RESUMEN
Despite growing public awareness of the adverse consequences of excessive sun exposure, modifying sun-seeking behavior is challenging because it appears to be driven by addictive mechanisms. This can have effects on health because sun exposure, although beneficial, when prolonged and repeated shows a causal relationship with skin cancer risk. Using data from 2,500 United Kingdom twins, we observed sun seeking to be significantly heritable (h2 ≥ 58%). In a GWAS meta-analysis of sun-seeking behavior in 261,915 subjects of European ancestry, we identified five GWAS-significant loci previously associated with addiction, behavioral and personality traits, cognitive function, and educational attainment and enriched for CNS gene expression: MIR2113 (P = 2.08 × 10-11), FAM76B/MTMR2/CEP57 (P = 3.70 × 10-9), CADM2 (P = 9.36 × 10-9), TMEM182 (P = 1.64 × 10-8), and PLCL1/LINC01923/SATB2 (P = 3.93 × 10-8). These findings imply that the behavior concerning UV exposure is complicated by a genetic predisposition shared with neuropsychological traits. This should be taken into consideration when designing awareness campaigns and may help improve people's attitudes toward sun exposure.
Asunto(s)
Conducta Adictiva/genética , Enfermedades en Gemelos/genética , Predisposición Genética a la Enfermedad , Carácter Cuantitativo Heredable , Baño de Sol/psicología , Conducta Adictiva/epidemiología , Enfermedades en Gemelos/epidemiología , Estudio de Asociación del Genoma Completo , Conocimientos, Actitudes y Práctica en Salud , Humanos , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/prevención & control , Clase Social , Luz Solar/efectos adversos , Reino Unido/epidemiología , Población Blanca/genéticaRESUMEN
Body site is highly relevant for melanoma: it affects prognosis and varies according to the patient's sex. The distribution of naevi, a major risk factor for melanoma, at different body sites also varies according to sex in childhood. Using naevus counts at different body sites in 492 unrelated adults from both sexes, we observed that women have an increased number of naevi on the lower limbs compared to men (p = 8.5 × 10-5 ), showing that a high naevus count on this site persists from childhood throughout life. Then, using data from 3,232 twins, we observed, in women, the lowest naevus count heritability on the trunk (26%), and the highest on the lower limbs (69%). Finally, we showed that, in 2,864 women, six genomic loci previously associated with both naevus count and melanoma risk (IRF4, DOCK8, MTAP, 9q31.2, KITLG and PLA2G6) have an effect on naevus count that is body site-specific, but whose effect sizes are predominantly stronger on the lower limbs. Sex-specific genetic influence on naevus count at different sites may explain differences in site-specific melanoma incidence as well as prognosis between sexes.
Asunto(s)
Nevo Pigmentado/genética , Especificidad de Órganos , Femenino , Predisposición Genética a la Enfermedad , Humanos , Patrón de Herencia/genética , Masculino , Especificidad de Órganos/genética , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
The original version of this Article contained errors in the spelling of the authors Fan Liu and M. Arfan Ikram, which were incorrectly given as Fan Lui and Arfan M. Ikram. In addition, the original version of this Article also contained errors in the author affiliations which are detailed in the associated Publisher Correction.
RESUMEN
The total number of acquired melanocytic nevi on the skin is strongly correlated with melanoma risk. Here we report a meta-analysis of 11 nevus GWAS from Australia, Netherlands, UK, and USA comprising 52,506 individuals. We confirm known loci including MTAP, PLA2G6, and IRF4, and detect novel SNPs in KITLG and a region of 9q32. In a bivariate analysis combining the nevus results with a recent melanoma GWAS meta-analysis (12,874 cases, 23,203 controls), SNPs near GPRC5A, CYP1B1, PPARGC1B, HDAC4, FAM208B, DOCK8, and SYNE2 reached global significance, and other loci, including MIR146A and OBFC1, reached a suggestive level. Overall, we conclude that most nevus genes affect melanoma risk (KITLG an exception), while many melanoma risk loci do not alter nevus count. For example, variants in TERC and OBFC1 affect both traits, but other telomere length maintenance genes seem to affect melanoma risk only. Our findings implicate multiple pathways in nevogenesis.
Asunto(s)
Pleiotropía Genética/genética , Melanoma/genética , Nevo Pigmentado/genética , Neoplasias Cutáneas/genética , Población Blanca/genética , Proteínas Portadoras/genética , Citocromo P-450 CYP1B1/genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Fosfolipasas A2 Grupo VI/genética , Factores de Intercambio de Guanina Nucleótido/genética , Histona Desacetilasas/genética , Humanos , Factores Reguladores del Interferón/genética , MicroARNs/genética , Proteínas de Microfilamentos/genética , Proteínas del Tejido Nervioso/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleótido Simple , ARN/genética , Proteínas de Unión al ARN , Receptores Acoplados a Proteínas G/genética , Proteínas Represoras/genética , Factor de Células Madre/genética , Telomerasa/genética , Proteínas de Unión a Telómeros/genéticaRESUMEN
The skin's tendency to sunburn rather than tan is a major risk factor for skin cancer. Here we report a large genome-wide association study of ease of skin tanning in 176,678 subjects of European ancestry. We identify significant association with tanning ability at 20 loci. We confirm previously identified associations at six of these loci, and report 14 novel loci, of which ten have never been associated with pigmentation-related phenotypes. Our results also suggest that variants at the AHR/AGR3 locus, previously associated with cutaneous malignant melanoma the underlying mechanism of which is poorly understood, might act on disease risk through modulation of tanning ability.
Asunto(s)
Proteínas Portadoras/genética , Sitios Genéticos , Proteínas de Neoplasias/genética , Receptores de Hidrocarburo de Aril/genética , Quemadura Solar/genética , Bronceado/genética , Población Blanca/genética , Adulto , Anciano , Mapeo Cromosómico , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Color del Cabello/genética , Humanos , Masculino , Melanoma/etiología , Melanoma/genética , Persona de Mediana Edad , Neoplasias Inducidas por Radiación/genética , Fenotipo , Polimorfismo de Nucleótido Simple , Estudios Prospectivos , Exposición a la Radiación , Factores de Riesgo , Factores Sexuales , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/genética , Reino UnidoRESUMEN
To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
