title: Obesity-related genetic variants, human pigmentation, and risk of melanoma.
abstract: Previous biological studies showed evidence of a genetic link between obesity and pigmentation in both animal models and humans. Our study investigated the individual and joint associations between obesity-related single nucleotide polymorphisms (SNPs) and both human pigmentation and risk of melanoma. Eight obesity-related SNPs in the FTO, MAP2K5, NEGR1, FLJ35779, ETV5, CADM2, and NUDT3 genes were nominally significantly associated with hair color among 5,876 individuals of European ancestry. The genetic score combining 35 independent obesity-risk loci was significantly associated with darker hair color (beta-coefficient per ten alleles = 0.12, P value = 4 × 10(-5)). However, single SNPs or genetic scores showed non-significant association with tanning ability. We further examined the SNPs at the FTO locus for their associations with pigmentation and risk of melanoma. Among the 783 SNPs in the FTO gene with imputation R (2) quality metric >0.8 using the 1,000 genome data set, ten and three independent SNPs were significantly associated with hair color and tanning ability respectively. Moreover, five independent FTO SNPs showed nominally significant association with risk of melanoma in 1,804 cases and 1,026 controls. But none of them was associated with obesity or in linkage disequilibrium with obesity-related variants. FTO locus may confer variation in human pigmentation and risk of melanoma, which may be independent of its effect on obesity.
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Liming
authors.initials: L
authors.lastname: Liang
authors.forename: Mingfeng
authors.initials: M
authors.lastname: Zhang
authors.forename: Fengju
authors.initials: F
authors.lastname: Song
authors.forename: Hongmei
authors.initials: H
authors.lastname: Nan
authors.forename: Li-E
authors.initials: LE
authors.lastname: Wang
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Lee
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.forename: Abrar A
authors.initials: AA
authors.lastname: Qureshi
authors.forename: Jiali
authors.initials: J
authors.lastname: Han
mesh_terms: D016022:Case-Control Studies; D005260:Female; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D009765:Obesity / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D010858:Pigmentation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People
references.citation: Trends Genet. 2010 Jun;26(6):266-74
references.pmid: 20381893
references.citation: Ann Hum Genet. 1964 Sep;28:27-37
references.pmid: 14204850
references.citation: Science. 2007 May 11;316(5826):889-94
references.pmid: 17434869
references.citation: Am J Phys Anthropol. 1981 Jun;55(2):203-8
references.pmid: 7258341
references.citation: Nat Genet. 2010 Nov;42(11):937-48
references.pmid: 20935630
references.citation: Int J Cancer. 2009 Aug 15;125(4):909-17
references.pmid: 19384953
references.citation: BMC Biochem. 2007 Nov 08;8:23
references.pmid: 17996046
references.citation: Am J Physiol Endocrinol Metab. 2003 Mar;284(3):E468-74
references.pmid: 12556347
references.citation: Endocr Rev. 2006 Dec;27(7):736-49
references.pmid: 17077189
references.citation: Am J Clin Nutr. 2011 Apr;93(4):851-60
references.pmid: 21248185
references.citation: PLoS Genet. 2007 Jul;3(7):e115
references.pmid: 17658951
references.citation: Annu Rev Genet. 2003;37:67-90
references.pmid: 14616056
references.citation: J Invest Dermatol. 2009 Sep;129(9):2250-7
references.pmid: 19340012
references.citation: Am J Hum Genet. 2004 Nov;75(5):739-51
references.pmid: 15372380
references.citation: Obes Res. 1996 Jan;4(1):96-100
references.pmid: 8787943
references.citation: Science. 2007 Jun 1;316(5829):1341-5
references.pmid: 17463248
references.citation: EMBO Rep. 2005 Apr;6(4):315-20
references.pmid: 15809658
references.citation: Nat Genet. 2008 Jun;40(6):768-75
references.pmid: 18454148
references.citation: J Natl Cancer Inst. 1968 Jun;40(6):1161-6
references.pmid: 4298250
references.citation: Arterioscler Thromb Vasc Biol. 2010 Feb;30(2):327-32
references.pmid: 19910641
references.citation: J Natl Cancer Inst. 1961 Apr;26:969-83
references.pmid: 13713953
references.citation: Pigment Cell Melanoma Res. 2010 Oct;23(5):587-606
references.pmid: 20546537
references.citation: Nat Genet. 2009 Jan;41(1):25-34
references.pmid: 19079261
references.citation: Science. 2007 Nov 30;318(5855):1469-72
references.pmid: 17991826
references.citation: Trends Endocrinol Metab. 2011 Feb;22(2):53-9
references.pmid: 21131211
references.citation: FASEB J. 1994 May;8(8):479-88
references.pmid: 8181666
references.citation: Pharmacol Ther. 2006 Jul;111(1):1-15
references.pmid: 16488018
references.citation: Ann N Y Acad Sci. 2003 Jun;994:267-74
references.pmid: 12851325
references.citation: J Hered. 1962 Mar-Apr;53:84-6
references.pmid: 13886198
references.citation: Nat Genet. 1998 Jun;19(2):155-7
references.pmid: 9620771
references.citation: Mol Cell. 2013 Jan 10;49(1):145-57
references.pmid: 23201126
references.citation: Nat Genet. 2009 Jan;41(1):18-24
references.pmid: 19079260