title: Identification of genes promoting skin youthfulness by genome-wide association study.
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 Pallele<10(-8); two of these six had Pgenotype<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) (Pgenotype=0.023). A second replication group (n=371) confirmed rs318125, downstream of DIAPH2 (diaphanous homolog 2 (Drosophila)) (Pallele=0.010, Pgenotype=0.002) and rs7616661, downstream of EDEM1 (ER degradation enhancer, mannosidase α-like 1) (Pgenotype=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.
authors.affiliation: Department of Dermatology, Stanford University School of Medicine, Redwood City, California, USA. Electronic address: alschang@stanford.edu.
authors.forename: Anne L S
authors.initials: ALS
authors.lastname: Chang
authors.affiliation: Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Gil
authors.initials: G
authors.lastname: Atzmon
authors.affiliation: Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Aviv
authors.initials: A
authors.lastname: Bergman
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital and Medical Center, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Brugmann
authors.affiliation: Department of Dermatology, Stanford University School of Medicine, Redwood City, California, USA.
authors.forename: Scott X
authors.initials: SX
authors.lastname: Atwood
authors.affiliation: Department of Dermatology, Stanford University School of Medicine, Redwood City, California, USA.
authors.forename: Howard Y
authors.initials: HY
authors.lastname: Chang
authors.affiliation: Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Nir
authors.initials: N
authors.lastname: Barzilai
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D005145:Face; D005260:Female; D000080865:Formins; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007585:Jews / Q000235:genetics*; D007801:Langerhans Cells / Q000502:physiology; D016014:Linear Models; D015810:Linkage Disequilibrium; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D051672:Shal Potassium Channels / Q000235:genetics*; D015595:Skin Aging / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; C491462:DIAPH2 protein, human; C486654:EDEM1 protein, human; D000080865:Formins; C497018:KCND2 protein, human; D008565:Membrane Proteins; D051672:Shal Potassium Channels
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