Gene-based sequencing identifies lipid-influencing variants with ethnicity-specific effects in African Americans.
Although a considerable proportion of serum lipids loci identified in European ancestry individuals (EA) replicate in African Americans (AA), interethnic differences in the distribution of serum lipids suggest that some genetic determinants differ by ethnicity. We conducted a comprehensive evaluatio...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-03-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1004190 |
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| author | Amy R Bentley Guanjie Chen Daniel Shriner Ayo P Doumatey Jie Zhou Hanxia Huang James C Mullikin Robert W Blakesley Nancy F Hansen Gerard G Bouffard Praveen F Cherukuri Baishali Maskeri Alice C Young Adebowale Adeyemo Charles N Rotimi |
| author_facet | Amy R Bentley Guanjie Chen Daniel Shriner Ayo P Doumatey Jie Zhou Hanxia Huang James C Mullikin Robert W Blakesley Nancy F Hansen Gerard G Bouffard Praveen F Cherukuri Baishali Maskeri Alice C Young Adebowale Adeyemo Charles N Rotimi |
| author_sort | Amy R Bentley |
| collection | DOAJ |
| description | Although a considerable proportion of serum lipids loci identified in European ancestry individuals (EA) replicate in African Americans (AA), interethnic differences in the distribution of serum lipids suggest that some genetic determinants differ by ethnicity. We conducted a comprehensive evaluation of five lipid candidate genes to identify variants with ethnicity-specific effects. We sequenced ABCA1, LCAT, LPL, PON1, and SERPINE1 in 48 AA individuals with extreme serum lipid concentrations (high HDLC/low TG or low HDLC/high TG). Identified variants were genotyped in the full population-based sample of AA (n = 1694) and tested for an association with serum lipids. rs328 (LPL) and correlated variants were associated with higher HDLC and lower TG. Interestingly, a stronger effect was observed on a "European" vs. "African" genetic background at this locus. To investigate this effect, we evaluated the region among West Africans (WA). For TG, the effect size among WA was the same in AA with only African local ancestry (2-3% lower TG), while the larger association among AA with local European ancestry matched previous reports in EA (10%). For HDLC, there was no association with rs328 in AA with only African local ancestry or in WA, while the association among AA with European local ancestry was much greater than what has been observed for EA (15 vs. ∼ 5 mg/dl), suggesting an interaction with an environmental or genetic factor that differs by ethnicity. Beyond this ancestry effect, the importance of African ancestry-focused, sequence-based work was also highlighted by serum lipid associations of variants that were in higher frequency (or present only) among those of African ancestry. By beginning our study with the sequence variation present in AA individuals, investigating local ancestry effects, and seeking replication in WA, we were able to comprehensively evaluate the role of a set of candidate genes in serum lipids in AA. |
| format | Article |
| id | doaj-art-a6ff9c59fd2b4be3a0fefce070b59727 |
| institution | DOAJ |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2014-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-a6ff9c59fd2b4be3a0fefce070b597272025-08-20T03:10:05ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042014-03-01103e100419010.1371/journal.pgen.1004190Gene-based sequencing identifies lipid-influencing variants with ethnicity-specific effects in African Americans.Amy R BentleyGuanjie ChenDaniel ShrinerAyo P DoumateyJie ZhouHanxia HuangJames C MullikinRobert W BlakesleyNancy F HansenGerard G BouffardPraveen F CherukuriBaishali MaskeriAlice C YoungAdebowale AdeyemoCharles N RotimiAlthough a considerable proportion of serum lipids loci identified in European ancestry individuals (EA) replicate in African Americans (AA), interethnic differences in the distribution of serum lipids suggest that some genetic determinants differ by ethnicity. We conducted a comprehensive evaluation of five lipid candidate genes to identify variants with ethnicity-specific effects. We sequenced ABCA1, LCAT, LPL, PON1, and SERPINE1 in 48 AA individuals with extreme serum lipid concentrations (high HDLC/low TG or low HDLC/high TG). Identified variants were genotyped in the full population-based sample of AA (n = 1694) and tested for an association with serum lipids. rs328 (LPL) and correlated variants were associated with higher HDLC and lower TG. Interestingly, a stronger effect was observed on a "European" vs. "African" genetic background at this locus. To investigate this effect, we evaluated the region among West Africans (WA). For TG, the effect size among WA was the same in AA with only African local ancestry (2-3% lower TG), while the larger association among AA with local European ancestry matched previous reports in EA (10%). For HDLC, there was no association with rs328 in AA with only African local ancestry or in WA, while the association among AA with European local ancestry was much greater than what has been observed for EA (15 vs. ∼ 5 mg/dl), suggesting an interaction with an environmental or genetic factor that differs by ethnicity. Beyond this ancestry effect, the importance of African ancestry-focused, sequence-based work was also highlighted by serum lipid associations of variants that were in higher frequency (or present only) among those of African ancestry. By beginning our study with the sequence variation present in AA individuals, investigating local ancestry effects, and seeking replication in WA, we were able to comprehensively evaluate the role of a set of candidate genes in serum lipids in AA.https://doi.org/10.1371/journal.pgen.1004190 |
| spellingShingle | Amy R Bentley Guanjie Chen Daniel Shriner Ayo P Doumatey Jie Zhou Hanxia Huang James C Mullikin Robert W Blakesley Nancy F Hansen Gerard G Bouffard Praveen F Cherukuri Baishali Maskeri Alice C Young Adebowale Adeyemo Charles N Rotimi Gene-based sequencing identifies lipid-influencing variants with ethnicity-specific effects in African Americans. PLoS Genetics |
| title | Gene-based sequencing identifies lipid-influencing variants with ethnicity-specific effects in African Americans. |
| title_full | Gene-based sequencing identifies lipid-influencing variants with ethnicity-specific effects in African Americans. |
| title_fullStr | Gene-based sequencing identifies lipid-influencing variants with ethnicity-specific effects in African Americans. |
| title_full_unstemmed | Gene-based sequencing identifies lipid-influencing variants with ethnicity-specific effects in African Americans. |
| title_short | Gene-based sequencing identifies lipid-influencing variants with ethnicity-specific effects in African Americans. |
| title_sort | gene based sequencing identifies lipid influencing variants with ethnicity specific effects in african americans |
| url | https://doi.org/10.1371/journal.pgen.1004190 |
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