International study of Danes sheds new light on heritable factors in disease multi-morbidities
More precise information about the roles genetics and environment play in determining disease is essential for better understanding and treating both common ailments and killer diseases.
More precise information about the roles genetics and environment play in determining disease is essential for better understanding and treating both common ailments and killer diseases.
An international group of scientists studied detailed health data from 6.3 million Danish individuals over 40 years. Their work produced new results consistent with previous studies but provide more specific information about the role of genetics and environment in disease.
In particular, they analyze the relationship of genetics to co-morbidities, the presence of more than one disease in an individual.
The research appears in a preprint, not yet peer reviewed, in the online medRxiv journal, dated Feb. 10.
The authors write at the outset: "We estimate the heritability and genetic correlation between thousands of disease phenotypes using a novel approach that can be scaled to nationwide data. Our findings confirm the importance of genetics for a number of known associations and increase the resolution of heritability by adding numerous novel associations, some of which point to shared biological origin of different phenotypes."
A detailed view of disease heritability
The size and completeness of the dataset collected from the Danish national health services allowed the researchers to look in great detail at genetics and environmental factors in a large range of diseases and conditions.
They were able to study correlations between diseases, identify disease "pairs," and follow the course of diseases over the long term.
Their data are available to medical and scientific researchers for study and use. Their novel method of analysis, they note, is scalable to large populations.
The researchers found that the highest heritability occurred with "congenital malformations, endocrine diseases and mental disorders." Diseases where genetic components and specific genes were already identified had the highest heritability. These include cystic kidney disease, osteochondrodysplasias (hereditary bone diseases) and congenital malformations.
They also found that shared environment, such as family relationships, contributed to many diseases. "Disregarding environmental components can severely inflate the heritability estimates for many diseases," the researchers write.
New findings and leads for further study
Another finding was that heritability can differ by sex. This occurred in 74 diseases that the team investigated, where generally they found that women had a higher heritability.
Looking at genetic correlations in diseases that had more than 10% heritability, the researchers found two large clusters of mental disorders, one with bipolar disorders, schizophrenia, substance abuse, and hepatitis, and another with childhood and adolescence mental disorders, epilepsy and microcephaly.
The researchers also found an inverse correlation between diabetes and hyperplasia of prostate and Parkinson's disease, which they note might be "due to the protective effects of diabetes medication." Fibromyalgia, they said, had genetic correlations with several diseases, which may help in a better understanding of the ailment.
Some diseases had a "bidirectional relationship," where one disease increased the risk of having another disease. The research team noted that 320 of the disease pairs they identified had a heritability of more than 10%.
"This indicates that often bidirectional relationships represent the same disease, [with an underlying biological process]," they said. Two such bidirectional relationships were recurrent depressive disorder and intestinal disorders, and asthma and GERD.
The researchers identified 1,216 disease pairs which represented "a significantly increased relative risk and directionality occurring in at least 0.1% of the population."
Conclusion
The authors note some of the study limitations. For example they relied on disease coding by individuals in the health system, and there could be coding errors. Also, heritability may change over the years. They stress, however, that their study involved an unusually large population over many years, which may mitigate possible limitations.
Summing up their study, the authors state, "[W]e found a number of novel relationships between specific genetic diseases and subphenotypes such as cleft-palate disease, the trajectories of diabetes diagnoses, and the correlation patterns of mental disease, but we are confident that there are many more discoveries present in this dataset to be cross-referenced or contrasted with known clinical knowledge.
"The results are widely applicable to the design and utility of genome-wide association studies, shared etiology of diseases, and genomic risk prediction, and add to our understanding of the fundamentals of disease development," they concluded.
-----
David Westergaard et al. "Uncovering the Heritable Components of Multimorbidities and Disease Trajectories: A Nationwide Cohort Study." MedRxiv preprint, Feb. 10.
Alerts Sign-up