While most research on common or rare disorders has in the past been conducted in European and East Asian populations, there is increasing interest in conducting such studies in sub-Saharan African populations. There is a growing recognition that health disparity research will be improved by including populations with genetically diverse background. This means we need to include more sub-Saharan Africans in genetic research for common and rare-disorders, especially as this region is known to harbor the greatest amount of genetic variation within our species [1].

Within the United States, minority recruitment for genetic/family studies has been recognized as crucial to understand genetic variation and to enable generalization of research findings. Pharmacogenomic studies, for example, investigate the efficacy of pharmacologic agents in populations with certain genetic characteristics [2–4]. Genetic research in African populations is needed to study the genetic predisposition of Africans to certain diseases. Currently there are projects under way to investigate proposed rheumatoid arthritis loci in African populations [5], to investigate susceptibility of Nigerians to risk loci for chronic kidney disease [6] or to study the effect of certain promoter variants for modulation of serologic autoimmunity to SLE [7].

The Yoruba ethnic group of Nigeria has been sampled in previous genetic studies. The Yorubas were part of the international HapMap studies that led to the sequencing of the Human Genome [8] and to create a map of human genome sequence variations [9]. Samples from the Yoruba ethnic group were also included to collectively identify >3 million common DNA variants, primarily SNPs [10]. SNP data and their linkage disequilibrium patterns provide basic information for genome-wide association studies in African or admixed populations [8, 10–13].

However, to our knowledge there are no genetic studies that use the Nigerian or Yoruba population as their primary target. Our study is in the process of identifying the genetic basis for keloid formation, a wound healing disorder, with the Yoruba ethnic group as the primary target population.

Keloids are scars that grow over the margin of the original injury to the dermis (Figure 1). This often disfiguring, painful, and stigmatizing scar can occur after a minor cut or trauma to healthy skin. Keloids occur mostly in dark pigmented populations [14, 15] including the Yoruba people of Nigeria. There is no good and efficient treatment for keloids [16, 17]. It has been generally accepted that there is a genetic basis for keloids [18–21]. However, the mode of inheritance is still unsettled. Some studies suggest that the keloid inheritance pattern is autosomal dominant [21, 22] while a study of 34 Yoruba family pedigrees (from Nigeria) supported autosomal recessive inheritance [23].

The Yoruba awareness of keloids predates the first publication on keloids in Western literature [24, 25]. According to Omo-Dare, Yorubas for long have referred to keloids in their art and literature [26]. Indeed, one of the 140 chapters in the Ifa literary corpus is dedicated to keloids; with artifacts/sculptures and folklore reflecting keloids. The Yorubas, with their local customs of facial markings and earlobe perforations, recorded their familiarity with keloids 10 centuries before Alibert and Retz [27].

For modern-day genetic research, it is often necessary to recruit thousands of participants, especially for association studies. In the instance of case-control studies, only a single affected participant or a single unaffected control individual per family is recruited. Other strategies involve the recruitment of trios (father, mother, and affected offspring) or sib-pairs. Recruitment for those studies may be relatively straight-forward, although not trivial. For linkage studies, however, large families must be identified where the disorder of interest is transmitted. Challenges arise when many informative family members need to be recruited to give enough power to a pedigree for independent identification of a disease gene locus. Developing strategies to present the research to potential study participants in a manner that enhances voluntary participation of family members from all generations becomes essential, and can be a challenge.

Suggestions to enhance recruitment for genetic/family studies with emphasis on minority recruitment in the US or recruitment in Africa have been addressed in the literature [28–31]. However, literature on recruitment strategies or recruitment experience for genetic/family studies in the Yoruba population is limited. This article documents our recruitment experience for a genetic linkage study in the Yoruba population in Nigeria and describes the challenges we faced as well as methods used to reduce these challenges.

