Effects of inbreeding, endogamy, genetic admixture, and outbreeding on human health: a (1001 Dalmatians) study.
OBJECTIVE
(1001 Dalmatians) research program collects biomedical information from multiple small isolated populations ((metapopulation)) on Adriatic islands, Croatia, and investigates health effects of human population isolation, inbreeding, admixture, and outbreeding.


METHODS
We collected random samples of 100 individuals from 9 island settlements and an additional sample of 101 immigrants to the islands, pooled from all study populations. According to their personal genetic histories, the examinees were categorized as inbred, autochthonous, admixed, and outbred. A total of 76 inbred individuals from a total sample of 1001 examinees were matched to 76 autochthonous, 76 admixed, and 76 outbred controls by gender, age (+/-5 years), village of residence, education, and socio-economic status. We investigated the effects of presumed individual genome-wide heterozygosity predicted from personal genetic histories on the following 10 traits: systolic and diastolic blood pressure, body mass index, high and low density lipoproteins and total cholesterol, triglycerides, uric acid, creatinine, and blood glucose.


RESULTS
Personal genetic history significantly affected systolic blood pressure (Spearman rho=0.157, P=0.006), while the effect on cholesterol (rho=0.105, P=0.069), and high density lipoprotein cholesterol (rho=0.104, P=0.071) was suggestive. Admixed individuals and immigrants consistently showed values associated with lower health risk. When inbred and autochthonous samples were merged and compared with the admixed and outbred samples to increase the power of the study, the effects on the three traits above and also on body mass index and diastolic blood pressure became statistically significant. The medians for all 10 medically relevant traits in inbred and autochthonous group, with lower values of presumed individual genome-wide heterozygosity, were less favorable in terms of health.


CONCLUSIONS
The combined effects of founder effect, genetic drift, and inbreeding can increase the frequency of detrimental rare variants in human metapopulations, leading to overall worsening of population health, whereas admixture and outbreeding appear to have the opposite effect.
Rudan
Igor
I
Department of Public Health Sciences, Faculty of Medicine, University of Edinburgh, Scotland, UK. irudan@mef.hr
Biloglav
Zrinka
Z
Vorko-Jović
Ariana
A
Kujundzić-Tiljak
Mirjana
M
Stevanović
Ranko
R
Ropac
Darko
D
Puntarić
Dinko
D
Cucević
Branka
B
Salzer
Branka
B
Campbell
Harry
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003241:Consanguinity; D017523:Croatia; D005260:Female; D018703:Founder Effect; D040961:Genetic Drift; D005828:Genetics, Population; D005843:Geography; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D019655:Quantitative Trait, Heritable
D008076:Cholesterol, HDL; D002784:Cholesterol