HARVARD MEDICAL SCHOOL
Circles in Human Evolution: Genetics of Areola Diversity
Dr. Cliff Tabin, PhD
Dr. Abigail Wark, PhD
CONSENT TO PARTICIPATE IN RESEARCH
The age of personalized genomics offers an unprecedented chance to understand the biology of uniquely human traits. One interesting and understudied human-specific trait is the areola, a circle of specialized, pigmented skin surrounding the human nipple. Areolas have been proposed to play an intriguing role in human evolution and human health; differences in areola morphology have been linked to sexual selection, nursing behavior, and infant weight gain. Developmentally, circular markings have a simple genetic architecture, making the areola both an interesting and a practical case study into the genetic underpinnings of distinctively human traits.
The Tabin Laboratory at Harvard Medical School invites both men and women to help us learn about the causes and consequences of diversity in the human areola.
What is this document?
This document provides information that will allow you to give informed consent to participate in this research project. Please read the following information carefully. This consent form discusses activities and risks associated with the current study. You should ask Dr. Abigail Wark, or her representative, to explain any sections that are unclear to you and to answer any questions that you have. You should not sign this form unless you understand what is written in this form and have had your questions answered to your satisfaction. You are encouraged to discuss the information with family and friends. If, after deciding to participate in this study, you find you have more questions, you should contact Dr. Abigail Wark, whose contact information is available at the end of this form. If you decide to participate in this study, please keep a copy of this consent form for your records as it contains important information, including names and telephone numbers that you may wish to have in the future.
What is the purpose of the study?
The goals of our study are to 1) provide the world’s first detailed characterization of the morphological diversity of the areola, and 2) to identify the genes responsible for variation in the appearance and glandular structure of the areola.
Although mammary glands and nipples are found in all mammals, pigmented areolas are found only in humans. We do not know why humans have these circular markings. Some researchers have suggested that they play a role in mate selection, potentially indicating fertility. Others think the may serve as visual targets to help nursing human infants locate breast milk. While we do not know why we have areolas, we do know that areolas are diverse and that this diversity has consequences. For example, the areola contains unique glands that provide an attractive signal to newborn human infants. Women differ in the number of these glands contained in the areola and infants whose mothers have more glands have been reported to gain weight more quickly in the first few days after birth. This difference in gland number is just one example of the type of diversity we observe in the human areola. Areolas can also vary in size, shape, color, etc. The aim of this study is to characterize all externally visible aspects of the areola and to discover the genes that determine the appearance and structure of this uniquely human trait.
The study will have to following tangible outcomes: 1) improve our understanding of the human areola and of human biological diversity, 2) identify genes that contribute to human morphological variation, and 3) generate testable hypotheses about connections between the areola and breast feeding, breast disease and human evolution.
What are the procedures to the followed?
This study is non-invasive and is expected to take approximately one hour. Participation will occur at the participant’s home using a measurement kit and an online survey. First, participants will be asked to fill out an online survey about health factors that could influence areola appearance, including weight, parity and breastfeeding history, hormonal status, etc. Next, participants will be asked to perform a breast and areola self-characterization wherein they will take measurements and photographs of their areolas (self-characterization can be performed at home). Photographs are an important but optional part of the study. Measurements and images will be uploaded to our secure server for analysis. Trait data will be aligned with genomic data (when available) for association mapping and other genetic analyses. All results will be reported at the conclusion of the study. We plan to enroll approximately 2000 people in the study.
What are the risks of participation?
o Health risks:
Exposure to adhesive tape: Participants in this study will have their skin briefly exposed to adhesive tape. Any participants who have known reactions to adhesive materials (or whose potential reaction is unknown) should use the ID sticker labels with appropriate caution.
o Privacy and Confidentiality
Risk of unintended viewers: Throughout the study period, every effort will be made to ensure that your study data will not be viewed by unintended viewers. When you join our study, you will be assigned a study identification number. The survey we send you (and the data we collect from it) will be connected to your study ID number but will not contain your name or mailing address. These steps prevent the study team or an unintended viewer from being able to connect your trait data to your personal identifying information. However participants must accept the risk of a breech of confidentiality. All survey data will be collected via a third party server. While the third party has agreed to keep the data confidential, Harvard does not control the security of that server. In addition, federal funding and regulatory agencies may have the right to review the records from this study to be sure that certain rules are followed correctly. Therefore it is important that participants understand the risk a breech of confidentiality could mean that photographs or other data could be viewed by unintended viewers.
