title: Analyses of shared genetic factors between asthma and obesity in children.
abstract: BACKGROUND
  Epidemiologic studies consistently show associations between asthma and obesity. Shared genetics might account for this association.
  
  
  OBJECTIVE
  We sought to identify genetic variants associated with both asthma and obesity.
  
  
  METHODS
  On the basis of a literature search, we identified genes from (1) genome-wide association studies (GWASs) of body mass index (BMI; n = 17 genes), (2) GWASs of asthma (n = 14), and (3) candidate gene studies of BMI and asthma (n = 7). We used GWAS data from the Childhood Asthma Management Program to analyze associations between single nucleotide polymorphisms (SNPs) in these genes and asthma (n = 359 subjects) and BMI (n = 537).
  
  
  RESULTS
  One top BMI GWAS SNP from the literature, rs10938397 near glucosamine-6-phosphate deaminase 2 (GNPDA2), was associated with both BMI (P = 4 x 10(-4)) and asthma (P = .03). Of the top asthma GWAS SNPs and the candidate gene SNPs, none was found to be associated with both BMI and asthma. Gene-based analyses that included all available SNPs in each gene found associations (P < .05) with both phenotypes for several genes: neuronal growth regulator 1 (NEGR1); roundabout, axon guidance receptor, homolog 1 (ROBO1); diacylglycerol kinase, gamma (DGKG); Fas apoptotic inhibitory molecule 2 (FAIM2); fat mass and obesity associated (FTO); and carbohydrate (N-acetylgalactosamine 4-0) sulfotransferase 8 (CHST8) among the BMI GWAS genes; interleukin 1 receptor-like 1 / interleukin 18 receptor 1 (IL1RL1/IL18R1), dipeptidyl-peptidase 10 (DPP10), phosphodiesterase 4D (PDE4D), V-myb myeloblastosis viral oncogene homolog (MYB), PDE10A, IL33, and especially protein tyrosine phosphatase, receptor type D (PTPRD) among the asthma GWAS genes; and protein kinase C, alpha (PRKCA) among the BMI and asthma candidate genes.
  
  
  CONCLUSIONS
  SNPs within several genes showed associations to BMI and asthma at a genetic level, but none of these associations were significant after correction for multiple testing. Our analysis of known candidate genes reveals some evidence for shared genetics between asthma and obesity, but other shared genetic determinants are likely to be identified in novel loci.
authors.affiliation: Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass 02115, USA. erik.melen@ki.se
authors.forename: Erik
authors.initials: E
authors.lastname: Melén
authors.forename: Blanca E
authors.initials: BE
authors.lastname: Himes
authors.forename: John M
authors.initials: JM
authors.lastname: Brehm
authors.forename: Nadia
authors.initials: N
authors.lastname: Boutaoui
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Klanderman
authors.forename: Jody S
authors.initials: JS
authors.lastname: Sylvia
authors.forename: Jessica
authors.initials: J
authors.lastname: Lasky-Su
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000235:genetics*; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D009765:Obesity / Q000235:genetics*; D011110:Polymorphism, Genetic
references.citation: J Allergy Clin Immunol. 2010 Feb;125(2):336-346.e4
references.pmid: 19910028
references.citation: BMC Med Genet. 2007 Sep 19;8 Suppl 1:S18
references.pmid: 17903300
references.citation: PLoS Genet. 2007 Jul;3(7):e115
references.pmid: 17658951
references.citation: Am J Respir Crit Care Med. 2009 Jun 15;179(12):1084-90
references.pmid: 19264973
references.citation: Nat Genet. 2008 Jun;40(6):768-75
references.pmid: 18454148
references.citation: JAMA. 2010 Jan 20;303(3):242-9
references.pmid: 20071470
references.citation: Nat Immunol. 2005 Jun;6(6):537-9
references.pmid: 15908930
references.citation: Obesity (Silver Spring). 2009 Dec;17(12):2254-7
references.pmid: 19478790
references.citation: Nature. 2007 Jul 26;448(7152):470-3
references.pmid: 17611496
references.citation: Control Clin Trials. 1999 Feb;20(1):91-120
references.pmid: 10027502
references.citation: Nat Genet. 2009 Jan;41(1):18-24
references.pmid: 19079260
references.citation: Int J Obes (Lond). 2010 Apr;34(4):606-13
references.pmid: 19786965
references.citation: Science. 2007 May 11;316(5826):889-94
references.pmid: 17434869
references.citation: J Asthma. 2009 Feb;46(1):53-8
references.pmid: 19191138
references.citation: Eur Respir J. 2009 May;33(5):1003-9
references.pmid: 19196817
references.citation: Best Pract Res Clin Endocrinol Metab. 2007 Dec;21(4):621-40
references.pmid: 18054739
references.citation: PLoS Genet. 2009 Aug;5(8):e1000623
references.pmid: 19714205
references.citation: Genome Res. 2008 Apr;18(4):640-3
references.pmid: 18256235
references.citation: N Engl J Med. 2010 Jan 7;362(1):36-44
references.pmid: 20032318
references.citation: Am J Hum Genet. 2009 May;84(5):581-93
references.pmid: 19426955
references.citation: Nat Genet. 2009 Jan;41(1):25-34
references.pmid: 19079261
references.citation: Am J Hum Genet. 2009 Jul;85(1):87-96
references.pmid: 19576566
references.citation: Genes Immun. 2006 Mar;7(2):95-100
references.pmid: 16395390
references.citation: Int Arch Allergy Immunol. 2005 Jul;137(3):263-4
references.pmid: 15961956
references.citation: Am J Hum Genet. 2008 Apr;82(4):849-58
references.pmid: 18387595
references.citation: Hum Mol Genet. 2008 Jun 15;17(12):1803-13
references.pmid: 18325910
references.citation: J Mol Med (Berl). 2004 Jul;82(7):459-66
references.pmid: 15150650
references.citation: Clin Exp Allergy. 2007 Apr;37(4):476-84
references.pmid: 17430342
references.citation: Obesity (Silver Spring). 2006 Apr;14(4):529-644
references.pmid: 16741264
references.citation: Eur J Hum Genet. 2008 Oct;16(10):1283-8
references.pmid: 18414509
references.citation: Nat Genet. 2009 Mar;41(3):342-7
references.pmid: 19198610
references.citation: Clin Exp Allergy. 2008 Nov;38(11):1727-37
references.pmid: 18727619
references.citation: J Allergy Clin Immunol. 2008 May;121(5):1075-84; quiz 1085-6
references.pmid: 18378287
references.citation: Am J Hum Genet. 2007 Sep;81(3):559-75
references.pmid: 17701901
references.citation: Science. 2006 Apr 14;312(5771):279-83
references.pmid: 16614226
references.citation: J Allergy Clin Immunol. 2005 Dec;116(6):1235-41
references.pmid: 16337451
references.citation: Allergy. 2007 Oct;62(10):1199-204
references.pmid: 17845591
references.citation: Int J Obes (Lond). 2007 Feb;31(2):392-3
references.pmid: 16770334
references.citation: Thorax. 2003 Dec;58(12):1036-41
references.pmid: 14645968