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Obesity-related genetic variants, human pigmentation, and risk of melanoma |
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| Authors: | Xin Li Liming Liang Mingfeng Zhang Fengju Song Hongmei Nan Li-E Wang Qingyi Wei Jeffrey E. Lee Christopher I. Amos Abrar A. Qureshi Jiali Han |
| Affiliation: | 1. Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA 2. Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA 3. Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA 4. Department of Epidemiology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China 5. Division of Cancer Epidemiology, Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA 6. Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 7. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 8. Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA 9. Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, 02115, USA |
| 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. |
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