Pleiotropy within gene variants associated with nonalcoholic fatty liver disease and traits of the hematopoietic system

©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved..

Genome-wide association studies of complex diseases, including nonalcoholic fatty liver disease (NAFLD), have demonstrated that a large number of variants are implicated in the susceptibility of multiple traits - a phenomenon known as pleiotropy that is increasingly being explored through phenome-wide association studies. We focused on the analysis of pleiotropy within variants associated with hematologic traits and NAFLD. We used information retrieved from large public National Health and Nutrition Examination Surveys, Genome-wide association studies, and phenome-wide association studies based on the general population and explored whether variants associated with NAFLD also present associations with blood cell-related traits. Next, we applied systems biology approaches to assess the potential biological connection/s between genes that predispose affected individuals to NAFLD and nonalcoholic steatohepatitis, and genes that modulate hematological-related traits-specifically platelet count. We reasoned that this analysis would allow the identification of potential molecular mediators that link NAFLD with platelets. Genes associated with platelet count are most highly expressed in the liver, followed by the pancreas, heart, and muscle. Conversely, genes associated with NAFLD presented high expression levels in the brain, lung, spleen, and colon. Functional mapping, gene prioritization, and functional analysis of the most significant loci (P < 1 × 10-8) revealed that loci involved in the genetic modulation of platelet count presented significant enrichment in metabolic and energy balance pathways. In conclusion, variants in genes influencing NAFLD exhibit pleiotropic associations with hematologic traits, particularly platelet count. Likewise, significant enrichment of related genes with variants influencing platelet traits was noted in metabolic-related pathways. Hence, this approach yields novel mechanistic insights into NAFLD pathogenesis.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:27

Enthalten in:

World journal of gastroenterology - 27(2021), 4 vom: 28. Jan., Seite 305-320

Sprache:

Englisch

Beteiligte Personen:

Pirola, Carlos Jose [VerfasserIn]
Salatino, Adrian [VerfasserIn]
Sookoian, Silvia [VerfasserIn]

Links:

Volltext

Themen:

Genetics
Hematologic traits
Journal Article
Leukocytes
Nonalcoholic fatty liver disease
Nonalcoholic steatohepatitis
Platelets
Review

Anmerkungen:

Date Completed 14.05.2021

Date Revised 14.05.2021

published: Print

Citation Status MEDLINE

doi:

10.3748/wjg.v27.i4.305

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM321436938