Laura Addis
A5021217067- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Language Development and Disorders
- Genomic variations and chromosomal abnormalities
- Genetic Associations and Epidemiology
- Epilepsy research and treatment
- RNA and protein synthesis mechanisms
- Sleep and related disorders
- Reading and Literacy Development
- Immune Cell Function and Interaction
- Sleep and Wakefulness Research
- BRCA gene mutations in cancer
- Chronic Disease Management Strategies
- Machine Learning in Bioinformatics
- Machine Learning in Healthcare
- Pregnancy and preeclampsia studies
- Cell Adhesion Molecules Research
- Neuroscience and Neuropharmacology Research
- Bioinformatics and Genomic Networks
- Osteoarthritis Treatment and Mechanisms
- RNA Research and Splicing
- Gynecological conditions and treatments
- Cannabis and Cannabinoid Research
- Epigenetics and DNA Methylation
- Endometriosis Research and Treatment
Institute for Molecular Medicine Finland
2025
University of Helsinki
2025
Age UK
2024
GlaxoSmithKline (United Kingdom)
2021-2024
King's College London
2010-2020
Eli Lilly (United Kingdom)
2015-2020
Eli Lilly (United States)
2016-2020
Neuroscience Institute
2018
Wellcome Centre for Human Neuroimaging
2016
University College London
2016
Abstract The availability of high-quality RNA-sequencing and genotyping data post-mortem brain collections from consortia such as CommonMind Consortium (CMC) the Accelerating Medicines Partnership for Alzheimer’s Disease (AMP-AD) enable generation a large-scale cis- eQTL meta-analysis. Here we generate cerebral cortical 1433 samples available four cohorts (identifying >4.1 million significant >18,000 genes), well cerebellar 261 874,836 >10,000 genes). We find substantially improved...
Dyslexia (or reading disability) and specific language impairment SLI) are common childhood disorders that show considerable co-morbidity diagnostic overlaps have been suggested to share some genetic aetiology. Recently, risk variants identified for SLI dyslexia enabling the direct evaluation of possible shared influences between these disorders. In this study we investigate role in genes (namely MRPL19/C20RF3, ROBO1, DCDC2, KIAA0319, DYX1C1, CNTNAP2, ATP2C2 CMIP) aetiology dyslexia. We...
Abstract Mutations in the N-methyl-D-aspartate receptor (NMDAR) gene GRIN2A cause epilepsy-aphasia syndrome (EAS), a spectrum of epileptic, cognitive and language disorders. Using bioinformatic patient data we shortlisted 10 diverse missense mutations for characterisation. We used high-throughput calcium-flux assays patch clamp recordings transiently transfected HEK-293 cells electrophysiological characterization, Western blotting confocal imaging to assay expression surface trafficking....
Abstract Large-scale biobank initiatives and commercial repositories store genomic data collected from millions of individuals, tools to leverage the rapidly growing pool health in disease prevention are needed. Here, we describe derivation validation genomics-enhanced risk for two common cardiometabolic diseases, coronary heart type 2 diabetes. Data used our analyses include FinnGen study (N = 309,154) UK Biobank project 343,672). The integrate contemporary genome-wide polygenic scores with...
Deficits in phonological short‐term memory and aspects of verb grammar morphology have been proposed as phenotypic markers specific language impairment (SLI) with the suggestion that these traits are likely to be under different genetic influences. This investigation 300 first‐degree relatives 93 probands SLI examined familial aggregation linkage two measures thought index traits, non‐word repetition tense marking. In particular, involvement chromosomes 16q 19q was previous studies found...
Abstract Objective We aimed to describe the extent of neurodevelopmental impairments and identify genetic etiologies in a large cohort patients with epilepsy myoclonic atonic seizures (MAE). Methods deeply phenotyped MAE for features, intellectual disability, autism spectrum disorder, attention‐deficit/hyperactivity disorder using standardized neuropsychological instruments. performed exome analysis (whole sequencing) filtered on neuropsychiatric gene sets etiologies. Results analyzed 101...
Uterine leiomyomata (UL) are the most common tumours of female genital tract and primary cause surgical removal uterus. Genetic factors contribute to UL susceptibility. To add understanding heritable genetic risk factors, we conduct a genome-wide association study (GWAS) in up 426,558 European women from FinnGen previous meta-GWAS. In addition 50 known loci, identify 22 loci that have not been associated with prior studies. UL-associated harbour genes enriched for development, growth,...
