title: Genetic association analysis of vitamin D pathway with obesity traits.
abstract: OBJECTIVE
  Observational studies have examined the link between vitamin D deficiency and obesity traits. Some studies have reported associations between vitamin D pathway genes such as VDR, GC and CYP27B1 with body mass index (BMI) and waist circumference (WC); however, the findings have been inconsistent. Therefore, we investigated the involvement of vitamin D metabolic pathway genes in obesity-related traits in a large population-based study.
  
  
  METHODS
  We undertook a comprehensive analysis between 100 tagging single nucleotide polymorphisms (tagSNPs) in genes encoding for DHCR7, CYP2R1, VDBP, CYP27B1, CYP27A1, CYP24A1, VDR and RXRG, and obesity traits in 5224 participants (aged 45 years) in the 1958 British birth cohort (1958BC). We further extended our analyses to investigate the associations between SNPs and obesity traits using the summary statistics from the GIANT (Genetic Investigation of Anthropometric Traits) consortium (n=123 865).
  
  
  RESULTS
  In the 1958BC (n=5224), after Bonferroni correction, none of the tagSNPs were associated with obesity traits except for one tagSNP from CYP24A1 that was associated with waist-hip ratio (WHR) (rs2296239, P=0.001). However, the CYP24A1 SNP was not associated with BMI-adjusted WHR (WHRadj) in the 1958BC (rs2296239, P=1.00) and GIANT results (n=123 865, P=0.18). There was also no evidence for an interaction between the tagSNPs and obesity on BMI, WC, WHR and WHRadj in the 1958BC. In the GIANT consortium, none of the tagSNPs were associated with obesity traits.
  
  
  CONCLUSIONS
  Despite a very large study, our findings suggest that the vitamin D pathway genes are unlikely to have a major role in obesity-related traits in the general population.
authors: Centre for Paediatric Epidemiology and Biostatistics, MRC Centre of Epidemiology for Child Health, UCL Institute of Child Health, London, UK.
authors: K S
authors: KS
authors: Vimaleswaran
authors: A
authors: A
authors: Cavadino
authors: D J
authors: DJ
authors: Berry
authors: J C
authors: JC
authors: Whittaker
authors: C
authors: C
authors: Power
authors: M-R
authors: MR
authors: Järvelin
authors: E
authors: E
authors: Hyppönen
mesh_terms: D015992:Body Mass Index; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D006113:United Kingdom / Q000453:epidemiology; D014808:Vitamin D Deficiency / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D044465:White People / Q000235:genetics*
references: BMC Public Health. 2008 Jun 05;8:200
references: 18533989
references: Gynecol Endocrinol. 2008 Sep;24(9):514-8
references: 18958772
references: J Clin Endocrinol Metab. 2000 May;85(5):1951-3
references: 10843180
references: Int J Epidemiol. 2006 Feb;35(1):34-41
references: 16155052
references: PLoS Genet. 2009 Jun;5(6):e1000508
references: 19557161
references: PLoS One. 2012;7(5):e37465
references: 22629401
references: Int J Obes (Lond). 2012 Sep;36(9):1252-5
references: 22158264
references: Aging Male. 2008 Sep;11(3):134-9
references: 18821289
references: Nature. 2007 Jun 7;447(7145):661-78
references: 17554300
references: Eur J Endocrinol. 2001 Aug;145(2):181-6
references: 11454514
references: J Epidemiol Community Health. 2008 Mar;62(3):216-23
references: 18272736
references: Endocrinology. 2009 Feb;150(2):651-61
references: 18845643
references: Int J Obes (Lond). 2007 Aug;31(8):1319-24
references: 17342072
references: World Health Organ Tech Rep Ser. 2000;894:i-xii, 1-253
references: 11234459
references: Lancet. 2003 Feb 15;361(9357):567-71
references: 12598142
references: Int J Obes (Lond). 2012 Mar;36(3):387-96
references: 21694701
references: JAMA. 2010 Jan 20;303(3):235-41
references: 20071471
references: Int J Epidemiol. 2004 Feb;33(1):30-42
references: 15075143
references: Respir Res. 2009 Oct 24;10:98
references: 19852851
references: Nat Genet. 2009 Jun;41(6):703-7
references: 19430480
references: Int J Epidemiol. 2007 Jun;36(3):532-9
references: 17255345
references: Calcif Tissue Int. 1995 Aug;57(2):161-2
references: 7584878
references: Genet Med. 2002 Mar-Apr;4(2):45-61
references: 11882781
references: Nat Genet. 2010 Nov;42(11):937-48
references: 20935630
references: Curr Opin Nephrol Hypertens. 2011 Jul;20(4):331-6
references: 21654390
references: Carcinogenesis. 2008 Sep;29(9):1788-93
references: 18628249
references: Am J Clin Nutr. 2008 Apr;87(4):1080S-6S
references: 18400738
references: Med Hypotheses. 2009 Mar;72(3):314-21
references: 19054627
references: Bioinformatics. 2005 Jan 15;21(2):263-5
references: 15297300
references: Am J Clin Nutr. 2011 Jan;93(1):5-10
references: 21048058
references: Lancet. 2010 Jul 17;376(9736):180-8
references: 20541252
references: Diabetes Metab. 2003 Apr;29(2 Pt 1):119-24
references: 12746631