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Polygenic risk score for alcohol drinking behavior improves prediction of inflammatory bowel disease risk.
Di Narzo, Antonio F; Hart, Amy; Kosoy, Roman; Peters, Lauren; Stojmirovic, Aleksandar; Cheng, Haoxiang; Zhang, Zhongyang; Shan, Mingxu; Cho, Judy; Kasarskis, Andrew; Argmann, Carmen; Peter, Inga; Schadt, Eric E; Hao, Ke.
Afiliación
  • Di Narzo AF; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Hart A; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Kosoy R; Immunology Translational Sciences, Janssen R&D, LLC, Spring House, PA 19477, USA.
  • Peters L; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Stojmirovic A; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Cheng H; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Zhang Z; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Shan M; Statistical Genomics, Sema4, Stamford, CT 06902, USA.
  • Cho J; Immunology Translational Sciences, Janssen R&D, LLC, Spring House, PA 19477, USA.
  • Kasarskis A; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Argmann C; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Peter I; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Schadt EE; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Hao K; Statistical Genomics, Sema4, Stamford, CT 06902, USA.
Hum Mol Genet ; 30(6): 514-523, 2021 04 30.
Article en En | MEDLINE | ID: mdl-33601420
Epidemiological studies have long recognized risky behaviors as potentially modifiable factors for the onset and flares of inflammatory bowel disease (IBD); yet, the underlying mechanisms are largely unknown. Recently, the genetic susceptibilities to cigarette smoking, alcohol and cannabis use [i.e. substance use (SU)] have been characterized by well-powered genome-wide association studies (GWASs). We aimed to assess the impact of genetic determinants of SU on IBD risk. Using Mount Sinai Crohn's and Colitis Registry (MSCCR) cohort of 1058 IBD cases and 188 healthy controls, we computed the polygenic risk score (PRS) for SU and correlated them with the observed IBD diagnoses, while adjusting for genetic ancestry, PRS for IBD and SU behavior at enrollment. The results were validated in a pediatric cohort with no SU exposure. PRS of alcohol consumption (DrnkWk), smoking cessation and age of smoking initiation, were associated with IBD risk in MSCCR even after adjustment for PRSIBD and actual smoking status. One interquartile range decrease in PRSDrnkWk was significantly associated to higher IBD risk (i.e. inverse association) (with odds ratio = 1.65 and 95% confidence interval: 1.32, 2.06). The association was replicated in a pediatric Crohn's disease cohort. Colocalization analysis identified a locus on chromosome 16 with polymorphisms in IL27, SULT1A2 and SH2B1, which reached genome-wide statistical significance in GWAS (P < 7.7e-9) for both alcohol consumption and IBD risk. This study demonstrated that the genetic predisposition to SU was associated with IBD risk, independent of PRSIBD and in the absence of SU behaviors. Our study may help further stratify individuals at risk of IBD.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Consumo de Bebidas Alcohólicas / Biomarcadores / Enfermedades Inflamatorias del Intestino / Predisposición Genética a la Enfermedad / Polimorfismo de Nucleótido Simple / Estudio de Asociación del Genoma Completo Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Aspecto: Patient_preference Límite: Adolescent / Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Revista: Hum Mol Genet Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Consumo de Bebidas Alcohólicas / Biomarcadores / Enfermedades Inflamatorias del Intestino / Predisposición Genética a la Enfermedad / Polimorfismo de Nucleótido Simple / Estudio de Asociación del Genoma Completo Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Aspecto: Patient_preference Límite: Adolescent / Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Revista: Hum Mol Genet Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido