Research papers
2015 · Nature · 20,291 citations
The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies. Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics. The 1000 Genomes Project has sought to comprehensively catalogue human genetic variation across populations, providing a valuable public genomic resource. The data obtained so far have found applications ranging from association studies and fine mapping studies to the filtering of likely neutral variants in rare-disease cohorts. The authors now report on the final phase of the project, phase 3, which covers previously uncharacterized areas of human genetic diversity in terms of the populations sampled and categories of characterized variation. The sample now includes more than 2,500 individuals from 26 global populations, with low coverage whole-genome and deep exome sequencing, as well as dense microarray genotyping. They find that while most common variants are shared across populations, rarer variants are often restricted to closely related populations. The authors also demonstrate the use of the phase 3 dataset as a reference panel for imputation to improve the resolution in genetic association studies.
2003 · Nature · 6,188 citations
The goal of the International HapMap Project is to determine the common patterns of DNA sequence variation in the human genome and to make this information freely available in the public domain. An international consortium is developing a map of these patterns across the genome by determining the genotypes of one million or more sequence variants, their frequencies and the degree of association between them, in DNA samples from populations with ancestry from parts of Africa, Asia and Europe. The HapMap will allow the discovery of sequence variants that affect common disease, will facilitate development of diagnostic tools, and will enhance our ability to choose targets for therapeutic intervention.
2022 · Nature · 2,848 citations
Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies. A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.
2021 · International Journal of Africa Nursing Sciences · 22 citations
Genetic nursing education provides knowledge of traits and inherited diseases. This has not been well integrated into nursing practice in Nigeria. This study evaluated university nursing students’ knowledge of genomic concepts and readiness to practice genomic nursing in Nigeria. A cross-sectional study was conducted. Three universities were purposively selected in Nigeria. A total of 136 participants were recruited using convenient sampling technique. A modified Genetic Nursing Concept Inventory questionnaire was distributed to participants in their classrooms. Data were analyzed with SPSS (23); descriptive data were presented in tables and figures with their mean and standard deviations. Chi-square test and multivariate analysis were used to ascertain association between variables at p < 0.05 level of significance. Findings indicated that participants have poor knowledge (89%) and lack readiness (66%) to practice genomic nursing in Nigeria. Their knowledge influenced their readiness (χ2 = 21.033, df = 1, p = 0.001). Institution type was the most consistent predictor of knowledge (χ2 = 48.586, df = 2, p = 0.001) and readiness (OR = 14.817, p = 0.326, C.I. = 3.190, 319.57) as those in federal institution were more knowledgeable and prepared to practice genetic nursing. Participants perceived that poor funding, lack of trained personnel, and social/environmental factors could affect their readiness to practice genetic nursing. The study has brought to the fore that nursing students have low knowledge and were not ready to practice genetic nursing, efforts should be made to look into the adequacy of nursing training on genetic nursing and strategies needed for its integration in education and practice.