Cardio-metabolic disease genetic risk factors among Maori and Pacific Island people in Aotearoa New Zealand: current state of knowledge and future directions.

CONTEXT: Cardio-metabolic conditions in Aotearoa New Zealand (NZ) Maori and non-indigenous Polynesian (Pacific) populations have been increasing in prevalence and severity, especially over the last two decades. OBJECTIVES: To assess knowledge on genetic and non-genetic risk factors for cardio-metabolic disease in the Maori and Pacific populations residing in Aotearoa NZ by a semi-systematic review of the PubMed database. To outline possible future directions in genetic epidemiological research with Maori and Pacific communities. RESULTS: There have been few studies to confirm that risk factors in other populations also associate with cardio-metabolic conditions in Maori and Pacific populations. Such data are important when interventions are considered. Genetic studies have been sporadic, with no genome-wide association studies done. CONCLUSIONS: Biomedical research with Maori and Pacific communities is important to reduce the prevalence and impact of the cardio-metabolic diseases, as precision medicine is implemented in other Aotearoa NZ populations using overseas findings. Genuine engagement with Maori and Pacific communities is needed to ensure positive outcomes for genetic studies, from data collection through to analysis and dissemination. Important is building trust, understanding by researchers of fundamental cultural concepts and implementing protocols that minimise risks and maximise benefits. Approaches that utilise information such as genealogical information and whole genome sequencing technologies will provide new insights into cardio-metabolic conditions-and new interventions for affected individuals and families.

Lack of direct evidence for natural selection at the candidate thrifty gene locus, PPARGC1A.

BACKGROUND: The gene PPARGC1A, in particular the Gly482Ser variant (rs8192678), had been proposed to be subject to natural selection, particularly in recent progenitors of extant Polynesian populations. Reasons include high levels of population differentiation and increased frequencies of the derived type 2 diabetes (T2D) risk 482Ser allele, and association with body mass index (BMI) in a small Tongan population. However, no direct statistical tests for selection have been applied. METHODS: Using a range of Polynesian populations (Tongan, Maori, Samoan) we re-examined evidence for association between Gly482Ser with T2D and BMI as well as gout. Using also Asian, European, and African 1000 Genome Project samples a range of statistical tests for selection (F ST, integrated haplotype score (iHS), cross population extended haplotype homozygosity (XP-EHH), Tajima's D and Fay and Wu's H) were conducted on the PPARGC1A locus. RESULTS: No statistically significant evidence for association between Gly482Ser and any of BMI, T2D or gout was found. Population differentiation (F ST) was smallest between Asian and Pacific populations (New Zealand Maori ≤ 0.35, Samoan ≤ 0.20). When compared to European (New Zealand Maori ≤ 0.40, Samoan ≤ 0.25) or African populations (New Zealand Maori ≤ 0.80, Samoan ≤ 0.66) this differentiation was larger. We did not find any strong evidence for departure from neutral evolution at this locus when applying any of the other statistical tests for selection. However, using the same analytical methods, we found evidence for selection in specific populations at previously identified loci, indicating that lack of selection was the most likely explanation for the lack of evidence of selection in PPARGC1A. CONCLUSION: We conclude that there is no compelling evidence for selection at this locus, and that this gene should not be considered a candidate thrifty gene locus in Pacific populations. High levels of population differentiation at this locus and the reported absence of the derived 482Ser allele in some Melanesian populations, can alternatively be explained by multiple out-of-Africa migrations by ancestral progenitors, and subsequent genetic drift during colonisation of Polynesia. Intermediate 482Ser allele frequencies in extant Western Polynesian populations could therefore be due to recent admixture with Melanesian progenitors.

Indigenous Perspectives and Gene Editing in Aotearoa New Zealand.

Gene editing is arguably the most significant recent addition to the modern biotechnology toolbox, bringing both profoundly challenging and enabling opportunities. From a technical point of view the specificity and relative simplicity of these new tools has broadened the potential applications. However, from an ethical point of view it has re-ignited the debates generated by earlier forms of genetic modification. In New Zealand gene editing is currently considered genetic modification and is subject to approval processes under the Environmental Protection Authority (EPA). This process requires decision makers to take into account Maori perspectives. This article outlines previously articulated Maori perspectives on genetic modification and considers the continuing influence of those cultural and ethical arguments within the new context of gene editing. It also explores the range of ways cultural values might be used to analyse the risks and benefits of gene editing in the Aotearoa New Zealand context. Methods used to obtain these perspectives consisted of (a) review of relevant literature regarding lessons learned from the responses of Maori to genetic modification, (b) interviews of selected 'key Maori informants' and (c) surveys of self-selected individuals from groups with interests in either genetics or environmental management. The outcomes of this pilot study identified that while Maori informants were not categorically opposed to new and emerging gene editing technologies a priori, they suggest a dynamic approach to regulation is required where specific uses or types of uses are approved on a case by case basis. This study demonstrates how the cultural cues that Maori referenced in the genetic modification debate continue to be relevant in the context of gene editing but that further work is required to characterize the strength of various positions across the broader community.

Accounting for Errors in Low Coverage High-Throughput Sequencing Data When Constructing Genetic Maps Using Biparental Outcrossed Populations.

Next-generation sequencing is an efficient method that allows for substantially more markers than previous technologies, providing opportunities for building high-density genetic linkage maps, which facilitate the development of nonmodel species' genomic assemblies and the investigation of their genes. However, constructing genetic maps using data generated via high-throughput sequencing technology (e.g., genotyping-by-sequencing) is complicated by the presence of sequencing errors and genotyping errors resulting from missing parental alleles due to low sequencing depth. If unaccounted for, these errors lead to inflated genetic maps. In addition, map construction in many species is performed using full-sibling family populations derived from the outcrossing of two individuals, where unknown parental phase and varying segregation types further complicate construction. We present a new methodology for modeling low coverage sequencing data in the construction of genetic linkage maps using full-sibling populations of diploid species, implemented in a package called GUSMap. Our model is based on the Lander-Green hidden Markov model but extended to account for errors present in sequencing data. We were able to obtain accurate estimates of the recombination fractions and overall map distance using GUSMap, while most existing mapping packages produced inflated genetic maps in the presence of errors. Our results demonstrate the feasibility of using low coverage sequencing data to produce genetic maps without requiring extensive filtering of potentially erroneous genotypes, provided that the associated errors are correctly accounted for in the model.