Scientific literature offers several recommendations on ethical, legal and cultural considerations for research in low resource settings and for recruitment of minority populations. Experiences with community engagement and informed consent for genetic studies in Africans [28] and for obtaining DNA samples from four populations including the Yorubas from Ibadan (Nigeria) have also been reported [29]. However, there is no report on issues that should be considered when recruiting entire families in rural and urban settings with genetic research as the main goal.

Successful recruitment of diverse populations such as the Yorubas for genetic studies is important for advancement in biomedical research. The Yoruba ethnic group was chosen for this linkage analysis approach because we were expecting that large families with keloids could be recruited. Due to the expected locus heterogeneity for causative variants leading to keloids [32–34], recruitment from the Yoruba population seemed ideal for finding significant linkage because of relatively low admixture [35, 36] compared to many other populations.

To attain acceptance of a genetic study within multiple generations of a family, it is important to appreciate social, religious, and cultural beliefs that may impact participation. The Yoruba ethnic group that occupies mostly the western part of Nigeria highly values their cultural practices and religious beliefs. Although most Yorubas are Christians or Muslims, they retain their practice of worshiping different gods such as Sango (god of thunder), Obatala also known as Orisa-nla (the shaper, former, maker), Yemoja (god of the river) and Ogun (god of iron). All these beliefs create perceptions about the possible causes for a disease and often determine the approach to treatment. Traditional healers still have high influence on people’s decisions. Part of their health beliefs is that illnesses may originate from one or a combination of three forces; the magical practices (witches or sorcerers), natural events (environmental, hereditary) and supernatural occurrence (destiny or the individual’s double spirits) [37–39]. It has also been documented that many Nigerians approach treatment of diseases by utilizing Western medicine in combination with treatments offered by traditional healers and “spiritual” centers [37].

For example, one study reported that some Yorubas identified environmental factors such as diet and use of unorthodox traditional herbs as the cause for cancer [38]. The interest in experimenting with different treatments could explain why some of the participants in our keloid study reported treatment of their keloids with a combination of traditional herbs and Western medicine and why they were willing to contribute to science to find better treatment or cure. However, stigmatizing and/or painful diseases such as cleft lip and palate, cancer or keloids are by some perceived to be in part due to a “punishment” for evil deeds or result from retaliation by a jealous foe [37, 38, 40]. As a result, many Nigerians are weary of participating in studies that have the potential of “affecting” them or other family members, especially if they donate blood, saliva or hair samples. Recruitment was also affected by challenges that had already been described in other cultural environments [30, 41]. Such issues included economic factors, lack of trust, different cultural background of researchers and study participants, or issues with time and transportation needed to reach remotely located family members.

Meeting regulatory and administrative requirements (IRB, ethics committees and FWA) as well as staff training was less of a problem compared to recruitment challenges. Research staff took the Collaborative Institutional Training Initiative (CITI) training for good clinical practice before they engaged in recruitment. An online education module for ethics training on research based on the Nigerian Code for Health Research Ethics has recently been developed and validated. Future studies will require research staff to take this module that encompasses the Nigerian cultural and social principles [42].

Our experience with this study confirmed the need to allocate extra time for all stages of the study. Extra time was needed to educate the public and prospective research participants about the study and to make up for delays due to travel logistics when recruiting relatives residing outside a proband’s home town or when family members were not available for recruitment in a timely manner. Additional challenges arose during the rainy season when treacherous road conditions led to extended delays. Unreliable public transport slowed down recruitment throughout the study period. While purchasing a car dedicated to the study might have been the most economical way to travel to recruitment sites, administrative barriers and uncertain liability issues prevented us from doing so.

