Genome-wide association meta-analysis of individuals of European ancestry identifies new loci explaining a substantial fraction of hair color variation and heritability

Hysi, Pirro G.; Valdes, Ana M.; Liu, Fan; Furlotte, Nicholas A.; Evans, David M.; Bataille, Véronique; Visconti, Alessia; Hemani, Gibran; McMahon, George; Ring, Susan M.; Smith, George Davey; Duffy, David L.; Zhu, Gu; Gordon, Scott D.; Medland, Sarah E.; Lin, Bochao; Willemsen, Gonneke; Hottenga, Jouke Jan; Vuckovic, Dragana; Girotto, Giorgia; Gandin, Ilaria; Sala, Cinzia; Concas, Maria Pina; Brumat, Marco; Gasparini, Paolo; Toniolo, Daniela; Cocca, Massimiliano; Robino, Antonietta; Yazar, Seyhan; Hewitt, Alex W.; Chen, Yan; Zeng, Changqing; Uitterlinden, André G.; Ikram, M. Arfan; Hamer, Merel A.; Duijn, Cornelia M. van; Nijsten, Tamar; Mackey, David A.; Falchi, Mario; Boomsma, Dorret I.; Martin, Nicholas G.; Hinds, David A.; Kayser, Manfred; Spector, Timothy D.

doi:10.1038/s41588-018-0100-5

Cited by 91 publications

(108 citation statements)

References 48 publications

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“…With respect to hair color, a prediction model was developed, based on 45 single nucleotide polymorphisms (SNPs) from 12 genes, including SLC45A2 , IRF4 , EXOC2 , TYRP1 , TPCN2 , TYR , KITLG , SLC24A4 , OCA2 , HERC2 , MC1R and ASIP (Branicki et al, ). However, a recent GWAS including 300,000 participants revealed that 124 gene loci were indeed associated with hair color variation and heritability (Hysi et al, ). Among these loci, all but 13 were novel and, collectively, they could explain 34.6% of red hair, 24.8% of blond hair, and 26.1% of black hair heritability.…”

Section: The Genetic Basis Of Hair Form and The Utility Of Admixture mentioning

confidence: 99%

The biology of human hair: A multidisciplinary review

Koch

Tridico²,

Bernard

et al. 2019

American J Hum Biol

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In the last century, human scalp hair morphology has been studied from multiple, and sometimes mutually exclusive, perspectives by anthropologists, biologists, geneticists, forensic scientists, and cosmetic scientists. Here, we review and synthesize historical and current research on hair to better understand the scientific basis and biological implications of hair microstructure and morphology. We revisit the origins of existing nomenclature regarding hair morphology and classifications, discuss the currently recognized limitations to hair analysis within the varied scientific disciplines studying hair, point out aspects of hair biology that remain unknown, and the great potential for integrating these diverse perspectives and expertise in future scientific investigations, while highlighting the benefits of combining nondestructive microscopical analysis with chemical and genomic analyses for explicating hair biology. Further, we propose consensus terminology for root growth stages through descriptions and images that will aid in the morphological and microscopical analysis of human scalp hair, thereby reducing confusion and the promulgation of inaccurate information that is presently in the literature.

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Section: The Genetic Basis Of Hair Form and The Utility Of Admixture mentioning

confidence: 99%

The biology of human hair: A multidisciplinary review

Koch

Tridico²,

Bernard

et al. 2019

American J Hum Biol

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“…Non-genetic observational studies have consistently reported darkening of hair and skin pigmentation in children of European ancestry during the peri-pubertal years 17,18 . Furthermore, the established sexual dimorphism in pigmentation 16 reportedly appears from puberty onwards 17 and the relatively darker skin and hair of men compared to women is postulated to reflect the stronger stimulation of melanogenesis by androgens compared to estrogens 21 . Our findings suggest a more widespread overlap between pigmentation and reproduction, possibly reflecting common regulators of pituitary production of melanocortins and gonadotrophins, or even an impact of melanocyte signalling on puberty timing.…”

Section: Discussionmentioning

confidence: 99%

“…Noting that three novel loci for puberty timing were located proximal to genes previously associated with pigmentation (HERC2, IRF4, C16orf55), we assessed the broader relationship between these traits. It is known that men have darker natural hair colour than women in European ancestry populations 16 and this sex difference appears following the progressive darkening of hair and skin colour during adolescence 17,18 . However, a link between interindividual variation in natural hair colour and puberty timing has not previously been described.…”

