Journal article
Genome-wide association and population genetic analysis of C-reactive protein in African American and Hispanic American women
American journal of human genetics, Vol.91(3), pp.502-512
09/07/2012
DOI: 10.1016/j.ajhg.2012.07.023
PMCID: PMC3511984
PMID: 22939635
Abstract
C-reactive protein (CRP) is a systemic inflammation marker that predicts future cardiovascular risk. CRP levels are higher in African Americans and Hispanic Americans than in European Americans, but the genetic determinants of CRP in these admixed United States minority populations are largely unknown. We performed genome-wide association studies (GWASs) of 8,280 African American (AA) and 3,548 Hispanic American (HA) postmenopausal women from the Women's Health Initiative SNP Health Association Resource. We discovered and validated a CRP-associated variant of triggering receptors expressed by myeloid cells 2 (TREM2) in chromosomal region 6p21 (p = 10(-10)). The TREM2 variant associated with higher CRP is common in Africa but rare in other ancestral populations. In AA women, the CRP region in 1q23 contained a strong admixture association signal (p = 10(-17)), which appears to be related to several independent CRP-associated alleles; the strongest of these is present only in African ancestral populations and is associated with higher CRP. Of the other genomic loci previously associated with CRP through GWASs of European populations, most loci (LEPR, IL1RN, IL6R, GCKR, NLRP3, HNF1A, HNF4A, and APOC1) showed consistent patterns of association with CRP in AA and HA women. In summary, we have identified a common TREM2 variant associated with CRP in United States minority populations. The genetic architecture underlying the CRP phenotype in AA women is complex and involves genetic variants shared across populations, as well as variants specific to populations of African descent.
Details
- Title: Subtitle
- Genome-wide association and population genetic analysis of C-reactive protein in African American and Hispanic American women
- Creators
- Alex P Reiner - Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. apreiner@u.washington.eduSandra BelezaNora FranceschiniPaul L AuerJennifer G RobinsonCharles KooperbergUlrike PetersHua Tang
- Resource Type
- Journal article
- Publication Details
- American journal of human genetics, Vol.91(3), pp.502-512
- Publisher
- United States
- DOI
- 10.1016/j.ajhg.2012.07.023
- PMID
- 22939635
- PMCID
- PMC3511984
- ISSN
- 1537-6605
- eISSN
- 1537-6605
- Grant note
- HHSN268201100002I / NHLBI NIH HHS HHSN271201100004C / NIA NIH HHS HHSN268201100046C / PHS HHS HHSN268201100001C / WHI NIH HHS HHSN268201100004I / NHLBI NIH HHS P30 CA015704 / NCI NIH HHS HHSN271201100004C / PHS HHS HHSN268201100003C / PHS HHS HHSN268201100004C / WHI NIH HHS HHSN268201100046C / NHLBI NIH HHS HHSN268201100002C / WHI NIH HHS HHSN268201100001I / NHLBI NIH HHS HHSN268201100004C / PHS HHS HHSN268201100002C / PHS HHS HHSN268201100003C / WHI NIH HHS HHSN268201100001C / PHS HHS
- Language
- English
- Date published
- 09/07/2012
- Academic Unit
- Epidemiology; Internal Medicine
- Record Identifier
- 9983995167202771
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