Abstract：
:Genome-wide association studies (GWASs) have been successful in detecting variants correlated with phenotypes of clinical interest. However, the power to detect these variants depends on the number of individuals whose phenotypes are collected, and for phenotypes that are difficult to collect, the sample size might be insufficient to achieve the desired statistical power. The phenotype of interest is often difficult to collect, whereas surrogate phenotypes or related phenotypes are easier to collect and have already been collected in very large samples. This paper demonstrates how we take advantage of these additional related phenotypes to impute the phenotype of interest or target phenotype and then perform association analysis. Our approach leverages the correlation structure between phenotypes to perform the imputation. The correlation structure can be estimated from a smaller complete dataset for which both the target and related phenotypes have been collected. Under some assumptions, the statistical power can be computed analytically given the correlation structure of the phenotypes used in imputation. In addition, our method can impute the summary statistic of the target phenotype as a weighted linear combination of the summary statistics of related phenotypes. Thus, our method is applicable to datasets for which we have access only to summary statistics and not to the raw genotypes. We illustrate our approach by analyzing associated loci to triglycerides (TGs), body mass index (BMI), and systolic blood pressure (SBP) in the Northern Finland Birth Cohort dataset.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Hormozdiari F,Kang EY,Bilow M,Ben-David E,Vulpe C,McLachlan S,Lusis AJ,Han B,Eskin Edoi
10.1016/j.ajhg.2016.04.013subject
Has Abstractpub_date
2016-07-07 00:00:00pages
89-103issue
1eissn
0002-9297issn
1537-6605pii
S0002-9297(16)30132-Xjournal_volume
99pub_type
杂志文章,meta分析abstract：:Over the past 20 years, the focus of national efforts to improve K-12 science education has ranged from curriculum and professional development of teachers to the adoption of science standards and high-stakes testing. In spite of this work, students in the United States continue to lag behind their peers in other coun...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2009.05.010
更新日期：2009-07-01 00:00:00
abstract：:Genetic hemochromatosis (GH) is believed to be a disease restricted to those of European ancestry. In northwestern Europe, >80% of GH patients are homozygous for one mutation, the substitution of tyrosine for cysteine at position 282 (C282Y) in the unprocessed protein. In a proportion of GH patients, two mutations are...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302318
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abstract：:The level of linkage disequilibrium between the XY275 MspI polymorphism and the X and Y boundaries was investigated in 21 different southern African populations. A full range of frequencies of the high allele was observed on the 1,013 X chromosomes studied, in keeping with published data. In previous studies fixation ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1992-06-01 00:00:00
abstract：:We have previously shown that rheumatoid arthritis (RA) risk alleles overlap between different ethnic groups. Here, we utilize a multiethnic approach to show that we can effectively discover RA risk alleles. Thirteen putatively associated SNPs that had not yet exceeded genome-wide significance (p < 5 × 10(-8)) in our ...
