Comparing Genetic and Socioenvironmental Contributions to Ethnic Differences in C-Reactive Protein

Abstract

C-reactive protein (CRP) is a routinely measured blood biomarker for inflammation. Elevated levels of circulating CRP are associated with response to infection, risk for a number of complex common diseases, and psychosocial stress. The objective of this study was to compare the contributions of genetic ancestry, socioenvironmental factors, and inflammation-related health conditions to ethnic differences in C-reactive protein levels. We used multivariable regression to compare CRP blood serum levels between Black and White ethnic groups from the United Kingdom Biobank (UKBB) prospective cohort study. CRP serum levels are significantly associated with ethnicity in an age and sex adjusted model. Study participants who identify as Black have higher average CRP than those who identify as White, CRP increases with age, and females have higher average CRP than males. Ethnicity and sex show a significant interaction effect on CRP. Black females have higher average CRP levels than White females, whereas White males have higher average CRP than Black males. Significant associations between CRP, ethnicity, and genetic ancestry are almost completely attenuated in a fully adjusted model that includes socioenvironmental factors and inflammation-related health conditions. BMI, smoking, and socioeconomic deprivation all have high relative effects on CRP. These results indicate that socioenvironmental factors contribute more to CRP ethnic differences than genetics. Differences in CRP are associated with ethnic disparities for a number of chronic diseases, including type 2 diabetes, essential hypertension, sarcoidosis, and lupus erythematosus. Our results indicate that ethnic differences in CRP are linked to both socioenvironmental factors and numerous ethnic health disparities.

Relative impact of genetic ancestry and neighborhood socioeconomic status on all-cause mortality in self-identified African Americans

“…A growing number of multilevel studies have examined African ancestry as a predictor of chronic disease endpoints [ 20 , 21 , 36 , 46 , 63 – 67 ]. Geographic analyses of migration patterns in the US have shown that genetic admixture patterns in present-day African Americans are associated with forced movements of people that occurred during the trans-Atlantic slave trade [ 23 , 24 ].…”

“…When adopting a social sciences theory of health disparities, scientists estimating causal effects of genetic ancestry on health outcomes should control for variables assumed to be consequences of historical systematic racism, discrimination, and segregation to avoid conflating genetic ancestry effects with these other correlates of SIRE. A growing number of multilevel studies have examined African ancestry as a predictor of chronic disease endpoints [20,21,36,46,[63][64][65][66][67]. Geographic analyses of migration patterns in the US have shown that genetic admixture patterns in present-day African Americans are associated with forced movements of people that occurred during the trans-Atlantic slave trade [23,24].…”

“…Both biomedical and social scientists acknowledge that relying on SIRE or perceived race/ ethnicity to infer causality is problematic due to its high correlation with several interrelated biologic and non-biologic pathways that drive disparities [13,[16][17][18]. Acknowledging the poor specificity of SIRE to understand causes of disparities, scientists have turned to genetic ancestry as a measure of the biological contribution to racial disparities in health [19][20][21]. Remarkable diversity in genetic ancestry exists, even among members within the same SIRE group [22][23][24].…”

What's Race Got to Do With It? CRP Levels in Immune Mediated Skin Diseases: Considerations for Hidradenitis Suppurativa

“…revealed higher serum levels of inflammation-mediated C-reactive protein (CRP) in UK populations composed largely of older, Black females. Notably, the sample included only 6,456 (0.1%) Black subjects and 426,842 (98.5%) White subjects ( 4 ). Compared to census demographics reported during the same time period (2006-2011), this sampled population underrepresents Black communities ( 3 ).…”

Rye: genetic ancestry inference at biobank scale

“…UKBB participants' genome-wide genotypes were characterized using the UKBB Axiom Array or United Kingdom BiLEVE Array as previously described (23,30). UKBB participant genomewide genotypes were merged and harmonized with genomic variant data from global reference populations characterized as part of the 1KGP ( 26) and the Human Genome Diversity Project (HGDP) (31) as previously described (32,33). Reference populations were grouped into seven regional ancestry groups based on their genetic and geographic affinity.…”