Abstract
Despite the substantial burden of hypertension in US minority populations, few genetic studies of blood pressure have been conducted in Hispanics and African Americans, and it is unclear whether many of the established loci identified in European-descent populations contribute to blood pressure variation in non-European descent populations. Using the Metabochip array, we sought to characterize the genetic architecture of previously identified blood pressure loci, and identify novel cardiometabolic variants related to systolic and diastolic blood pressure in a multi-ethnic US population including Hispanics (n = 19,706) and African Americans (n = 18,744). Several known blood pressure loci replicated in African Americans and Hispanics. Fourteen variants in three loci (KCNK3, FGF5, ATXN2-SH2B3) were significantly associated with blood pressure in Hispanics. The most significant diastolic blood pressure variant identified in our analysis, rs2586886/KCNK3 (P = 5.2 × 10-9), also replicated in independent Hispanic and European-descent samples. African American and trans-ethnic meta-analysis data identified novel variants in the FGF5, ULK4 and HOXA-EVX1 loci, which have not been previously associated with blood pressure traits. Our identification and independent replication of variants in KCNK3, a gene implicated in primary hyperaldosteronism, as well as a variant in HOTTIP (HOXA-EVX1) suggest that further work to clarify the roles of these genes may be warranted. Overall, our findings suggest that loci identified in European descent populations also contribute to blood pressure variation in diverse populations including Hispanics and African Americans - populations that are understudied for hypertension genetic risk factors.
| Original language | English (US) |
|---|---|
| Article number | e0164132 |
| Journal | PLoS One |
| Volume | 11 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 1 2016 |
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ASJC Scopus subject areas
- Medicine(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)
Cite this
Variant discovery and fine mapping of genetic loci associated with blood pressure traits in Hispanics and African Americans. / Franceschini, Nora; Carty, Cara L.; Lu, Yingchang; Tao, Ran; Sung, Yun Ju; Manichaikul, Ani; Haessler, Jeff; Fornage, Myriam; Schwander, Karen; Zubair, Niha; Bien, Stephanie; Hindorff, Lucia A.; Guo, Xiuqing; Bielinski, Suzette J; Ehret, Georg; Kaufman, Joel D.; Rich, Stephen S.; Carlson, Christopher S.; Bottinger, Erwin P.; North, Kari E.; Rao, D. C.; Chakravarti, Aravinda; Barrett, Paula Q.; Loos, Ruth J F; Buyske, Steven; Kooperberg, Charles.
In: PLoS One, Vol. 11, No. 10, e0164132, 01.10.2016.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Variant discovery and fine mapping of genetic loci associated with blood pressure traits in Hispanics and African Americans
AU - Franceschini, Nora
AU - Carty, Cara L.
AU - Lu, Yingchang
AU - Tao, Ran
AU - Sung, Yun Ju
AU - Manichaikul, Ani
AU - Haessler, Jeff
AU - Fornage, Myriam
AU - Schwander, Karen
AU - Zubair, Niha
AU - Bien, Stephanie
AU - Hindorff, Lucia A.
AU - Guo, Xiuqing
AU - Bielinski, Suzette J
AU - Ehret, Georg
AU - Kaufman, Joel D.
AU - Rich, Stephen S.
AU - Carlson, Christopher S.
AU - Bottinger, Erwin P.
AU - North, Kari E.
AU - Rao, D. C.
AU - Chakravarti, Aravinda
AU - Barrett, Paula Q.
AU - Loos, Ruth J F
AU - Buyske, Steven
AU - Kooperberg, Charles
PY - 2016/10/1
Y1 - 2016/10/1
N2 - Despite the substantial burden of hypertension in US minority populations, few genetic studies of blood pressure have been conducted in Hispanics and African Americans, and it is unclear whether many of the established loci identified in European-descent populations contribute to blood pressure variation in non-European descent populations. Using the Metabochip array, we sought to characterize the genetic architecture of previously identified blood pressure loci, and identify novel cardiometabolic variants related to systolic and diastolic blood pressure in a multi-ethnic US population including Hispanics (n = 19,706) and African Americans (n = 18,744). Several known blood pressure loci replicated in African Americans and Hispanics. Fourteen variants in three loci (KCNK3, FGF5, ATXN2-SH2B3) were significantly associated with blood pressure in Hispanics. The most significant diastolic blood pressure variant identified in our analysis, rs2586886/KCNK3 (P = 5.2 × 10-9), also replicated in independent Hispanic and European-descent samples. African American and trans-ethnic meta-analysis data identified novel variants in the FGF5, ULK4 and HOXA-EVX1 loci, which have not been previously associated with blood pressure traits. Our identification and independent replication of variants in KCNK3, a gene implicated in primary hyperaldosteronism, as well as a variant in HOTTIP (HOXA-EVX1) suggest that further work to clarify the roles of these genes may be warranted. Overall, our findings suggest that loci identified in European descent populations also contribute to blood pressure variation in diverse populations including Hispanics and African Americans - populations that are understudied for hypertension genetic risk factors.
AB - Despite the substantial burden of hypertension in US minority populations, few genetic studies of blood pressure have been conducted in Hispanics and African Americans, and it is unclear whether many of the established loci identified in European-descent populations contribute to blood pressure variation in non-European descent populations. Using the Metabochip array, we sought to characterize the genetic architecture of previously identified blood pressure loci, and identify novel cardiometabolic variants related to systolic and diastolic blood pressure in a multi-ethnic US population including Hispanics (n = 19,706) and African Americans (n = 18,744). Several known blood pressure loci replicated in African Americans and Hispanics. Fourteen variants in three loci (KCNK3, FGF5, ATXN2-SH2B3) were significantly associated with blood pressure in Hispanics. The most significant diastolic blood pressure variant identified in our analysis, rs2586886/KCNK3 (P = 5.2 × 10-9), also replicated in independent Hispanic and European-descent samples. African American and trans-ethnic meta-analysis data identified novel variants in the FGF5, ULK4 and HOXA-EVX1 loci, which have not been previously associated with blood pressure traits. Our identification and independent replication of variants in KCNK3, a gene implicated in primary hyperaldosteronism, as well as a variant in HOTTIP (HOXA-EVX1) suggest that further work to clarify the roles of these genes may be warranted. Overall, our findings suggest that loci identified in European descent populations also contribute to blood pressure variation in diverse populations including Hispanics and African Americans - populations that are understudied for hypertension genetic risk factors.
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U2 - 10.1371/journal.pone.0164132
DO - 10.1371/journal.pone.0164132
M3 - Article
C2 - 27736895
AN - SCOPUS:84991336343
VL - 11
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 10
M1 - e0164132
ER -