A genome-wide association study of maternal genetic effects in autism spectrum disorder

master's thesis

• Title (croatian): Analiza utjecaja majčinog genotipa na razvoj poremećaja iz spektra autizma kod djece metodom genomske asocijacije
• Author: Kim Vučinić
• Mentor: Denis Shields (mentor)
• Mentor: Kristian Vlahoviček (sumentor)
• Committee member: Kristian Vlahoviček (predsjednik povjerenstva)
• Committee member: Sofia Ana Blažević (član povjerenstva)
• Committee member: Damjan Franjević (član povjerenstva)
• Committee member: Rosa Karlić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2021-02-26, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Around 2% of children in the world are diagnosed with autism spectrum disorder
(ASD), a family of conditions influenced by both genetic and environmental factors.
Findings suggest that maternal genetic composition affects the development of
ASD in offspring. The subject matter is underresearched and the replication of
findings is problematic. The aim of this study was to identify potential candidate
loci in mothers that might increase the risk of development of ASD in offspring. A
case-control genome-wide association study was performed on the SPARK dataset
(n = 27,290) that consists of quad, trio and duo families where one or multiple
individuals can be affected. Affected children’s mothers were used as cases and
affected children’s fathers as controls. Maternal genetic effects were also modelled
with log-linear models proposed by Weinberg (1999). In addition, permutation tests
were used to assess the significance of the Bayes factor that was used to rank SNPs
according to their degree of association. The results indicate involvement of maternal
genetic effect in the offspring’s development. The finding of variants associated with
increased risk of developing ASD is important for understanding the aetiology of
ASD, which could lead to better personalized medicine in the future.

Abstract (croatian)

Otprilike 2% djece u svijetu je dijagnosticirano s poreme´cajem iz spektra autizma,
neurorazvojnim poreme´cajem koji ima genetske i okolišne uzroke. Istraživanja
ukazuju na mogu´cnost utjecaja majˇcinog genotipa na razvoj autizma kod djeteta.
Problematika je nedovoljno istražena te je replikacija potencijalnih kandidata u ve´cini
sluˇcajeva neuspjela. Cilj ovog diplomskog rada je bio identificirati potencijalne
genske markere u majkama koji pove´cavaju rizik razvoja poreme´caja iz spektra
autizma kod djece. U ovom radu, genomska analiza je provedena na skupu podataka
SPARK (n = 27 290) koji se sastoji od ˇcetveroˇclanih, troˇclanih i dvoˇclanih obitelji
gdje je jedan ili više pojedinaca dijagnosticirano s poreme´cajem iz spektra autizma.
Eksperiment je dizajniran tako da su majke sluˇcajevi, a oˇcevi kontrole u genomskoj
analizi. Utjecaj majˇcinog genotipa je modeliran Weinberg log-linearnim modelom.
Permutacijom je odred¯ena znacˇajnost geneticˇkih markera koji su rangirani ovisno
o jaˇcini asocijacije po Bayesovom faktoru. Rezultati ukazuju na utjecaj majˇcinog
genotipa na razvoj poreme´caja kod djece. Istraživanje genetiˇckih markera asociranih
s pove´canim rizikom za razvoj poreme´caja iz spektra autizma je bitno za bolje
razumijevanje etiologije autizma, što može poboljšati personaliziranu medicinu u
budu´cnosti.

• Keywords: GWAS; case-control study; ASD; maternal genetic effects; Bayesian statistics; permutations
• Keywords (croatian): GWAS; case-control study; ASD; utjecaj majˇcinog genotipa; Bayes statistika; permutacije
• Language: english
• URN:NBN: urn:nbn:hr:217:168612
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-07-22 10:16:50