Section: Genetic and Phenotypic Links Between Hair Colour And Pubertymentioning

confidence: 99%

“…To explore the genetic links between these two phenotypes, we systematically assessed the effects of genetic variants associated with natural hair colour on puberty timing. Using a twosample Mendelian randomization (MR) approach, we modelled 119 recently reported GWAS hair colour signals as a single instrumental variable 16 Figure 3). Using a similar approach in published AAM data in females 5 , we inferred a directionally consistent but weaker effect of darker natural hair colour on earlier AAM (βIVW= -0.017, PIVW=3.64×10 -3 ), and with modest heterogeneity across signals (Cochrane Q: P=0.038) ( Supplementary Table 12).…”

Section: Genetic and Phenotypic Links Between Hair Colour And Pubertymentioning

confidence: 99%

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Expanded genomic analyses for male voice-breaking highlights a shared phenotypic and genetic basis between puberty timing and hair colour

Hollis

et al. 2018

Preprint

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The timing of puberty is highly variable and has important consequences for long-term health.Most of our understanding of the genetic control of puberty timing is based on studies in women, as age at menarche is often recorded. Here, we report a multi-trait genome-wide association study for male puberty timing, based on recalled timing of voice breaking and facial hair, with an effective sample size of 205,354 men, nearly four-fold larger than previously reported. We identify 78 independent signals for male puberty timing, including 29 signals not previously associated with puberty in either sex. Novel mechanisms include an unexpected phenotypic and genetic link between puberty timing and natural hair colour, possibly reflecting common effects of pituitary hormones on puberty and pigmentation. Earlier male puberty timing is genetically correlated with several adverse health outcomes and, in Mendelian randomization analyses, shows causal relationships with higher risk of prostate cancer and shorter lifespan. These findings highlight the relationships between puberty timing and later health outcomes, and demonstrate the value of genetic studies of puberty timing in both sexes.

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“…10,11 Women have a higher prevalence of lighter hair colour and fairer skin than men. 12,13 The interaction between sex and genetic variants associated with tanning facility has been reported recently. 14 MC1R is a highly polymorphic gene in the white population and one of the most important regulator genes in human skin and hair pigmentation.…”

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confidence: 97%

Inherited MC 1R variants in patients with melanoma are associated with better survival in women

et al. 2019

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Summary Background Women have a better melanoma prognosis, and fairer skin/hair colour. The presence of inherited MC1R variants has been associated with a better melanoma prognosis, but its interaction with sex is unknown. Objectives To evaluate the relationship between germline MC1R status and survival, and determine any association with sex. Methods This was a cohort study including 1341 patients with melanoma from the Melanoma Unit of the Hospital Clinic of Barcelona, between January 1996 and April 2018. We examined known sex‐related prognosis factors as they relate to features of melanoma and evaluated the sex‐specific role of MC1R in overall and melanoma‐specific survival. Hazard ratios (HRs) were calculated using univariate and multivariate Cox logistic regression. Results Men showed lower overall survival than women (P < 0·001) and the presence of inherited MC1R variants was not associated with better survival in our cohort. However, in women the presence of MC1R variants was associated with better overall survival in the multivariate analysis [HR 0·57, 95% confidence interval (CI) 0·38–0·85; P = 0·006] but not in men [HR 1·26, 95% CI 0·89–1·79; P = 0·185 (P‐value for interaction 0·004)]. Analysis performed for melanoma‐specific survival showed the same level of significance. Conclusions Inherited MC1R variants are associated with improved overall survival in women with melanoma but not in men. Intrinsic sex‐dependent features can modify the role of specific genes in melanoma prognosis. We believe that survival studies of patients with melanoma should include analysis by sex and MC1R genotype. What's already known about this topic? Inherited MC1R variants have been associated with a better melanoma prognosis, but their interaction with sex is unknown. What does this study add? MC1R variants are related to better overall survival and melanoma‐specific survival in women but not in men. What is the translational message? These differences between the sexes could imply future changes in melanoma follow‐up and treatment strategies. This provides a basis for understanding the interaction between sex‐related genes and germline variants in cancer.

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Genome-wide association meta-analysis of individuals of European ancestry identifies new loci explaining a substantial fraction of hair color variation and heritability

Cited by 91 publications

References 48 publications

The biology of human hair: A multidisciplinary review

The biology of human hair: A multidisciplinary review

Expanded genomic analyses for male voice-breaking highlights a shared phenotypic and genetic basis between puberty timing and hair colour

Inherited MC 1R variants in patients with melanoma are associated with better survival in women

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