Abstract
Genome-wide association (GWA) studies represent a powerful strategy for identifying susceptibility genes for complex diseases in human populations but results must be confirmed and replicated. Because of the close homology between mouse and human genomes, the mouse can be used to add evidence to genes suggested by human studies. We used the mouse quantitative trait loci (QTL) map to interpret results from a GWA study for genes associated with plasma HDL cholesterol levels. We first positioned single nucleotide polymorphisms (SNPs) from a human GWA study on the genomic map for mouse HDL QTL. We then used mouse bioinformatics, sequencing, and expression studies to add evidence for one well-known HDL gene (Abca1) and three newly identified genes (Galnt2, Wwox, and Cdh13), thus supporting the results of the human study. For GWA peaks that occur in human haplotype blocks with multiple genes, we examined the homologous regions in the mouse to prioritize the genes using expression, sequencing, and bioinformatics from the mouse model, showing that some genes were unlikely candidates and adding evidence for candidate genes Mvk and Mmab in one haplotype block and Fads1 and Fads2 in the second haplotype block. Our study highlights the value of mouse genetics for evaluating genes found in human GWA studies.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1139-1149 |
| Number of pages | 11 |
| Journal | Journal of Lipid Research |
| Volume | 52 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 1 2011 |
| Externally published | Yes |
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Keywords
- Comparative genomics
- Genomics
- High density lipoprotein
- Mouse model
- Quantitative trait loci
ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Endocrinology
Cite this
The mouse QTL map helps interpret human genome-wide association studies for HDL cholesterol. / Leduc, Magalie S.; Lyons, Malcolm; Darvishi, Katayoon; Walsh, Kenneth; Sheehan, Susan; Amend, Sarah; Cox, Allison; Orho-Melander, Marju; Kathiresan, Sekar; Paigen, Beverly; Korstanje, Ron.
In: Journal of Lipid Research, Vol. 52, No. 6, 01.06.2011, p. 1139-1149.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The mouse QTL map helps interpret human genome-wide association studies for HDL cholesterol
AU - Leduc, Magalie S.
AU - Lyons, Malcolm
AU - Darvishi, Katayoon
AU - Walsh, Kenneth
AU - Sheehan, Susan
AU - Amend, Sarah
AU - Cox, Allison
AU - Orho-Melander, Marju
AU - Kathiresan, Sekar
AU - Paigen, Beverly
AU - Korstanje, Ron
PY - 2011/6/1
Y1 - 2011/6/1
N2 - Genome-wide association (GWA) studies represent a powerful strategy for identifying susceptibility genes for complex diseases in human populations but results must be confirmed and replicated. Because of the close homology between mouse and human genomes, the mouse can be used to add evidence to genes suggested by human studies. We used the mouse quantitative trait loci (QTL) map to interpret results from a GWA study for genes associated with plasma HDL cholesterol levels. We first positioned single nucleotide polymorphisms (SNPs) from a human GWA study on the genomic map for mouse HDL QTL. We then used mouse bioinformatics, sequencing, and expression studies to add evidence for one well-known HDL gene (Abca1) and three newly identified genes (Galnt2, Wwox, and Cdh13), thus supporting the results of the human study. For GWA peaks that occur in human haplotype blocks with multiple genes, we examined the homologous regions in the mouse to prioritize the genes using expression, sequencing, and bioinformatics from the mouse model, showing that some genes were unlikely candidates and adding evidence for candidate genes Mvk and Mmab in one haplotype block and Fads1 and Fads2 in the second haplotype block. Our study highlights the value of mouse genetics for evaluating genes found in human GWA studies.
AB - Genome-wide association (GWA) studies represent a powerful strategy for identifying susceptibility genes for complex diseases in human populations but results must be confirmed and replicated. Because of the close homology between mouse and human genomes, the mouse can be used to add evidence to genes suggested by human studies. We used the mouse quantitative trait loci (QTL) map to interpret results from a GWA study for genes associated with plasma HDL cholesterol levels. We first positioned single nucleotide polymorphisms (SNPs) from a human GWA study on the genomic map for mouse HDL QTL. We then used mouse bioinformatics, sequencing, and expression studies to add evidence for one well-known HDL gene (Abca1) and three newly identified genes (Galnt2, Wwox, and Cdh13), thus supporting the results of the human study. For GWA peaks that occur in human haplotype blocks with multiple genes, we examined the homologous regions in the mouse to prioritize the genes using expression, sequencing, and bioinformatics from the mouse model, showing that some genes were unlikely candidates and adding evidence for candidate genes Mvk and Mmab in one haplotype block and Fads1 and Fads2 in the second haplotype block. Our study highlights the value of mouse genetics for evaluating genes found in human GWA studies.
KW - Comparative genomics
KW - Genomics
KW - High density lipoprotein
KW - Mouse model
KW - Quantitative trait loci
UR - http://www.scopus.com/inward/record.url?scp=79955982125&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79955982125&partnerID=8YFLogxK
U2 - 10.1194/jlr.M009175
DO - 10.1194/jlr.M009175
M3 - Article
C2 - 21444760
AN - SCOPUS:79955982125
VL - 52
SP - 1139
EP - 1149
JO - Journal of Lipid Research
JF - Journal of Lipid Research
SN - 0022-2275
IS - 6
ER -