Paradies Yin C, Montoya Michael J, Fullerton Stephanie M
Menzies School of Health Research, Institute of Advanced Studies, Charles Darwin University, Casuarina NT, Australia.
Perspect Biol Med. 2007 Spring;50(2):203-27. doi: 10.1353/pbm.2007.0020.
Current debate on the use of population genetic data for complex disease research is driven by the laudable goals of disease prevention and harm reduction for all, especially dispossessed, formerly enslaved, or colonized populations. This article examines one of the oldest gene-based theories of complex disease causation: the thrifty genotype hypothesis (THG). This hypothesis is emblematic of the way in which genetic research into complex disease attracts a high investment of scientific resources while contributing little to our capacity to understand these diseases and perpetuating problematic conceptions of human variation. Although there are compelling reasons to regard the high prevalence of type 2 diabetes mellitus as a by-product of our biological incapacity to cope with modern affluent and sedentary lifestyles, there is at present no consistent evidence to suggest that minority populations are especially genetically susceptible. Nor is it clear why such genetic differences would be expected, given the original pan-species orientation of the TGH. The limitations inherent in current applications of the TGH demonstrate that genetic research into complex disease demands careful attention to key environmental, social, and genetic risk factors operating within and between groups, not the simplistic attribution of between-group differences to racialized genetics. A robust interdisciplinary approach to genetic epidemiological research is proposed.
当前关于将群体遗传数据用于复杂疾病研究的争论，是由为所有人，尤其是被剥夺权利者、曾经被奴役者或被殖民群体预防疾病和减少伤害这一值得称赞的目标所推动的。本文探讨了最古老的基于基因的复杂疾病病因理论之一：节俭基因型假说（THG）。这一假说体现了复杂疾病的基因研究吸引大量科学资源投入，却对我们理解这些疾病的能力贡献甚微，且使关于人类变异的问题观念长期存在的方式。尽管有令人信服的理由将2型糖尿病的高发病率视为我们在生物学上无法应对现代富裕和久坐不动生活方式的副产品，但目前尚无一致证据表明少数群体在遗传上特别易患该病。考虑到THG最初的泛物种取向，也不清楚为何会预期存在这种基因差异。THG当前应用中固有的局限性表明，复杂疾病的基因研究需要仔细关注群体内部和群体之间起作用的关键环境、社会和基因风险因素，而不是将群体间差异简单归因于种族化的基因。本文提出了一种强大的遗传流行病学研究跨学科方法。