Risk that data could be connected to you: This study will not intentially associate the identity of participants with trait or genetic data. However, we do intend to link participants’ trait data to their available genetic data. The identifiable nature of genetic data (especially whole genome sequence data) means that it is possible that participants will be identified. Therefore privacy cannot be guaranteed and we cannot offer promises of anonymity or confidentiality. Participants who make their genome information public are reminded about the possibility that their genomic, health, medical and other data will not only be made public but may be publicly identified, by name. The participants should also remember that learning about their own genome implicates their family members to various degree, and the participants should consult with their family before choosing whether to participate in genome-related research.
Participants are welcome to publish their survey data, photographic data, or genome data at their own discretion. If they choose to do this, the connection between their genetic and trait data becomes their personal responsibility and rests in their control. Participants may also choose not to publish their trait data publically, or they may choose to publish a portion of the data (for example numerical but not photographic data). Please note that this does not guarantee the anonymity of trait data due to the possibility of unintended viewership or genetic reidentification (described above).
Survey entries, measurements and photographs collected in the current study will be used for the research purposes described in this document. Because scientific communication and publication are a standard component of academic research, any of the data collected (including photographs) may be shown in scientific communications. This data, like all data in the study, will remain coded and we will not associate this data with participants’ name, address, or other identifying information. However, the public nature of the PGP genome data makes it possible that published data could be connected to an individual’s identity. This is a risk inherent in the publication of genome information.
o Risks pertaining to potential findings:
Participants should consider the potential implications of the findings from the current study. The purpose of the study is to catalog variation in breast and areola morphology among human patients and to map genetic loci associated with these traits. Some of the potential findings of the study include the finding that certain populations and ethnic groups differ in these traits or in the genetic loci associated with them or that some aspect of breast or areola morphology may be indicator of underlying disease, such as breast cancer.
What are the benefits of participation?
Individual benefits: No direct benefits will come to you from participating in this study. This study does not provide treatment of any kind. You will not receive any information about your personal health or disease risks. This study is not intended to lead to the development of a commercial product. In the event that a commercial product is developed, there are no plans to provide financial compensation to the participant.
Societal benefits: This study will provide new information about human biological diversity and about the morphology of the human areola. This information will help the biomedical community gain a better understanding of individual morphological and genetic variation. In addition, we hope that this study will improve our understanding of healthy breast biology and will pave the way for a more personalized approach to breast health and disease.
How can I withdraw from the study?
You may decide not to participate in the study at any time. In the case of withdrawal, the participants data will be withdrawn from all further analyses whenever possible. The decision to withdraw from this study will not result in the loss of any benefits to which you would otherwise be entitled. Note that removal of study data from a participant’s study profile page (for example, their Open Humans or PGP page) may not be sufficient to ensure that you are removed from the study. Thus please notify Dr. Abigail Wark if you would like to be withdrawn from the study.
Participants may be asked to leave the study at the discretion of the research team in the following circumstances: to ensure their safety or for failure to comply with the study protocol.
Are there any costs associated with the study?
The participant is not expected to incur any costs associated with the current study.
Is there a stipend?
There is no stipend associated with this study.
What should I do in the event of a research-related injury?
If you are physically injured as a result or your participation in this study, please seek medical care immediately and contact the Project Director. Harvard’s policy is not to provide compensation for medical treatment and your insurance carrier may be billed for the cost of such treatment. In making medical treatment available, or providing it, the persons conducting this research project are not admitting that your injury was their fault.
The following contact information must be provided to research participants:
For answers to questions about the research or to voice concern or complaint about the research, or to report a study-related problem or injury: Abigail Wark, PhD, Project Director, Harvard Medical School, email@example.com, 617 432 6530.
For questions, problems, concerns or complaints about the study, or for information about your rights as a research participant: Carolyn M. Connelly, PhD, Director, Office of Research Subject Protection, Harvard Medical and Dental Schools, 617 432 0651.
I certify that I am the intended recipient of this informed consent document.
I have read (or had read to me) this consent form. I have been given the opportunity to ask questions and my questions were answered to my satisfaction.
I understand that I may refuse to participate in this study and that if I refuse to participate, this will not result in the loss of any benefits or services to which I am otherwise entitled. I agree to participate in this study. I also understand that if, for any reason, I wish to stop participating, I will be free to do so, and this will have no effect on my future care or services. I may print a copy of this consent form for my records.