Abstract
Epidemiological studies of obesity, Type-2 diabetes (T2D), cardiovascular diseases and several common cancers have revealed an increased risk in Native Hawaiians compared to European- or Asian-Americans living in the Hawaiian islands. However, there remains a gap in our understanding of the genetic factors that affect the health of Native Hawaiians. To fill this gap, we studied the genetic risk factors at both the chromosomal and sub-chromosomal scales using genome-wide SNP array data on ~4,000 Native Hawaiians from the Multiethnic Cohort. We estimated the genomic proportion of Native Hawaiian ancestry (“global ancestry,” which we presumed to be Polynesian in origin), as well as this ancestral component along each chromosome (“local ancestry”) and tested their respective association with binary and quantitative cardiometabolic traits. After attempting to adjust for non-genetic covariates evaluated through questionnaires, we found that per 10% increase in global Polynesian genetic ancestry, there is a respective 8.6%, and 11.0% increase in the odds of being diabetic (P = 1.65×10−4) and having heart failure (P = 2.18×10−4), as well as a 0.059 s.d. increase in BMI (P = 1.04×10−10). When testing the association of local Polynesian ancestry with risk of disease or biomarkers, we identified a chr6 region associated with T2D. This association was driven by an uniquely prevalent variant in Polynesian ancestry individuals. However, we could not replicate this finding in an independent Polynesian cohort from Samoa due to the small sample size of the replication cohort. In conclusion, we showed that Polynesian ancestry, which likely capture both genetic and lifestyle risk factors, is associated with an increased risk of obesity, Type-2 diabetes, and heart failure, and that larger cohorts of Polynesian ancestry individuals will be needed to replicate the putative association on chr6 with T2D.
Highlights
Native Hawaiians are the second fastest growing ethnic group in the U.S, growing 40% from the 2000 to 2010 U.S census [1]
We studied the association of Polynesian genetic ancestry, at genomic and subgenomic scales, with quantitative and binary traits in self-identified Native Hawaiians
We showed that Polynesian ancestry, which likely captures both genetic and non-genetic risk factors related to Native Hawaiian people and culture, is associated with increased risk for obesity, type-2 diabetes, and heart failure
Summary
Native Hawaiians are the second fastest growing ethnic group in the U.S, growing 40% from the 2000 to 2010 U.S census [1]. Native Hawaiians are ~1.7 times more likely to develop cardiovascular diseases than European Americans [8], and cardiometabolic risk factors such as hypertension have been shown to be associated with genealogical estimates of proportion of Native Hawaiian ancestry [9]. Taken together, these observations suggest that in addition to non-genetic risk factors such as lifestyle or diet, there may be systematic differences in the number, frequency, or effect size of genetic risk alleles that contribute to epidemiological differences in disease risks between Native Hawaiians and other continental populations. Such genetic investigation has not been conducted and despite awareness and efforts to include more non-European populations in genomic studies, indigenous populations such as Native Hawaiians remain understudied [10,11,12]
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