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Genome-Wide Association Study Identifies Genetic Loci Associated With Fat Cell Number and Overlap With Genetic Risk Loci for Type 2 Diabetes.
Kulyté, Agné; Aman, Alisha; Strawbridge, Rona J; Arner, Peter; Dahlman, Ingrid A.
Afiliación
  • Kulyté A; Lipid Laboratory, Endocrinology Unit, Department of Medicine Huddinge, Karolinska Institutet, Huddinge, Sweden.
  • Aman A; Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, U.K.
  • Strawbridge RJ; Institute of Health and Wellbeing, University of Glasgow, Glasgow, U.K.
  • Arner P; Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
  • Dahlman IA; Lipid Laboratory, Endocrinology Unit, Department of Medicine Huddinge, Karolinska Institutet, Huddinge, Sweden.
Diabetes ; 71(6): 1350-1362, 2022 06 01.
Article en En | MEDLINE | ID: mdl-35320353
Interindividual differences in generation of new fat cells determine body fat and type 2 diabetes risk. In the GENetics of Adipocyte Lipolysis (GENiAL) cohort, which consists of participants who have undergone abdominal adipose biopsy, we performed a genome-wide association study (GWAS) of fat cell number (n = 896). Candidate genes from the genetic study were knocked down by siRNA in human adipose-derived stem cells. We report 318 single nucleotide polymorphisms (SNPs) and 17 genetic loci displaying suggestive (P < 1 × 10-5) association with fat cell number. Two loci pass threshold for GWAS significance, on chromosomes 2 (lead SNP rs149660479-G) and 7 (rs147389390-deletion). We filtered for fat cell number-associated SNPs (P < 1.00 × 10-5) using evidence of genotype-specific expression. Where this was observed we selected genes for follow-up investigation and hereby identified SPATS2L and KCTD18 as regulators of cell proliferation consistent with the genetic data. Furthermore, 30 reported type 2 diabetes-associated SNPs displayed nominal and consistent associations with fat cell number. In functional follow-up of candidate genes, RPL8, HSD17B12, and PEPD were identified as displaying effects on cell proliferation consistent with genetic association and gene expression findings. In conclusion, findings presented herein identify SPATS2L, KCTD18, RPL8, HSD17B12, and PEPD of potential importance in controlling fat cell numbers (plasticity), the size of body fat, and diabetes risk.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diabetes Mellitus Tipo 2 / Estudio de Asociación del Genoma Completo Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Diabetes Año: 2022 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diabetes Mellitus Tipo 2 / Estudio de Asociación del Genoma Completo Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Diabetes Año: 2022 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Estados Unidos