Alisa K. Manning
A5036685109- Genetic Associations and Epidemiology
- Nutrition, Genetics, and Disease
- Bioinformatics and Genomic Networks
- Genetic Mapping and Diversity in Plants and Animals
- Epigenetics and DNA Methylation
- Liver Disease Diagnosis and Treatment
- Genomics and Rare Diseases
- Pancreatic function and diabetes
- Birth, Development, and Health
- RNA modifications and cancer
- Diabetes and associated disorders
- Diet and metabolism studies
- Genetic and phenotypic traits in livestock
- Cancer-related gene regulation
- Diet, Metabolism, and Disease
- Metabolomics and Mass Spectrometry Studies
- Metabolism, Diabetes, and Cancer
- Cancer Genomics and Diagnostics
- Cancer-related molecular mechanisms research
- Gene expression and cancer classification
- Acute Myeloid Leukemia Research
- RNA Research and Splicing
- Nutritional Studies and Diet
- Cardiovascular Health and Risk Factors
- Diabetes Management and Research
Massachusetts General Hospital
2016-2025
Harvard University
2016-2025
Broad Institute
2016-2025
Lehigh University
2024
Boston University
2007-2023
Center for Human Genetics
2015-2023
Providence College
2021-2023
Universidad de Zaragoza
2023
Massachusetts Institute of Technology
2014-2021
Global Cancer Institute
2021
The incidence of hematologic cancers increases with age. These are associated recurrent somatic mutations in specific genes. We hypothesized that such would be detectable the blood some persons who not known to have disorders.
Age-related macular degeneration (AMD) is a common, late-onset, and complex trait with multiple risk factors. Concentrating on region harboring locus for AMD 1q25-31, the ARMD1 locus, we tested single-nucleotide polymorphisms association in two independent case-control populations. Significant ( P = 4.95 × 10 -10 ) was identified within regulation of complement activation centered over tyrosine-402 → histidine-402 protein polymorphism gene encoding factor H. Possession at least one histidine...
Multiple genetic loci have been convincingly associated with the risk of type 2 diabetes mellitus. We tested hypothesis that knowledge these allows better prediction than common phenotypic factors alone.
Exome sequencing studies in complex diseases are challenged by the allelic heterogeneity, large number and modest effect sizes of associated variants on disease risk presence numbers neutral variants, even phenotypically relevant genes. Isolated populations with recent bottlenecks offer advantages for studying rare as they have deleterious that present at higher frequencies well a substantial reduction variation. To explore potential Finnish founder population low-frequency (0.5–5%)...
Abstract Background Blood lipid levels including low-density lipoprotein cholesterol (LDL-C), high-density (HDL-C), and triglycerides (TG) are highly heritable. Genome-wide association is a promising approach to map genetic loci related these heritable phenotypes. Methods In 1087 Framingham Heart Study Offspring cohort participants (mean age 47 years, 52% women), we conducted genome-wide analyses (Affymetrix 100K GeneChip) for fasting blood traits. Total cholesterol, HDL-C, TG were measured...
Protein-coding genetic variants that strongly affect disease risk can yield relevant clues to pathogenesis. Here we report exome-sequencing analyses of 20,791 individuals with type 2 diabetes (T2D) and 24,440 non-diabetic control participants from 5 ancestries. We identify gene-level associations rare (with minor allele frequencies less than 0.5%) in 4 genes at exome-wide significance, including a series more 30 SLC30A8 alleles conveys protection against T2D, 12 gene sets, those...
Common diseases such as type 2 diabetes are phenotypically heterogeneous. Obesity is a major risk factor for diabetes, but patients vary appreciably in body mass index. We hypothesized that the genetic predisposition to disease may be different lean (BMI<25 Kg/m²) compared obese cases (BMI≥30 Kg/m²). performed two case-control genome-wide studies using accepted cut-offs defining individuals overweight or obese. used 2,112 kg/m²) 4,123 kg/m²), and 54,412 un-stratified controls. Replication...
Summary paragraph The Trans-Omics for Precision Medicine (TOPMed) program seeks to elucidate the genetic architecture and disease biology of heart, lung, blood, sleep disorders, with ultimate goal improving diagnosis, treatment, prevention. initial phases focus on whole genome sequencing individuals rich phenotypic data diverse backgrounds. Here, we describe TOPMed goals design as well resources early insights from sequence data. include a variant browser, genotype imputation panel, sharing...
The Framingham Heart Study (FHS), founded in 1948 to examine the epidemiology of cardiovascular disease, is among most comprehensively characterized multi-generational studies world. Many collected phenotypes have substantial genetic contributors; yet determinants remain be identified. Using single nucleotide polymorphisms (SNPs) from a 100K genome-wide scan, we associations common with phenotypic variation this community-based cohort and provide full-disclosure, web-based resource results...
Elevated plasma concentrations of HDL cholesterol (HDL-C) are associated with protection from atherosclerotic cardiovascular disease. Animal models indicate that decreased expression endothelial lipase (LIPG) is inversely HDL-C levels, and genome-wide association studies have identified LIPG variants as being levels in humans. We hypothesized loss-of-function mutations may result elevated therefore performed deep resequencing exons cases controls levels. a significant excess nonsynonymous...
Summary Meta‐analysis is a powerful approach to combine evidence from multiple studies make inference about one or more parameters of interest, such as regression coefficients. The validity the fixed effect model meta‐analysis depends on underlying assumption that all in share same size. In presence heterogeneity, incorrectly ignores between‐study variance and may yield false positive results. random takes into account both within‐study variances. It conservative than should be favored...
Genetic discoveries are validated through the meta-analysis of genome-wide association scans in large international consortia. Because environmental variables may interact with genetic factors, investigation differing effects for distinct levels an exposure these consortia yield additional susceptibility loci undetected by main analysis. We describe a method joint (JMA) SNP and Environment (SNP × E) regression coefficients use gene-environment interaction studies.
To test if knowledge of type 2 diabetes genetic variants improves disease prediction.We tested 40 single nucleotide polymorphisms (SNPs) associated with in 3,471 Framingham Offspring Study subjects followed over 34 years using pooled logistic regression models stratified by age (<50 years, cases = 144; or ≥50 302). Models included clinical risk factors and a 40-SNP weighted score.In people <50 age, the model C-statistic was 0.908; score increased it to 0.911 (P 0.3; net reclassification...
Deep sequence-based imputation can enhance the discovery power of genome-wide association studies by assessing previously unexplored variation across common- and low-frequency spectra. We applied a hybrid whole-genome sequencing (WGS) deep approach to examine broader allelic architecture 12 anthropometric traits associated with height, body mass, fat distribution in up 267,616 individuals. report 106 significant signals that have not been identified, including 9 variants pointing functional...