The mouse QTL map helps interpret human genome-wide association studies for HDL cholesterol

Leduc, Magalie S.; Lyons, Malcolm A.; Darvishi, Katayoon; Walsh, Kenneth A.; Sheehan, Susan; Amend, Sarah R.; Cox, Allison; Orho‐Melander, Marju; Kathiresan, Sekar; Paigen, Beverly; Korstanje, Ron

doi:10.1194/jlr.m009175

Cited by 28 publications

(30 citation statements)

References 49 publications

(52 reference statements)

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“…Abca1 has been identifi ed as the QTL gene in four other crosses by our laboratory, based on a difference in expression or a nonsynonymous coding polymorphism ( 8 ). Resequencing verifi ed that the damaging polymorphism did not segregate between MRL and SM (data not shown).…”

Section: Genomic Dissection Of the Hdl Qtl Based On Bioinformaticsmentioning

confidence: 99%

“…This latter fi nding may indicate a difference in the genetics of HDL metabolism between mice and humans. However, our group has previously shown that genes regulating HDL-cholesterol are often concordant between mice and humans ( 7,8 ). Mouse intercrosses allow for the identifi cation of QTL due to a specifi c strain's polymorphisms that have an effect strong enough to be detectable in the F2 population studied.…”

Section: Note Added In Proofmentioning

confidence: 99%

“…To date, our laboratory and those of others have identifi ed over 35 mouse HDL QTL (as reviewed in Wang et al, Refs. 7,8 ). In addition, we and others have developed bioinformatics tools to narrow the QTL interval to just a few candidate genes ( 9, 10 ).…”

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confidence: 99%

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Using bioinformatics and systems genetics to dissect HDL-cholesterol genetics in an MRL/MpJ × SM/J intercross

Leduc

Blair

Verdugo

et al. 2012

Journal of Lipid Research

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A higher incidence of coronary artery disease (CAD) is associated with a lower level of HDL-cholesterol ( 1, 2 ), which is determined by multiple environmental and genetic factors. In the past few years, new therapeutic approaches have focused on fi nding ways to increase HDL ( 3, 4 ). To date, however, only a few environmental interventions, such as diet and exercise, have been successful in raising HDL level ( 5 ), whereas drug therapy development is still ongoing and has targeted only a limited number of proteins such as CETP ( 3, 4 ). In the search for a potential drug target to raise HDL and decrease CAD, the identifi cation of new genes involved in HDL determination is essential.The genetic basis of HDL-cholesterol variation has been widely studied in various animal models. In humans, recent genome-wide association studies (GWAS) have identifi ed known HDL genes such as LIPG and CETP in addition to new genes such as GALNT2 ( 6 ). These known genes, however, explain only a small proportion of the total variation, indicating that additional genes are yet to be discovered. Mouse models are a powerful strategy for identifying such genes. A large overlap exists among species for quantitative trait loci (QTL) and genes involved in lipid metabolism ( 7 ). Many study methodologies are similar between human and mouse, but mouse studies offer advantages by capitalizing on genomics tools that are not available and practical for studies of human populations. To date, our laboratory and those of others have identifi ed over 35 mouse HDL QTL (as reviewed in Wang et al., Refs. 7,8 ). In addition, we and others have developed bioinformatics tools to narrow the QTL interval to just a few candidate genes ( 9, 10 ). Application of these tools has led to the discovery of single genes underlying QTL for HDL and

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Section: Genomic Dissection Of the Hdl Qtl Based On Bioinformaticsmentioning

confidence: 99%

Section: Note Added In Proofmentioning

confidence: 99%

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Using bioinformatics and systems genetics to dissect HDL-cholesterol genetics in an MRL/MpJ × SM/J intercross

Leduc

Blair

Verdugo

et al. 2012

Journal of Lipid Research

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“…Three recent studies demonstrated that WWOX gene is associated with the alterations of plasma HDL levels Sáez et al, 2010;Leduc et al, 2011). By genotyping of single nucleotide polymorphisms (SNPs), Lee et al identified one SNP, rs2548861, in the intron 8 of WWOX gene with region-wide significance for low HDL-C in dyslipidemic families of Mexican and European descent and in low-HDL-C cases and controls of European descent.…”

Section: Complement Protein C1q As An Activator Of Wwox/wox1mentioning

confidence: 99%

“…They concluded that there is a significant association between HDL-C and a WWOX variant with an allele-specific cis-regulatory function. Similar approaches, coupled with mouse genome mapping, were also used to indicate the association of WWOX gene with HDL cholesterol and triglyceride levels (Sáez et al, 2010;Leduc et al, 2011).…”

Section: Complement Protein C1q As An Activator Of Wwox/wox1mentioning

confidence: 99%

WW Domain-Containing Oxidoreductase is a Potential Receptor for Sex Steroid Hormones

Su¹,

Chen²,

Chen³

et al. 2012

Sex Hormones

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Molecular Genetics of Bipolar Disorder

Offord

2013

Encyclopedia of Life Sciences

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Bipolar disorder (BPD) is a disease of unknown etiology, which is a major cause of disability. The disease is characterised by oscillation between a manic state and a depressed state, and has a significant genetic component. To try to improve understanding of the disease, linkage studies and association studies have been conducted on bipolar subjects. To date these studies have yielded equivocal results. A very small number of genomic regions and genes have been identified which are associated with the bipolar disease. This small number of genes does not explain the high heritability of the disease. Using the results of these screens as starting points it should prove possible to develop a model for the underlying molecular components of BPD. Key Concepts: Bipolar disorder is a highly heritable psychiatric disorder where genetics are proving to be complex. Psychiatric linkage studies have been less successful than genome wide association studies at showing involvement of genes in psychiatric disease. Genome wide association studies can provide information about genes that are involved in a disorder. Not all of the heritability of bipolar disorder has been explained by genetic association studies. The nature of this ‘missing heritability’ remains unclear. Genetic modifiers are genes that can alter the phenotype caused by a mutation. These genetic modifiers may account for some of the missing heritability seen in bipolar disorder.

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The mouse QTL map helps interpret human genome-wide association studies for HDL cholesterol

Cited by 28 publications

References 49 publications

Using bioinformatics and systems genetics to dissect HDL-cholesterol genetics in an MRL/MpJ × SM/J intercross

Using bioinformatics and systems genetics to dissect HDL-cholesterol genetics in an MRL/MpJ × SM/J intercross

WW Domain-Containing Oxidoreductase is a Potential Receptor for Sex Steroid Hormones

Molecular Genetics of Bipolar Disorder

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