Identification of genes promoting skin youthfulness by genome-wide association study

Anne L S Chang, Gil Atzmon, Aviv Bergman, Samantha Brugmann, Scott X. Atwood, Howard Y. Chang, Nir Barzilai

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

To identify genes that promote facial skin youthfulness (SY), a genome-wide association study on an Ashkenazi Jewish discovery group (n=428) was performed using Affymetrix 6.0 Single-Nucleotide Polymorphism (SNP) Array. After SNP quality controls, 901,470 SNPs remained for analysis. The eigenstrat method showed no stratification. Cases and controls were identified by global facial skin aging severity including intrinsic and extrinsic parameters. Linear regression adjusted for age and gender, with no significant differences in smoking history, body mass index, menopausal status, or personal or family history of centenarians. Six SNPs met the Bonferroni threshold with P allele <10 -8; two of these six had P genotype <10 -8. Quantitative trait loci mapping confirmed linkage disequilibrium. The six SNPs were interrogated by MassARRAY in a replication group (n=436) with confirmation of rs6975107, an intronic region of KCND2 (potassium voltage-gated channel, Shal-related family member 2) (P genotype =0.023). A second replication group (n=371) confirmed rs318125, downstream of DIAPH2 (diaphanous homolog 2 (Drosophila)) (P allele =0.010, P genotype =0.002) and rs7616661, downstream of EDEM1 (ER degradation enhancer, mannosidase α-like 1) (P genotype =0.042). DIAPH2 has been associated with premature ovarian insufficiency, an aging phenotype in humans. EDEM1 associates with lifespan in animal models, although not humans. KCND2 is expressed in human skin, but has not been associated with aging. These genes represent new candidate genes to study the molecular basis of healthy skin aging.

Original languageEnglish (US)
Pages (from-to)651-657
Number of pages7
JournalJournal of Investigative Dermatology
Volume134
Issue number3
DOIs
StatePublished - Mar 2014

Fingerprint

Genome-Wide Association Study
Single Nucleotide Polymorphism
Skin
Genes
Aging of materials
Mannosidases
Association reactions
Genotype
Skin Aging
Polymorphism
Nucleotides
Voltage-Gated Potassium Channels
Degradation
Alleles
Linear regression
Quantitative Trait Loci
Quality control
Linkage Disequilibrium
Animals
Quality Control

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Identification of genes promoting skin youthfulness by genome-wide association study. / Chang, Anne L S; Atzmon, Gil; Bergman, Aviv; Brugmann, Samantha; Atwood, Scott X.; Chang, Howard Y.; Barzilai, Nir.

In: Journal of Investigative Dermatology, Vol. 134, No. 3, 03.2014, p. 651-657.

Research output: Contribution to journalArticle

Chang, Anne L S ; Atzmon, Gil ; Bergman, Aviv ; Brugmann, Samantha ; Atwood, Scott X. ; Chang, Howard Y. ; Barzilai, Nir. / Identification of genes promoting skin youthfulness by genome-wide association study. In: Journal of Investigative Dermatology. 2014 ; Vol. 134, No. 3. pp. 651-657.
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