Working with an institution with established research infrastructure versus a site without any research infrastructure or experience with foreign collaboration should be taken into consideration when planning a study as this will likely impact timely study initiation, staff recruitment, and research coordination. There is recognition that capacity building in African countries must be addressed for successful integration of human genetic studies [43]. Nigerians and specifically the Yorubas are generally not research-naïve. Participation of Yorubas or any underserved population in genetic studies can be enhanced by community involvement from inception of the study as well as by regular feedback [30], especially when the study design involves participation of family members from several generations. Our study plan included the assistance from probands or other individuals with keloids and contact with community leaders, kings or chiefs where applicable. Interaction with members of the oldest generation or children of old family members may be difficult when the culture of scientists and recruiters is different from that of the participants. To address these and other issues, our study involved research staff from the local community who were born and raised in the Yoruba culture. Visits to kings, chiefs, churches and mosques were useful to convince the community that blood and saliva samples would not be used for voodoo or juju. It was important and reassuring to be accompanied by research participants from their community at such meetings to demonstrate that nothing bad had happened to them since recruitment. It was also important to ensure that clinic or hospital administrators were aware of this study so that they could then encourage the population to participate. We were allowed to recruit in local palaces, churches and health centers/hospitals. Additionally, the research staff was available for recruiting during special holidays when relatives would return home for family celebrations. Cultural sensitivity during study coordination was ensured by a member of the US team that was born and raised in the Yoruba community.

Genetic analysis identified non-blood relatives in some families. Some pedigrees had to be updated several times as additional information became available. While scientists require accurate information about a participant’s position in a family it is more important for the traditional Yoruba family where individuals fit within a family than how they are biologically related. When obtaining family histories, we found that “adopted” distant relatives were sometimes identified as children or parents. We also encountered situations where friends of the family were reported as members of the family. These situations required that research staff approached a certain member of the family with clear questions to obtain accurate information before establishing a pedigree. During DNA analysis we still identified participants who did not fit in the family structure. The need for confidentiality in these situations was discussed among researchers and participants were either removed from the pedigree or in rare instances the family was eliminated from analysis. With increasing education, the community may become more aware of inheritance and biological relationships within a family and better understand the significance of genetic family studies. Until then, investigators should be prepared to address these factors in their study plan.

Even though remuneration is always a difficult topic for recruitment in low resource settings, it is still an incentive for participants who otherwise may not be able to travel to a recruitment site or miss some work/earning to volunteer for a study “without immediate benefit” to them. Other studies also reported that some participants expected more payment for their contribution [29], while others preferred to have free treatment/cure in lieu of money [44]. Investigators should be aware of the potential for abuse by opportunists that may impact recruitment. Our research protocol, for example, required that all study participants be treated and compensated equally.

In a review of Project SuGar, the author identified some dynamics that negatively affected recruitment of African-American families into genetic studies and offered suggestions to enhance recruitment [30]. Impacting factors included economic barriers, core values including cultural, spiritual and social factors, as well as health practices of the community. Previous studies have demonstrated that the majority of Nigerians would participate in research activities. Several approaches have been recommended or used to engage, recruit and retain Nigerians for genetic studies [45]. Such methods include the use of community advisory councils, incentives, local partners/champions, focus groups, awareness through public forums and less cumbersome wording during the informed consent process. Our study employed many of these suggestions.

Knowledge of genetic variations and their roles in disease pathology and for treatment outcome is significant in the quest to reduce health disparities. While there seems to be a recent increase in genetic studies conducted in African countries, the majority is usually in collaboration with and led by Western scientists. African countries must continue to be involved and take a leadership role in genetic studies so their people can benefit from the advances of the genomic and the post-genomic era. One could argue that the Yoruba people still have to offer a lot to science. Nigerians have been called upon to embrace the opportunity of improving their people’s quality of life with a timely response to technology gaps in genomics [46]. Initiatives such as the MalariaGen [47] and the Human Heredity and Health in Africa (H3Africa) project, among others, have begun to address this concern (H3Africa: Human heredity and Health in Africa, http://www.h3africa.org/).

We believe that our recruitment experience amongst the Yorubas in Nigeria will be useful to other researchers who plan similar large genetic study studies in Africa or in other low resource settings. We have identified administrative and cultural differences as well as challenges due to insufficient infrastructure that can lead to delays in successful recruitment. As other genetic multigenerational studies are undertaken in low resource settings, investigators will recognize that a combination of methods that address the issues outlined in this article can enhance the success of their studies.