 , BBS9 , GNAS , MKKS , CLOCK and ANGPTL6 . The p.S284X variant in ANGPTL6 drives the association signal (rs201622589, MAF~0.1%, odds ratio = 10.13, p-value = 0.042) and results in complete loss of secretion in cells. Further analysis including additional case-control studies and population controls (N = 260,642) did not support association of this variant with obesity (odds ratio = 2.34, p-value = 2.59 × 10 −3 ), highlighting the challenges of testing rare variant associations and the need for very large s le sizes. Further validation in cohorts with severe obesity and engineering the variants in model organisms will be needed to explore whether human variants in ANGPTL6 and other genes that lead to obesity when deleted in mice, do contribute to obesity. Such studies may yield druggable targets for weight loss therapies.
Publisher: BMJ
Date: 25-05-2011
Publisher: Cambridge University Press (CUP)
Date: 20-06-2014
DOI: 10.1017/THG.2014.34
Abstract: Low weight at birth has previously been shown to be associated with a number of adult diseases such as type 2 diabetes, cardiovascular disease, high blood pressure, and obesity later in life. Genome-wide association studies (GWAS) have been published for singleton-born in iduals, but the role of genetic variation in birth weight (BW) in twins has not yet been fully investigated. A GWAS was performed in 4,593 female study participants with BW data available from the TwinsUK cohort. A genome-wide significant signal was found in chromosome 9, close to the NTRK2 gene (OMIM: 600456). QIMR, an Australian twin cohort ( n = 3,003), and UK-based singleton-birth in iduals from the Hertfordshire cohort ( n = 2,997) were used as replication for the top two single nucleotide polymorphism (SNPs) underpinning this signal, rs12340987 and rs7849941. The top SNP, rs12340987, was found to be in the same direction in the Australian twins and in the singleton-born females (fixed effects meta-analysis beta = -0.13, SE = 0.02, and p = 1.48 × 10 −8 ) but not in the singleton-born males tested. These findings provide an important insight into the genetic component of BW in twins who are normally excluded due to their lower BW when compared with singleton births, as well as the difference in BW between twins. The NTRK2 gene identified in this study has previously been associated with obesity.
Publisher: Oxford University Press (OUP)
Date: 09-01-2012
DOI: 10.1093/IJE/DYR207
Publisher: Springer Science and Business Media LLC
Date: 16-04-2018
Publisher: BMJ
Date: 08-06-2009
Publisher: Elsevier BV
Date: 06-2008
Publisher: Elsevier BV
Date: 05-2008
Publisher: Springer Science and Business Media LLC
Date: 06-03-2015
DOI: 10.1038/NCOMMS6681
Abstract: Normal thyroid function is essential for health, but its genetic architecture remains poorly understood. Here, for the heritable thyroid traits thyrotropin (TSH) and free thyroxine (FT4), we analyse whole-genome sequence data from the UK10K project ( N =2,287). Using additional whole-genome sequence and deeply imputed data sets, we report meta-analysis results for common variants (MAF≥1%) associated with TSH and FT4 ( N =16,335). For TSH, we identify a novel variant in SYN2 (MAF=23.5%, P =6.15 × 10 −9 ) and a new independent variant in PDE8B (MAF=10.4%, P =5.94 × 10 −14 ). For FT4, we report a low-frequency variant near B4GALT6/SLC25A52 (MAF=3.2%, P =1.27 × 10 −9 ) tagging a rare TTR variant (MAF=0.4%, P =2.14 × 10 −11 ). All common variants explain ≥20% of the variance in TSH and FT4. Analysis of rare variants (MAF %) using sequence kernel association testing reveals a novel association with FT4 in NRG1. Our results demonstrate that increased coverage in whole-genome sequence association studies identifies novel variants associated with thyroid function.
Publisher: BMJ
Date: 13-07-2013
Publisher: Springer Science and Business Media LLC
Date: 14-09-2015
DOI: 10.1038/NATURE14962
Publisher: Oxford University Press (OUP)
Date: 29-06-2013
DOI: 10.1093/IJE/DYT094
Publisher: Springer Science and Business Media LLC
Date: 11-05-2014
DOI: 10.1038/NG.2982
Publisher: MDPI AG
Date: 10-12-2014
DOI: 10.3390/MD12125960
Publisher: Springer Science and Business Media LLC
Date: 05-06-2015
DOI: 10.1038/NCOMMS8074
Abstract: The analysis of in iduals with ciliary chondrodysplasias can shed light on sensitive mechanisms controlling ciliogenesis and cell signalling that are essential to embryonic development and survival. Here we identify TCTEX1D2 mutations causing Jeune asphyxiating thoracic dystrophy with partially penetrant inheritance. Loss of TCTEX1D2 impairs retrograde intraflagellar transport (IFT) in humans and the protist Chlamydomonas , accompanied by destabilization of the retrograde IFT dynein motor. We thus define TCTEX1D2 as an integral component of the evolutionarily conserved retrograde IFT machinery. In complex with several IFT dynein light chains, it is required for correct vertebrate skeletal formation but may be functionally redundant under certain conditions.
Publisher: Springer Science and Business Media LLC
Date: 17-01-2018
DOI: 10.1038/S41467-017-02662-2
Abstract: Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci ( GC, NADSYN1/DHCR7, CYP2R1, CYP24A1 ). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery s le size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants ( P = 4.7×10 −9 at rs8018720 in SEC23A , and P = 1.9×10 −14 at rs10745742 in AMDHD1 ). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene–gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.
Publisher: Elsevier BV
Date: 11-2013
Publisher: American Association for the Advancement of Science (AAAS)
Date: 12-03-2021
Abstract: A GWAS including 192,986 European and 1636 Asian participants identifies 50 novel discrete associations with eye color.
Publisher: Public Library of Science (PLoS)
Date: 31-12-2013
Publisher: Wiley
Date: 11-05-2017
DOI: 10.1002/EJP.1027
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2005
DOI: 10.1097/01.BRS.0000184369.79744.A5
Abstract: A candidate gene association study in a longitudinal cohort. To investigate the association between polymorphisms at 25 candidate genes and progression of in idual radiographic features of lumbar disc degeneration (LDD). LDD is characterized radiographically by the presence of osteophytes and disc space narrowing and is known to have a genetic component. Because of the high prevalence of radiographic features, progression may be a more useful phenotype clinically to study than prevalence itself. We tested the effect on radiographic progression of LDD of polymorphisms in 25 genes, 24 of which had been previously tested with regards to knee osteoarthritis. The progression traits used were the change in radiographic grade over 9 years in osteophytes, disc space narrowing, and summary Kellgren-Lawrence grade. Lumbar spine radiographs (L1-L5) at baseline and at follow-up were read for 720 women genotyped at the 25 genes participating in the Chingford study. Polymorphisms in MMP3, TIMP1, and COX2, which encode molecules involved in inflammatory pathways, were associated with radiographic progression of LDD. The strongest associations observed (statistically significant after correcting for multiple comparisons) were between COX2 and change in osteophyte grade (P < 0.001) and Kellgren-Lawrence grade (P < 2 x 10(-5)), and between the genes for vitamin D receptor (P < 0.002) and a thrombospondin (THSD2) (P < 0.002) and change in osteophyte grade. Our results suggest a role for genes regulating inflammatory pathways in the radiographic progression of spine degeneration. This could prove a fruitful area for future therapeutics for the spine and other joints.
Location: United States of America
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Ana M. Valdes.