Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

Genome-wide association studies of coffee intake in UK/US participants of European ancestry uncover cohort-specific genetic associations

Coffee is one of the most widely consumed beverages. We performed a genome-wide association study (GWAS) of coffee intake in US-based 23andMe participants (N = 130,153) and identified 7 significant loci, with many replicating in three multi-ancestral cohorts. We examined genetic correlations and performed a phenome-wide association study across hundreds of biomarkers, health, and lifestyle traits, then compared our results to the largest available GWAS of coffee intake from the UK Biobank (UKB; N = 334,659). We observed consistent positive genetic correlations with substance use and obesity in both cohorts. Other genetic correlations were discrepant, including positive genetic correlations between coffee intake and psychiatric illnesses, pain, and gastrointestinal traits in 23andMe that were absent or negative in the UKB, and genetic correlations with cognition that were negative in 23andMe but positive in the UKB. Phenome-wide association study using polygenic scores of coffee intake derived from 23andMe or UKB summary statistics also revealed consistent associations with increased odds of obesity- and red blood cell-related traits, but all other associations were cohort-specific. Our study shows that the genetics of coffee intake associate with substance use and obesity across cohorts, but also that GWAS performed in different populations could capture cultural differences in the relationship between behavior and genetics.</p

Discovery of 42 genome-wide significant loci associated with dyslexia

Auteurs : 23andMe Research Team*, Quantitative Trait Working Group of the GenLang Consortium*International audienceReading and writing are crucial life skills but roughly one in ten children are affected by dyslexia, which can persist into adulthood. Family studies of dyslexia suggest heritability up to 70%, yet few convincing genetic markers have been found. Here we performed a genome-wide association study of 51,800 adults self-reporting a dyslexia diagnosis and 1,087,070 controls and identified 42 independent genome-wide significant loci: 15 in genes linked to cognitive ability/educational attainment, and 27 new and potentially more specific to dyslexia. We validated 23 loci (13 new) in independent cohorts of Chinese and European ancestry. Genetic etiology of dyslexia was similar between sexes, and genetic covariance with many traits was found, including ambidexterity, but n ot n eu ro an at omical measures of language-related circuitry. Dyslexia polygenic scores explained up to 6% of variance in reading traits, and might in future contribute to earlier identification and remediation of dyslexia. The ability to read is crucial for success at school and access to employment, information and health and social services, and is related to attained socioeconomic status 1. Dyslexia is a neurodevelopmental disorder characterized by severe reading difficulties, present in 5-17.5% of the population, depending on diagnostic criteria 2,3. It often involves impaired phonological processing (the decoding of sound units, or phonemes, within words) and frequently co-occurs with psychiatric and other developmental disorders 4 , especially attention-deficit hyperactivity disorde

Discovery of 42 genome-wide significant loci associated with dyslexia

AbstractReading and writing are crucial life skills but roughly one in ten children are affected by dyslexia, which can persist into adulthood. Family studies of dyslexia suggest heritability up to 70%, yet few convincing genetic markers have been found. Here we performed a genome-wide association study of 51,800 adults self-reporting a dyslexia diagnosis and 1,087,070 controls and identified 42 independent genome-wide significant loci: 15 in genes linked to cognitive ability/educational attainment, and 27 new and potentially more specific to dyslexia. We validated 23 loci (13 new) in independent cohorts of Chinese and European ancestry. Genetic etiology of dyslexia was similar between sexes, and genetic covariance with many traits was found, including ambidexterity, but not neuroanatomical measures of language-related circuitry. Dyslexia polygenic scores explained up to 6% of variance in reading traits, and might in future contribute to earlier identification and remediation of dyslexia.</jats:p

Multi-ancestry genome-wide association meta-analysis of Parkinson’s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations