ArticleProceedings of the National Academy of Sciences of the United States of America2009
Systematic haplotype analysis resolves a complex plasma plant sterol locus on the Micronesian Island of Kosrae.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- Selecting Clustering Algorithms for Identity-By-Descent Mapping.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2023Article
- Deltapine 15 contributes to the genomic architecture of modern upland cotton cultivars.TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik · 2022Article
- Rapid detection of identity-by-descent tracts for mega-scale datasets.Nature communications · 2021Article
- A Fast and Simple Method for Detecting Identity-by-Descent Segments in Large-Scale Data.American journal of human genetics · 2020Article
- Article
- Parente2: a fast and accurate method for detecting identity by descent.Genome research · 2015Article
- Coherent somatic mutation in autoimmune disease.PloS one · 2014Review
- Melanesian blond hair is caused by an amino acid change in TYRP1.Science (New York, N.Y.) · 2012Article
- Identity by descent mapping of founder mutations in cancer using high-resolution tumor SNP data.PloS one · 2012Article
- Identifying disease mutations in genomic medicine settings: current challenges and how to accelerate progress.Genome medicine · 2012Review
- Identity-by-descent-based phasing and imputation in founder populations using graphical models.Genetic epidemiology · 2011Article
- Mechanisms and genetic determinants regulating sterol absorption, circulating LDL levels, and sterol elimination: implications for classification and disease risk.Journal of lipid research · 2011Review
- Haplotype phasing: existing methods and new developments.Nature reviews. Genetics · 2011Review
- DASH: a method for identical-by-descent haplotype mapping uncovers association with recent variation.American journal of human genetics · 2011Article
- Increased power of mixed models facilitates association mapping of 10 loci for metabolic traits in an isolated population.Human molecular genetics · 2011Article
- A fast, powerful method for detecting identity by descent.American journal of human genetics · 2011Article
- Single-tissue and cross-tissue heritability of gene expression via identity-by-descent in related or unrelated individuals.PLoS genetics · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pinpointing culprit causal variants along signal peaks of genome-wide association studies (GWAS) is challenging. To overcome confounding effects of multiple independent variants at such a locus and narrow the interval for causal allele capture, we developed an approach that maps local shared haplotypes harboring a putative causal variant. We demonstrate our method in an extreme isolate founder population, the pacific Island of Kosrae. We analyzed plasma plant sterol (PPS) levels, a surrogate measure of cholesterol absorption from the intestine, where previous studies have implicated 2p21 mutations in the ATP binding cassette subfamily G members 5 or 8 (ABCG5 or ABCG8) genes. We have previously reported that 11.1% of the islanders are carriers of a frameshift ABCG8 mutation increasing PPS levels in carriers by 50%. GWAS adjusted for this mutation revealed genomewide significant signals along 11 Mb around it. To fine-map this signal, we detected pairwise identity-by-descent haplotypes using our tool GERMLINE and implemented a clustering algorithm to identify haplotypes shared across multiple samples with their unique shared boundaries. A single 526-kb haplotype mapped strongly to PPS levels, dramatically refining the mapped interval. This haplotype spans the ABCG5/ABCG8 genes, is carried by 1.8% of the islanders, and results in a striking 100% increase of PPS in carriers. Resequencing of ABCG5 in these carriers found a D450H missense mutation along the associated haplotype. These findings exemplify the power of haplotype analysis for mapping mutations in isolated populations and specifically for dissecting effects of multiple variants of the same locus.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.