rs1805007

This study identified rs41305272, a predicted miR-330-3p target site SNP in MAP2K5, as associated with anxiety and depressive disorders in 6,725 European-American and African-American subjects. The T-allele was significantly associated with agoraphobia (OR=2.22, p=0.0004 combined sample), panic disorder (OR=1.95, p=0.002), and major depressive disorder (OR=1.48, p=0.01). The rs41305272 SNP is in linkage disequilibrium with a restless legs syndrome GWAS variant and showed pathway enrichment for nervous system development genes.

Genome-wide association study of sagging eyelids (dermatochalasis) in 5,578 Rotterdam Study participants and 1,053 TwinsUK twins identified a genome-wide significant protective effect for the C allele of rs11876749 (P=1.7×10⁻⁸) in a recessive model. Risk factors included age, male sex, lighter skin color, and higher BMI. Heritability of sagging eyelids was estimated at 61% in the twin cohort.

This study examined associations between sun-sensitive pigmentary gene variants and serum PSA levels in 1033 older Australian men. Variants in SLC45A2 (rs28777: -19.6%, rs16891982: -17.3%) were associated with lower PSA levels in all men. Variants in MC1R (rs1805007) and ASIP (rs4911414) showed significant interactions with birth region, with higher PSA levels in ANZ-born men carrying the variants. Post-hoc analysis found increased testosterone in MC1R rs1805007 carriers and elevated dihydrotestosterone in ASIP rs1015362 carriers.

This genome-wide association study (GWAS) of pigmentary traits in East Asian populations (N=305 skin, N=342 iris) identifies a genome-wide significant signal for iris color in the OCA2 region, with rs1800414 (His615Arg) explaining 11.9%, 10.4%, and 6% of variation in b*, a*, and L* coordinates respectively. While no genome-wide significant signals were detected for skin pigmentation, rs2373391 in ZNF804B was replicated in independent Chinese samples (p=0.003).

Genetic association study of 202 melanoma patients examining SNPs in 24 candidate genes related to pigmentation and wound healing in relation to scar outcome. SNP rs8110090 in TGFβ1 was significantly associated with poorer scar outcomes (p=0.0002). Clinical factors including younger age, shorter time since surgery, and presence of infection or eczema were also associated with worse scarring.

This candidate gene association study examined five CHRNA4 SNPs in 1,249 European-Americans and 1,790 African-Americans to evaluate associations with smoking behavior. The synonymous SNP rs1044394 was significantly associated with nicotine dependence (DSM-IV ND: P=0.001; FTND: P=0.01) and remained significant after multiple testing correction for ND (P=0.033). Rs2236196 was associated with cigarettes per day (P=0.003), with similar association patterns observed in both ancestry groups.

This study demonstrates that human hair color can be predicted from DNA variants with high accuracy using a multinomial logistic regression model. A subset of 13 genetic markers from 11 genes (MC1R, HERC2, IRF4, TYR, EXOC2, SLC45A2, TYRP1, OCA2, SLC24A4, KITLG, ASIP) predicted hair color categories in Polish Europeans with AUC values of 0.93 for red hair, 0.87 for black hair, 0.82 for brown hair, and 0.81 for blond hair. MC1R variants showed the strongest association with red hair (OR=12.64 for R variants, P=2.5×10⁻¹⁷), while rs12913832 in HERC2 was significantly associated with darker hair colors (OR=3.33 for black, P=4.3×10⁻⁶).

This paper reports the discovery of Arg151Cys (c.451C>T), a nonfunctional point mutation in the MC1R (melanocortin 1 receptor) gene found in a person with red hair and light skin type I. The mutant receptor binds α-MSH with identical affinity to wild-type (Kd 0.084 nM) but cannot be stimulated to produce cAMP, explaining the red hair, light skin, and poor tanning ability.