Leveraging genome-wide association statistics generated from a large study of amyotrophic lateral sclerosis (ALS; 29,612 cases and 122,656 controls) and UK Biobank (UKB; 4,024 phenotypes, up to 361,194 participants), we conducted a phenome-wide analysis of ALS genetic liability and identified 46 genetically correlated traits, such as fluid intelligence score (rg = − 0.21, p = 1.74 × 10–6), "spending time in pub or social club” (rg = 0.24, p = 2.77 × 10–6), non-work related walking (rg = − 0.25, p = 1.95 × 10–6), college education (rg = − 0.15, p = 7.08 × 10–5), “ever diagnosed with panic attacks (rg = 0.39, p = 4.24 × 10–5), and “self-reported other gastritis including duodenitis” (rg = 0.28, p = 1.4 × 10–3). To assess the putative directionality of these genetic correlations, we conducted a latent causal variable analysis, identifying significant genetic causality proportions (gĉp) linking ALS genetic liability to seven traits. While the genetic component of “self-reported other gastritis including duodenitis" showed a causal effect on ALS (gĉp = 0.50, p = 1.26 × 10–29), the genetic liability to ALS is potentially causal for multiple traits, also including an effect on "ever being diagnosed with panic attacks” (gĉp = 0.79, p = 5.011 × 10–15) and inverse effects on “other leisure/social group activities” (gĉp = 0.66, p = 1 × 10–4) and prospective memory result (gĉp = 0.35, p = 0.005). Our subsequent Mendelian randomization analysis indicated that some of these associations may be due to bidirectional effects. In conclusion, this phenome-wide investigation of ALS polygenic architecture highlights the widespread pleiotropy linking this disorder with several health domains.

D'Antona, S., Pathak, G., Koller, D., Porro, D., Cava, C., Polimanti, R. (2023). Phenome-wide genetic-correlation analysis and genetically informed causal inference of amyotrophic lateral sclerosis. HUMAN GENETICS, 142(8), 1173-1183 [10.1007/s00439-023-02525-5].

Phenome-wide genetic-correlation analysis and genetically informed causal inference of amyotrophic lateral sclerosis

D'Antona, S;Porro, D;
2023

Abstract

Leveraging genome-wide association statistics generated from a large study of amyotrophic lateral sclerosis (ALS; 29,612 cases and 122,656 controls) and UK Biobank (UKB; 4,024 phenotypes, up to 361,194 participants), we conducted a phenome-wide analysis of ALS genetic liability and identified 46 genetically correlated traits, such as fluid intelligence score (rg = − 0.21, p = 1.74 × 10–6), "spending time in pub or social club” (rg = 0.24, p = 2.77 × 10–6), non-work related walking (rg = − 0.25, p = 1.95 × 10–6), college education (rg = − 0.15, p = 7.08 × 10–5), “ever diagnosed with panic attacks (rg = 0.39, p = 4.24 × 10–5), and “self-reported other gastritis including duodenitis” (rg = 0.28, p = 1.4 × 10–3). To assess the putative directionality of these genetic correlations, we conducted a latent causal variable analysis, identifying significant genetic causality proportions (gĉp) linking ALS genetic liability to seven traits. While the genetic component of “self-reported other gastritis including duodenitis" showed a causal effect on ALS (gĉp = 0.50, p = 1.26 × 10–29), the genetic liability to ALS is potentially causal for multiple traits, also including an effect on "ever being diagnosed with panic attacks” (gĉp = 0.79, p = 5.011 × 10–15) and inverse effects on “other leisure/social group activities” (gĉp = 0.66, p = 1 × 10–4) and prospective memory result (gĉp = 0.35, p = 0.005). Our subsequent Mendelian randomization analysis indicated that some of these associations may be due to bidirectional effects. In conclusion, this phenome-wide investigation of ALS polygenic architecture highlights the widespread pleiotropy linking this disorder with several health domains.
Articolo in rivista - Articolo scientifico
amyotrophic lateral sclerosis
English
11-feb-2023
2023
142
8
1173
1183
open
D'Antona, S., Pathak, G., Koller, D., Porro, D., Cava, C., Polimanti, R. (2023). Phenome-wide genetic-correlation analysis and genetically informed causal inference of amyotrophic lateral sclerosis. HUMAN GENETICS, 142(8), 1173-1183 [10.1007/s00439-023-02525-5].
File in questo prodotto:
File Dimensione Formato  
10281-434218_VoR.pdf

accesso aperto

Tipologia di allegato: Publisher’s Version (Version of Record, VoR)
Licenza: Creative Commons
Dimensione 1.31 MB
Formato Adobe PDF
1.31 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/434218
Citazioni
  • Scopus 2
  • ???jsp.display-item.citation.isi??? 2
Social impact