The impact of global and local Polynesian genetic ancestry on complex traits in Native Hawaiians

Autor: Lynne R. Wilkens, Iona Cheng, Hanxiao Sun, Loic Le Marchand, Lifestyle Samoan Obesity, Christopher A. Haiman, Emily M. Russell, Ryan L. Minster, Annette Lum-Jones, Charleston W. K. Chiang, Meng Lin, Bryan L Dinh, Muagututia Sefuiva Reupena, Take Naseri, Tsz Fung Chan
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
Cancer Research
Multifactorial Inheritance
Native Hawaiian or Other Pacific Islander
Physiology
common
Samoa
Disease
QH426-470
Cardiovascular Medicine
Body Mass Index
Cohort Studies
0302 clinical medicine
Medical Conditions
Risk Factors
Native Hawaiians
Epidemiology
Medicine and Health Sciences
Ethnicities
Genetics (clinical)
Oligonucleotide Array Sequence Analysis
0303 health sciences
common.demographic_type
Genomics
Phenotype
Adipose Tissue
Physiological Parameters
Connective Tissue
Cardiovascular Diseases
030220 oncology & carcinogenesis
Cohort
Female
Anatomy
SNP array
Research Article
medicine.medical_specialty
Genetic genealogy
Cardiology
Biology
Polymorphism
Single Nucleotide
Hawaii
White People
03 medical and health sciences
medicine
Genetics
Humans
Genetic Predisposition to Disease
Obesity
Molecular Biology
Life Style
Ecology
Evolution
Behavior and Systematics
030304 developmental biology
Heart Failure
Asian
Polynesian People
Body Weight
Austronesian People
Biology and Life Sciences
Cardiovascular Disease Risk
medicine.disease
Biological Tissue
Diabetes Mellitus
Type 2
People and Places
Genetics of Disease
Population Groupings
Body mass index
Demography
Genome-Wide Association Study
Zdroj: PLoS Genetics
PLoS Genetics, Vol 17, Iss 2, p e1009273 (2021)
ISSN: 1553-7404
1553-7390
Popis: 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.
Author summary Native Hawaiians are one of the fastest growing ethnic minorities in the U.S., and exhibit increased risk for metabolic and cardiovascular diseases. However, they are generally understudied, especially from a genetic perspective. To fill this gap, 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. While we do not endorse utilizing genetic information to supplant current standards of defining community membership through self-identity or genealogical records, our results suggest future studies could identify population-specific genetic susceptibility factors that may elucidate underlying biological mechanisms and reducing the disparity in disease risks in Polynesian populations.
Databáze: OpenAIRE
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