Despite intensive study, most of the specific genetic factors that contribute to variation in human height remain undiscovered. We conducted a family-based linkage study of height in a unique cohort of very large nuclear families from a founder (Jewish) population. This design allowed for increased power to detect linkage, compared to previous family-based studies. Loci we identified in discovery families could explain an estimated lower bound of 6% of the variance in height in validation families. We showed that these loci are not tagging known common variants associated with height. Rather, we suggest that the observed signals arise from variants with large effects that are rare globally but elevated in frequency in the Jewish population.
Bibliographical noteFunding Information:
Funding was provided by the Howard Hughes Medical Institute (L.K. and D.Ze), https://www.hhmi.org/and the James S. McDonnell Centennial Fellowship in Human Genetics (L.K.), https://www.jsmf.org/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Kruglyak laboratory members for helpful discussion, Eran Segal for lab space and equipment, and the Puah Institute for help in the recruitment of participants.
© 2019 Zeevi et al.