Transferability and fine-mapping of genome-wide associated loci for adult height across human populations.
Human height is the prototypical polygenic quantitative trait. Recently, several genetic variants influencing adult height were identified, primarily in individuals of East Asian (Chinese Han or Korean) or European ancestry. Here, we examined 152 genetic variants representing 107 independent loci pr...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2009-12-01
|
| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20027299/pdf/?tool=EBI |
| _version_ | 1818744344534843392 |
|---|---|
| author | Daniel Shriner Adebowale Adeyemo Norman P Gerry Alan Herbert Guanjie Chen Ayo Doumatey Hanxia Huang Jie Zhou Michael F Christman Charles N Rotimi |
| author_facet | Daniel Shriner Adebowale Adeyemo Norman P Gerry Alan Herbert Guanjie Chen Ayo Doumatey Hanxia Huang Jie Zhou Michael F Christman Charles N Rotimi |
| author_sort | Daniel Shriner |
| collection | DOAJ |
| description | Human height is the prototypical polygenic quantitative trait. Recently, several genetic variants influencing adult height were identified, primarily in individuals of East Asian (Chinese Han or Korean) or European ancestry. Here, we examined 152 genetic variants representing 107 independent loci previously associated with adult height for transferability in a well-powered sample of 1,016 unrelated African Americans. When we tested just the reported variants originally identified as associated with adult height in individuals of East Asian or European ancestry, only 8.3% of these loci transferred (p-values < or =0.05 under an additive genetic model with directionally consistent effects) to our African American sample. However, when we comprehensively evaluated all HapMap variants in linkage disequilibrium (r(2) > or = 0.3) with the reported variants, the transferability rate increased to 54.1%. The transferability rate was 70.8% for associations originally reported as genome-wide significant and 38.0% for associations originally reported as suggestive. An additional 23 loci were significantly associated but failed to transfer because of directionally inconsistent effects. Six loci were associated with adult height in all three groups. Using differences in linkage disequilibrium patterns between HapMap CEU or CHB reference data and our African American sample, we fine-mapped these six loci, improving both the localization and the annotation of these transferable associations. |
| first_indexed | 2024-12-18T02:42:49Z |
| format | Article |
| id | doaj.art-2946079f73ef4dcebe17e2658c806f5e |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-18T02:42:49Z |
| publishDate | 2009-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-2946079f73ef4dcebe17e2658c806f5e2022-12-21T21:23:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-12-01412e839810.1371/journal.pone.0008398Transferability and fine-mapping of genome-wide associated loci for adult height across human populations.Daniel ShrinerAdebowale AdeyemoNorman P GerryAlan HerbertGuanjie ChenAyo DoumateyHanxia HuangJie ZhouMichael F ChristmanCharles N RotimiHuman height is the prototypical polygenic quantitative trait. Recently, several genetic variants influencing adult height were identified, primarily in individuals of East Asian (Chinese Han or Korean) or European ancestry. Here, we examined 152 genetic variants representing 107 independent loci previously associated with adult height for transferability in a well-powered sample of 1,016 unrelated African Americans. When we tested just the reported variants originally identified as associated with adult height in individuals of East Asian or European ancestry, only 8.3% of these loci transferred (p-values < or =0.05 under an additive genetic model with directionally consistent effects) to our African American sample. However, when we comprehensively evaluated all HapMap variants in linkage disequilibrium (r(2) > or = 0.3) with the reported variants, the transferability rate increased to 54.1%. The transferability rate was 70.8% for associations originally reported as genome-wide significant and 38.0% for associations originally reported as suggestive. An additional 23 loci were significantly associated but failed to transfer because of directionally inconsistent effects. Six loci were associated with adult height in all three groups. Using differences in linkage disequilibrium patterns between HapMap CEU or CHB reference data and our African American sample, we fine-mapped these six loci, improving both the localization and the annotation of these transferable associations.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20027299/pdf/?tool=EBI |
| spellingShingle | Daniel Shriner Adebowale Adeyemo Norman P Gerry Alan Herbert Guanjie Chen Ayo Doumatey Hanxia Huang Jie Zhou Michael F Christman Charles N Rotimi Transferability and fine-mapping of genome-wide associated loci for adult height across human populations. PLoS ONE |
| title | Transferability and fine-mapping of genome-wide associated loci for adult height across human populations. |
| title_full | Transferability and fine-mapping of genome-wide associated loci for adult height across human populations. |
| title_fullStr | Transferability and fine-mapping of genome-wide associated loci for adult height across human populations. |
| title_full_unstemmed | Transferability and fine-mapping of genome-wide associated loci for adult height across human populations. |
| title_short | Transferability and fine-mapping of genome-wide associated loci for adult height across human populations. |
| title_sort | transferability and fine mapping of genome wide associated loci for adult height across human populations |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20027299/pdf/?tool=EBI |
| work_keys_str_mv | AT danielshriner transferabilityandfinemappingofgenomewideassociatedlociforadultheightacrosshumanpopulations AT adebowaleadeyemo transferabilityandfinemappingofgenomewideassociatedlociforadultheightacrosshumanpopulations AT normanpgerry transferabilityandfinemappingofgenomewideassociatedlociforadultheightacrosshumanpopulations AT alanherbert transferabilityandfinemappingofgenomewideassociatedlociforadultheightacrosshumanpopulations AT guanjiechen transferabilityandfinemappingofgenomewideassociatedlociforadultheightacrosshumanpopulations AT ayodoumatey transferabilityandfinemappingofgenomewideassociatedlociforadultheightacrosshumanpopulations AT hanxiahuang transferabilityandfinemappingofgenomewideassociatedlociforadultheightacrosshumanpopulations AT jiezhou transferabilityandfinemappingofgenomewideassociatedlociforadultheightacrosshumanpopulations AT michaelfchristman transferabilityandfinemappingofgenomewideassociatedlociforadultheightacrosshumanpopulations AT charlesnrotimi transferabilityandfinemappingofgenomewideassociatedlociforadultheightacrosshumanpopulations |