Narcolepsy is a severe sleep disorder with characteristics of fatigue, fragmented sleep, cataplexy and hypnagogic hallucinations. Earlier clinical studies have reported the onset schizophrenia after narcolepsy but causality behind unknown. Our goal was to understand between schizophrenia. To estimate comorbidity schizophrenia, we employed data from FinRegistry that contains for total population Finland in 7.2 million individuals (N = 1664 55,372 schizophrenia). We then used Mendelian...
Aim Sex chromosome aneuploidies increase the risk of spoken or written language disorders but individuals with specific impairment ( SLI ) dyslexia do not routinely undergo cytogenetic analysis. We assess frequency sex in dyslexia. Method Genome‐wide single nucleotide polymorphism genotyping was performed three sample sets: a clinical cohort speech and deficits (87 probands: 61 males, 26 females; age range 4 to 23 years), replication , from both epidemiological samples (209 139 70 17 set...
Copy-number variations (CNVs) are important in the aetiology of neurodevelopmental disorders and show broad phenotypic manifestations. We compared presence small CNVs disrupting ELP4-PAX6 locus 4,092 UK individuals with a range conditions, clinically referred for array comparative genomic hybridization, WTCCC controls (n = 4,783). The analysis was then extended using DECIPHER database. followed up association an autism patient cohort 3,143) six additional control groups 6,469). In clinical...
To identify shared genes and pathways between common absence epilepsy (AE) subtypes (childhood [CAE], juvenile [JAE], unclassified [UAE]) that may indicate mechanisms for seizure generation potentially a diagnostic continuum.We used high-density single-nucleotide polymorphism arrays to analyze genome-wide rare copy number variation (CNV) in cohort of 144 children with AEs (95 CAE, 26 UAE, 23 JAE).We identified CNVs are known risk factors AE 4 patients, including 3x 15q11.2 deletion. We also...
Sufficiently powered case-control studies with next-generation sequence (NGS) data remain prohibitively expensive for many investigators. If feasible, a more efficient strategy would be to include publicly available sequenced controls. However, these can confounded by differences in sequencing platform; alignment, single nucleotide polymorphism and variant calling algorithms; read depth; selection thresholds. Assuming one match cases controls on the basis of ethnicity other potential...
Objective Rolandic epilepsy is a common genetic focal of childhood characterized by centrotemporal sharp waves on electroencephalogram. In previous genome-wide analysis, we had reported linkage to chromosome 11p13, and fine mapping with 44 SNPs identified the ELP4-PAX6 locus in two independent US Canadian case–control samples. Here, aimed find causative variant for using larger sample higher resolution genotyping array. Methods We fine-mapped 186 individuals from rolandic families 1000...
Chondroadherin is a leucine-rich repeat protein known to mediate adhesion of isolated cells via the integrin α2β1 and interact with collagen. In this work, we show that cell chondroadherin leads activation MAPKs but does not result in spreading division. This contrast dividing grown on collagen, although binding mediated same receptor. We identified motif, CQLRGLRRWLEAK318 by mass spectrometry after protease digestion chondroadherin. Cells adhering synthetic peptide remained round, as was...
Background Rolandic epilepsy (RE) is the most common genetic childhood epilepsy, consisting of focal, nocturnal seizures and frequent neurodevelopmental impairments in speech, language, literacy attention. A complex aetiology presumed most, with monogenic mutations GRIN2A accounting for >5% cases. Objective To identify rare, causal CNV patients RE. Methods We used high-density SNP arrays to analyse presence rare CNVs 186 RE from UK, USA, Sardinia, Argentina Kerala, India. Results...
Despite the apparent robustness of language learning in humans, a large number children still fail to develop appropriate skills despite adequate means and opportunity. Most cases impairment have complex etiology, with genetic environmental influences. In contrast, we describe three‐generation German family who present an apparently simple segregation impairment. Investigations indicate auditory processing difficulties as core deficit. Affected members performed poorly on nonword repetition...
Background Reading disability (RD) is a common neurodevelopmental disorder with genetic basis established in families segregating "pure" dyslexia. RD commonly occurs disorders including Rolandic Epilepsy (RE), complex disorder. We performed genomewide linkage analysis of RE families, testing the hypotheses that genetically heterogenenous to pure dyslexia, and shares influences other sub-phenotypes RE. Methods initially genome-wide using 1000 STR markers 38 US ascertained through proband;...
Migraine headaches are a common comorbidity in Rolandic epilepsy ( RE ) and familial aggregation of migraine families suggests genetic basis not mediated by seizures. We performed genome‐wide linkage analysis the phenotype 38 with to localize potential contribution, follow‐up an additional 21 at linked loci. used two‐point multipoint LOD (logarithm odds) score methods for linkage, maximized over models. found evidence chromosome 17q12‐22 [multipoint HLOD (heterogeneity 4.40, recessive, 99%...