This study analyzed the whole-genome data of 347,000 individuals of European descent, providing the first comprehensive quantification of genetic contributions to 34 complex traits and diseases. It found that genes explain about 88% of the "missing heritability," with common variants contributing 78% and rare variants 22%. Notably, rare variants in non-coding regions were found to play a key role in regulating health, contributing 79% of the heritability from rare variants. The research highlights the significant influence of genetics on health and disease, while also emphasizing the substantial impact of lifestyle factors on traits like body weight, advancing personalized medicine and precision prevention.
Have you ever wondered why some people can eat whatever they want without gaining weight, while others seem to gain weight just by drinking cold water? Why do some people grow to be over six feet tall while others constantly look up at them? Is this a result of "genetic manipulation" behind the scenes, or the subtle influence of environmental factors?
With the rapid development of precision medicine and genome sequencing technologies, we are gradually uncovering the deep impact of genetic factors on human health and traits. According to statistics, more than 400 million people worldwide suffer from diabetes, nearly 2 billion adults are overweight or obese, and cardiovascular diseases are consistently ranked as leading causes of death. To what extent are these common diseases and complex traits "destined" by our genetics?
Recently, a groundbreaking research paper titled "Estimation and Mapping of the Missing Heritability of Human Phenotypes," published in the prestigious journal Nature, may have provided one of the closest answers to this age-old question. This study, led by scientists from Queensland University in Australia, and others, reveals critical insights from a large-scale genomic study involving 350,000 individuals.
350,000 Genomes: The First Comprehensive Quantification of "Genetic Influence"
In this study, researchers analyzed the whole-genome data of 347,000 individuals of European descent from the UK Biobank. They systematically assessed the genetic contribution of 34 complex traits and diseases, including height, weight, cholesterol levels, hypertension, fertility, smoking behavior, heart disease, and more. The study not only confirmed the significant role of genes in individual differences but also conducted the first systematic evaluation of rare non-coding variants, previously considered "genetic dark matter," which traditional research methods could not reach.
The core breakthrough of this study lies in filling the gap of "missing heritability." For a long time, there has been a discrepancy between estimates of heritability based on family pedigree studies and the genetic contributions identified through traditional genetic testing. This study shows that whole-genome sequencing can explain approximately 88% of pedigree-based heritability, with the remaining 12% potentially attributed to ultra-rare variants, structural variations, or non-additive genetic effects.
The Distribution of Genetic Contributions: A Clear Breakdown
Specifically, the sources of genetic inheritance show a clear division: common variants (minor allele frequency, MAF ≥ 1%) contributed about 78%, while rare variants (MAF < 1%) contributed about 22%. This finding challenges the traditional belief that "only common variants matter." Even more surprising is that among the rare genetic variants, non-coding regions account for 79%, while coding regions contribute only 21%. These non-coding regions, once considered "genetic deserts," actually hold the key to regulating health. The study also found that the genetic enrichment effect in coding regions is significant: common variants in coding regions are 36 times more enriched, and rare variants are 26 times more enriched, meaning that while coding regions make up a smaller proportion of the genome, they have a stronger regulatory influence on traits.
Differences in Heritability Across Traits
The study also revealed varying genetic contributions to different traits:
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Height has the highest heritability at 70.9%, making it the trait most "controlled" by genetics.
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BMI (Body Mass Index) has a heritability of 33.9%, much lower than the previously estimated 50% based on pedigree studies. This suggests that lifestyle factors such as diet and exercise play a much larger role in weight than previously thought.
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Fertility (number of children) has a heritability of only 7.5%, meaning it is almost entirely shaped by environmental and personal choices.
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Lipid-related traits (such as LDL and HDL cholesterol) were found to have a significant association with rare genetic variants, explaining over 25% of the heritability for rare variants. This could pave the way for targeted prevention of cardiovascular diseases.
Heritability estimation of 34 complex traits and diseases
34 Traits and Diseases Fully Explained by Genomic Data
Notably, the heritability of 15 quantitative traits (such as hemoglobin concentration and platelet count) was entirely explained by the whole-genome data, indicating that we now have near-complete understanding of the genetic foundations of these traits. Through Genome-Wide Association Studies (GWAS), the research team identified 12,129 independent trait-associated loci, including 886 rare variant associations, providing a solid foundation for fine-mapping disease-causing genes.
From "Fortune-Telling" to "Disease Prevention": The Age of Genomics Is Here
Professor Loïc Yengo, one of the lead researchers, emphasized that the next step is to identify which specific genetic variants are responsible for the development of diseases in some individuals while others remain healthy. This could help us identify high-risk individuals before diseases manifest, enabling early preventive measures. Furthermore, large-scale genomic databases, such as the UK Biobank, are becoming "gold mines" for advancing personalized medicine.
This research not only answers the long-standing question of "how important are genes" but also provides a more refined "human genetic map." It shows us that:
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Genes indeed play a significant role in shaping part of our fate, especially regarding traits like height and cholesterol levels.
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However, we are not entirely bound by our DNA—lifestyle and environmental choices still give us the power to rewrite our health scripts.
Perhaps in the near future, each individual will have their own "genetic instruction manual," guiding us on how to eat, exercise, and live in ways best suited to our unique genetic makeup. Until then, don't forget: you still have the power to co-write your own health story!