TABLE 2—
Major Genome-Wide Association Studies (GWASs) Incorporating Nurses’ Health Study (NHS) Data
| Authors | Phenotype | Major Findings |
| Han et al.39 | Hair color, skin color, tanning ability, eye color | This GWAS linked the IRF4 (6p25-p23) and SLC24A4 (14q32) loci to human pigmentation for the first time; the study also identified 3 chromosome regions adjacent to the previously known pigmentation genes: MC1R (16q24), OCA2/HERC2 (15q11-q13), and MATP (5p13) |
| Nan et al. (2009) | Tanning ability | This GWAS confirmed the prior known pigmentation genes (MATP, IRF4, TYR, OCA2, MC1R) associated with tanning ability |
| Nan et al. (2011) | Number of melanocytic nevi (moles); melanoma only in the post-GWAS candidate gene analysis | This GWAS identified rs3768080 and rs10754833 (NID1, 1q42), associated with nevus count; also, rs10754833 was associated with melanoma risk |
| Nan et al.40 | BCC; SCC and melanoma only in the post-GWAS candidate gene analysis | rs1805007 in MC1R showed the strongest association with BCC risk in the discovery set; this study showed that rs12210050 (near EXOC2, 6p25) and rs7335046 (near UBAC2, 13q32) confer susceptibility to BCC; further candidate gene analysis revealed associations of these 2 SNPs with risk of SCC but not melanoma |
| Amos et al. (2011)a | Melanoma | This GWAS identified novel SNPs in HERC2/OCA2 (15q13.1) as well as an intergenic region of chromosome 1q21.3 associated with melanoma risk; it also confirmed associations for several previously identified regions: MATP, CDKN2A, TYR, MC1R, a broad region in 20q11, and a region of 22q13 encompassing PLA2G6 |
| Zhang et al.41 | Hair color, eye color, number of sunburns, tanning ability, number of keratinocyte carcinomas | A new region downstream of EDNRB (13q22) was associated with hair color; Rs3002288 in VASH2 (1q32.3) was associated with brown eye color; 2 SNPs in the ITRF4-EXOC2 region (6p25-p23) and 1 SNP upstream of GNG2 (14q22) were associated with number of keratinocyte carcinomas |
| Song et al. (2014) | Melanoma | This GWAS identified a novel SNP, rs4698934 (TET2, 4q24), associated with melanoma; next-generation sequencing further identified a novel somatic mutation in melanoma |
| Zhang et al. (2014)b | Severe adolescent acne | rs4133274 (upstream of MYC, 8q24) revealed the most significant association |
| Siiskonen et al. (2016) | SCC | This GWAS identified rs8063761 (DEF8, 16q24) and several other genetic variants associated with risk of SCC |
Note. BCC = basal cell carcinoma; SCC = squamous cell carcinoma; SNP = single nucleotide polymorphism. The studies included are major studies with NHS investigators as the leading (or co-leading) or senior (or co-senior) authors.
a
NHS data contributed only to the replication stage of this study.
b
This study did not include the GWAS discovery replication phase.