MOLECULAR PATHWAYS ANALYSIS THROUGH MULTI-OMICS APPROACHES TO STUDY THE BIOLOGICAL BASIS OF ANOREXIA NERVOSA
type: CreativeWork
description: Anorexia nervosa is a complex and multifactorial disorder with a high genetic component and severe metabolic consequences. Despite its high heritability, the molecular mechanisms underlying AN remain unclear, and current treatment strategies are often ineffective. Recent advancements in genomics and metabolomics offer promising tools for understanding the genetic and biochemical pathways involved in AN. This study aimed to investigate the genetic and metabolomic basis of AN using next-generation sequencing, polygenic risk scoring, and hair metabolomic profiling, with the ultimate goal of improving diagnosis and treatment strategies. This study analyzed three distinct case studies involving AN patients. The first case study involved sequencing the DNA of 68 AN patients using a panel of 162 genes to identify rare variants associated with the disorder. The second case study expanded the cohort to 135 AN patients and included the calculation of PRS using a newly designed panel of 163 genes and 730 single nucleotide polymorphisms. The third case study focused on metabolomic analysis of hair samples from 25 AN patients and 25 healthy controls, with an emphasis on amino acid and carnitine profiles. NGS, statistical analysis, and machine learning algorithms were employed to analyze genetic variants and metabolomic profiles. In the first case study, rare variants in key genes were identified, suggesting a potential monogenic form of AN. The second case study revealed a significant genetic contribution to AN risk, with the PRS explaining 21.3% of the variance in the phenotype. Variants in genes related to dopamine signaling, skeletal muscle function, and appetite regulation were identified, highlighting diverse molecular mechanisms contributing to AN. The third case study demonstrated significant metabolic alterations in AN patients, particularly deficiencies in branched-chain amino acids and essential amino acids. These findings suggest a biochemical basis for appetite dysre…
abstract: Anorexia nervosa is a complex and multifactorial disorder with a high genetic component and severe metabolic consequences. Despite its high heritability, the molecular mechanisms underlying AN remain unclear, and current treatment strategies are often ineffective. Recent advancements in genomics and metabolomics offer promising tools for understanding the genetic and biochemical pathways involved in AN. This study aimed to investigate the genetic and metabolomic basis of AN using next-generation sequencing, polygenic risk scoring, and hair metabolomic profiling, with the ultimate goal of improving diagnosis and treatment strategies. This study analyzed three distinct case studies involving AN patients. The first case study involved sequencing the DNA of 68 AN patients using a panel of 162 genes to identify rare variants associated with the disorder. The second case study expanded the cohort to 135 AN patients and included the calculation of PRS using a newly designed panel of 163 genes and 730 single nucleotide polymorphisms. The third case study focused on metabolomic analysis of hair samples from 25 AN patients and 25 healthy controls, with an emphasis on amino acid and carnitine profiles. NGS, statistical analysis, and machine learning algorithms were employed to analyze genetic variants and metabolomic profiles. In the first case study, rare variants in key genes were identified, suggesting a potential monogenic form of AN. The second case study revealed a significant genetic contribution to AN risk, with the PRS explaining 21.3% of the variance in the phenotype. Variants in genes related to dopamine signaling, skeletal muscle function, and appetite regulation were identified, highlighting diverse molecular mechanisms contributing to AN. The third case study demonstrated significant metabolic alterations in AN patients, particularly deficiencies in branched-chain amino acids and essential amino acids. These findings suggest a biochemical basis for appetite dysre…
author: DONATO, KEVIN
language: eng
keywords: Anorexia nervosa: Genomic, Metabolomic, Next-generation sequencing, Polygenic Risk Score, Diagnostic genetics, Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica, Settore BIOS-09/A - Biochimica clinica e biologia molecolare clinica
date published: 2025-01-24
date modified: 2026-07-27T20:18:48Z
provider: Università degli Studi di Milano
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Università degli Studi di Milano

PropertyValue
property ID: Handle
value: https://hdl.handle.net/2434/1114051

PropertyValue
property ID: DOI
value: 10.13130/donato-kevin_phd2025-01-24