journal_title：American journal of human genetics
pub_type： 杂志文章,meta分析
doi：10.1016/j.ajhg.2012.01.010
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abstract：:The lymphatic vasculature is essential for the recirculation of extracellular fluid, fat absorption, and immune function and as a route of tumor metastasis. The dissection of molecular mechanisms underlying lymphangiogenesis has been accelerated by the identification of tissue-specific lymphatic endothelial markers an...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2010.08.008
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journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1981-09-01 00:00:00
abstract：:Hereditary fructose intolerance (HFI) is an inborn error of metabolism, inherited as an autosomal recessive disorder and caused by a decrease in the activity of fructose-1-phosphate aldolase (aldolase B) in affected individuals. Investigation of the molecular basis of HFI is reported here by the identification of two ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1990-06-01 00:00:00
abstract：:Microtubules are dynamic cytoskeletal elements coordinating and supporting a variety of neuronal processes, including cell division, migration, polarity, intracellular trafficking, and signal transduction. Mutations in genes encoding tubulins and microtubule-associated proteins are known to cause neurodevelopmental an...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2016.08.003
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journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1983-05-01 00:00:00
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journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1984-07-01 00:00:00
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journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2020.04.009
更新日期：2020-06-04 00:00:00
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journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1996-06-01 00:00:00
abstract：:We determined the mutation spectrum of the RP2 and RPGR genes in patients with X-linked retinitis pigmentosa (XLRP) and searched for correlations between categories of mutation and severity of disease. We screened 187 unrelated male patients for mutations, including 135 with a prior clinical diagnosis of XLRP, 11 with...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/379379
更新日期：2003-11-01 00:00:00
abstract：:The residual beta-D-galactosidase activity (10% of normal) present in an autopsy sample of liver derived from an I-cell patient has been characterized. The pH optima for both I-cell and normal acid 4-methylumbelliferyl beta-D-galactoside activities were 4.35. The adsorption and elution profiles of the I-cell enzyme fr...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1975-11-01 00:00:00
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journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302994
更新日期：2000-07-01 00:00:00
abstract：:Unbalanced Robertsonian translocations are a significant cause of mental retardation and fetal wastage. The majority of homologous rearrangements of chromosome 21 in Down syndrome have been shown to be isochromosomes. Aside from chromosome 21, very little is known about other acrocentric homologous rearrangements. In ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1994-11-01 00:00:00
abstract：:Living at high altitude is one of the most difficult challenges that humans had to cope with during their evolution. Whereas several genomic studies have revealed some of the genetic bases of adaptations in Tibetan, Andean, and Ethiopian populations, relatively little evidence of convergent evolution to altitude in di...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2014.09.002
更新日期：2014-10-02 00:00:00
abstract：:The extended Simes' test (known as GATES) and scaled chi-square test were proposed to combine a set of dependent genome-wide association signals at multiple single-nucleotide polymorphisms (SNPs) for assessing the overall significance of association at the gene or pathway levels. The two tests use different strategies...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2012.08.004
更新日期：2012-09-07 00:00:00
abstract：:The design and feasibility of whole-genome-association studies are critically dependent on the extent of linkage disequilibrium (LD) between markers. Although there has been extensive theoretical discussion of this, few empirical data exist. The authors have determined the extent of LD among 38 biallelic markers with ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/316906
更新日期：2000-12-01 00:00:00
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journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2010.01.027
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journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/301933
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journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/507652
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journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
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journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302062
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abstract：:Hereditary gingival fibromatosis (HGF) is a rare, autosomal dominant form of gingival overgrowth. Affected individuals have a benign, slowly progressive, nonhemorrhagic, fibrous enlargement of the oral masticatory mucosa. Genetic loci for autosomal dominant forms of HGF have been localized to chromosome 2p21-p22 (HGF1...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/339689
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abstract：:Osteogenesis imperfecta (OI) is a heritable disorder that ranges in severity from death in the perinatal period to an increased lifetime risk of fracture. Mutations in COL1A1 and COL1A2, which encode the chains of type I procollagen, result in dominant forms of OI, and mutations in several other genes result in recess...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2013.02.009
更新日期：2013-04-04 00:00:00
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journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1994-08-01 00:00:00
abstract：:The exploration of copy-number variation (CNV), notably of somatic cells, is an understudied aspect of genome biology. Any differences in the genetic makeup between twins derived from the same zygote represent an irrefutable example of somatic mosaicism. We studied 19 pairs of monozygotic twins with either concordant ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2007.12.011
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journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1991-11-01 00:00:00
abstract：:We present a systematic review of pleiotropy among SNPs and genes reported to show genome-wide association with common complex diseases and traits. We find abundant evidence of pleiotropy; 233 (16.9%) genes and 77 (4.6%) SNPs show pleiotropic effects. SNP pleiotropic status was associated with gene location (p = 0.024...
journal_title：American journal of human genetics
pub_type： 杂志文章,评审
doi：10.1016/j.ajhg.2011.10.004
更新日期：2011-11-11 00:00:00
