Denmark’s “intermediate” FH-FDB prevalence is somewhere between regions with full founder effect and melting pots such as Germany and the USA

Founder effect leads to unusual prevalence rates. So the fact that a founder effect is present in a region would preclude using that region as a proxy for a prevalence estimate of the general population.

FH is genetically heterogeneous, and in Denmark the mutational spectrum is intermediate, with APOB and LDLR mutations accounting for the majority of mutations, and in particular three mutations in the LDLR gene accounting for 36% of known LDLR mutations in FH patients (12, 13). ~ Familial Hypercholesterolemia in the Danish General Population: Prevalence, Coronary Artery Disease, and Cholesterol-Lowering Medication: Marianne Benn, Gerald F. Watts, Anne Tybjaerg-Hansen,and Børge G. Nordestgaard J Clin Endocrin Metab. First published ahead of print August 14, 2012 as doi:10.1210/jc.2012-1563

Here, Jensen, et al, reported that the Danes were somewhere between outright founder effect and those considered fully heterogeneous.

The Danish spectrum of 29 different mutations, five of which account for almost half of heterozygous FH, is intermediate between that of countries such as South Africa, where three mutations cause 95% of heterozygous FH in the Afrikaners, and Germany or England, where there are many more mutations. ~ Spectrum of LDL receptor gene mutations in Denmark: Implications for molecular diagnostic strategy in heterozygous familial hypercholesterolemia, November 1999, DOI: 10.1016/S0021-9150(99)00158-6 · Source: PubMed, H.K. Jensen, et al.

The above is expanded upon later in the paper. Denmark is somewhere in the middle of outright Founder Effect and a heterogeneous population.

Across nations, the spectrum of LDL receptor gene mutations is rather complex (Fig. 2). In populations such as Christian Lebanese [26], Ashkenazi and Sephardic Jews [27,28], Druze Arabs [29], South African Afrikaners [11], French-Canadians [30], Icelanders [31], and Finns [32], a few mutations predominate due to founder effects. In countries as Japan [33], Germany [34] or England [10,12], many more mutations produce a highly heterogeneous picture. The Danish spectrum of 29 different mutations, five of which account for almost half of heterozygous FH, the spectra seen in Norway [35] and Greece [36] are intermediate between the above mentioned populations. ~ Spectrum of LDL receptor gene mutations in Denmark: Implications for molecular diagnostic strategy in heterozygous familial hypercholesterolemia, November 1999, DOI: 10.1016/S0021-9150(99)00158-6 Source: PubMed, H.K. Jensen, et al. ·

The population study in Denmark in the Northern/central European region where the APOB defect originated. It is well documented that this area has a higher prevalence than external areas.

Thus, most countries appear to have cohorts within the general population with increased prevalence of FH due to relatively few mutations that no doubt reflect a history of cultural and/or geographic isolation. The latter include Denmark with five mutations occurring in 50% of FH patients and Tunisia with a FH prevalence of about 1 in 165. ~ “Familial hypercholesterolemia: epidemiology, Neolithic origins and modern geographic distribution,” Khemanganee, et al.